Search results for “Stem”

Apomorphine Subcutaneous Infusion is More Efficient Than foslevodopa/foscarbidopa Subcutaneous Infusion in the Treatment of Advanced Parkison´s Disease for the Spanish National Health System

Objectives Motor fluctuations and non-motor disorders not manageable by first-line treatments in advanced Parkinson's disease require continuous dopaminergic stimulation strategies such as subcutaneous infusions of apomorphine (APO) or foslevodopa/foscarbidopa (FLD/FCD). A Budget Impact Analysis (BIA) was performed to estimate the cost difference between both treatments assuming equivalent clinical efficacy and safety. Material and methods The efficacy results of pivotal clinical trials at 12 and 52 weeks of treatment and the safety profile of APO vs FLD/FCD were compared, based on latest scientific publications and other available clinical data. A comparative BIA was performed, based on estimated annual drug treatment costs at Spanish published prices. Results The efficacy of APO (16 h/day) and FLD/FCD (24 h/day) in reduction of OFF hours (2.47 vs 2.75, 12 weeks; 3.66 vs 3.50, 52 weeks; respectively) and increase of ON hours without disabling dyskinesias (2.77 vs 2.72, 12 weeks; 3.31 vs 3.80, 52 weeks; respectively) could be considered clinically equivalent, as well as their safety profiles. However, a significant discrepancy is observed in the costs of the aforementioned alternatives. Considering published prices and the average dose reported in the literature, in Spain the annual cost of APO would be €13,980 compared to €55,198 for FLD/FCD. Consequently, the financial resources required for the treatment of FLD/FCD would enable the treatment of approximately three to four patients with APO. The BIA indicated the potential for annual savings in more than €2,500 million, considering a total target population of over 60,000 patients per year. Finally, an univariant sensitivity analysis was performed, considering a scenario in which the hospital acquisition cost of FLD/FCD decreased between 20%-30% (€44,159- €38,638/year). In this scenario, the total annual savings range between €1,875-€1,532 million per year. Conclusions Overall APO is more efficient than FLD/FCD, as it provides similar clinical efficacy at a lower treatment cost. The selection of an appropriate treatment option is to be determined by clinical criteria and patient characteristics, but cost evaluation should be considered to select the most cost-effective therapeutic option.

A Solar Water Heater Using a Two-Stage Thermostat as a Pre-Heating System for a Feed Plant

Solar thermal heating is a mature technology for producing hot water in the domestic sector. Industrial processes require significant heat, so solar water heaters can be used for pre-heating. A forced- circulation solar water heater is installed in a feed plant that is located south of the Tropic of Cancer. The thermal efficiency of the system is closely related to the incident solar radiation. This study uses a two-stage setting for a thermostat to collect more solar energy if incident solar radiation is less intense. When the temperature difference between the water storage tank and the water outlet for the solar collectors (setting of a thermostat from 6° to 8°C) increases, there are more energy savings. The simple payback period for the system is 2.05 years, so it is financially viable to use a solar water heater for industrial heat processes. Excessive carbon emissions resulting from industry processes are a main cause of global warming. Carbon tax can be used as a central climate policy instrument for carbon reduction. The government of Taiwan stipulates the legal foundation for levying carbon fees in 2025. The carbon emissions and carbon tax for the feed plant are described to prompt the case for sustainability.

Diabetic Mouse Delayed Wound Model Following Treatment with the NerveStim™ Neuropathy System

Delayed wound healing in diabetes is characterized by impaired angiogenesis, persistent inflammation, extracellular matrix dysregulation, and peripheral neuropathy. A preclinical study was conducted using a diabetic mouse delayed wound model to evaluate the surrounding tissue of a wound, (its periwound) and its tissue responses following treatment with the NerveStim™ Neuropathy System, a combination topical gel and neuromuscular electrical stimulation platform. Periwound tissue was harvested at Day 14 and analyzed using NanoString gene expression profiling. Treated animals demonstrated visibly increased periwound tissue thickness compared to untreated controls. Differential expression analysis identified 76 significantly upregulated and 17 downregulated genes. Upregulated pathways included angiogenesis (Vegfa, Fgf2, Pdgfb, Nos3), neurotrophic signaling (Ngf, Bdnf, Scn9a, Trpv1), macrophage polarization (Arg1, Mrc1, Il10), and extracellular matrix remodeling (Col1a1, Col3a1, Mmp9, Timp1). Downregulation of select pro-inflammatory mediators (Nos2, Mif) was observed. These coordinated transcriptional changes are consistent with activation of reparative immune, neurovascular, and matrix remodeling pathways in diabetic periwound tissue.

Integrating Analgesic Doses and Pain Trend Analysis: A Novel Clinical Support System

Background Prescribing appropriate analgesics with optimal dosages based on patients' pain severity is challenging, especially when multiple painkillers are involved. Tracking and analyzing the effectiveness of analgesics and their dosages over time is crucial for pain management. Existing systems lack the ability to integrate analgesic equivalent doses with temporal trends in pain scores, hindering effective decision-making. Methods We developed a Clinical Support System that calculates the daily oral morphine equivalent dose and analyzes trends in consumed equivalent doses of analgesics. The system provides a graphical user interface that displays medication prescriptions, actual medication usage, and pain scores. It offers features such as correlating analgesic drug usage with pain intensity, trend analysis of analgesic drug usage and pain intensity, and identification of effective oral morphine equivalent doses. Results The system overcomes previous barriers in drug analysis by providing real-time calculation of oral morphine equivalents and trend analysis of pain duration. It assists physicians in prescribing appropriate and safe medication dosages, enhancing medication safety for patients. Conclusions Our clinical support system offers a comprehensive solution for analyzing trends in consumed equivalent doses of analgesics. It integrates medication prescriptions, actual usage, and pain scores, providing decision-making support for pain management.

Systematic Review on Peri-Operative Intravenous Fluid: ‘Restrictive vs Liberal’ Fluid use on Major Abdominal Surgical Patients

Background Intravenous Fluids use during surgery is a common practice for many reasons. However recent evaluation of perioperative abdominal surgery patients have poised many issues. Mostly on the type of fluid and quantity of volume usage on major abdominal surgery. Many studies into this aspect of perioperative fluid usage have been done, and volume definition have been accrued either restrictive (Maintenance fluid of less than 1.75 Liters) or liberal or standard (Maintenance fluid between 1.75 Liters to 2.75 Liters) usage. The outcome was assessed to ascertain the best patient recovery without complications from the two fluid regime. Result/Discussion After PRISMA exclusion criteria, there were eight randomized control studies assessed to provide a summary, comparing all the studies using either restrictive fluid or liberal fluids used in major abdominal surgery. Post operative complications and the length of hospital stay were assessed as the major outcomes end points and the cumulative result favored those with restrictive fluid usage. Conclusion Although the restrictive use of fluids in abdominal surgery is favored from the measured outcomes, there are inherent cofounders and heterogenicity in the eight studies that require more detail studies involving multiple study centers and population.

The Energy–Matter–Behavioral Model of Mental Health Hygiene: A Systems-Based Framework for Sustainable Well-Being

The Energy–Matter–Behavioral (EMB) model offers a systems-based lens for understanding and maintaining mental health hygiene. This framework integrates stress reduction, biological resilience, and behavioral reinforcement into a coherent triad, addressing not only symptoms but underlying energetic and material dynamics. By aligning practices such as exercise, meditation, social connection, sleep, and diet with EMB principles, this model presents a transdisciplinary, evidence-informed approach to mental health in an overstimulated world.

Monitoring of Insect Species Richness and Abundance in Sudan Semi-arid Ecosystem (Case study: Khartoum State/Sudan)

Sudan's ecological landscape is characterized by various zones, including deserts, semi-deserts, and savannas, which host a diverse array of forests, rangelands, and numerous plant and animal species. However, the sustainable management of these resources is becoming increasingly challenging due to human activities and the impacts of climate change. This article presents the results of a research project focused on monitoring and documenting biodiversity in Sudan's semi-arid regions, particularly emphasizing insect diversity. Insects are vital for maintaining ecosystem health through processes such as nutrient cycling, decomposition, pollination, and acting as natural predators to pests. Field surveys were conducted across three Sudanese states—North Kordofan, Gezira, and Khartoum—to assess the diversity of flora and fauna. Specifically, El Rawakeeb semi-arid land in Khartoum state was investigated, which comprised three sites with varying soil elevations: a hilly site at 420 meters above sea level, a flat site at 416 meters, and a valley site at 411 meters. Researchers utilized direct collection methods and butterfly nets to gather insect specimens, which were subsequently preserved and identified for further analysis. Diversity indices, including Simpson’s Diversity Index, Shannon-Wiener Index, and Margalef Richness Index, were computed to compare the biodiversity of these sites, along with metrics for evenness and species richness. Permanova analysis was carried out for insect variation between the study sites. A total of 1541 insect specimens were gathered from El Rawakeeb, encompassing 34 species distributed across 21 families and 9 orders. The order Lepidoptera exhibited the greatest number of species (35.29%), followed by Coleoptera (20.59%). The orders Neuroptera, Orthoptera and Thysanoptera recorded the fewest species (2.94% each). From the hilly site, 514 insect specimens were collected, representing 9 orders, among which Hymenoptera included 4 species, while Lepidoptera had 3 species, and Odonata, Orthoptera, and Thysanoptera each had 1 species. The highest individual counts were recorded for Copriniklobe (dung beetle), Dacus longistylus (fruit fly), Camponotussp. (carpenter ant), and Anax ephippiger (dragonfly). In a flat site, 484 insect specimens were collected, classified into 15 species, 12 families, and 7 orders. The highest individual counts were noted in four species: Onthophagusnuba (dung beetle), Dacus longistylus (fruit fly), Camponotussp. (carpenter ant), and Anax ephippiger (dragonfly). In a valley site, 543 insect specimens were collected, categorized into 17 species, 16 families, and 9 orders. Insect Diversity in three research sites. Simpson's Diversity Index revealed varying levels of insect diversity across the three sites. The valley site exhibited the highest diversity level with an index score of 0.857, followed by the flat site at 0.826, and the hilly site at 0.819. The Shannon diversity index of 2.22 indicated the highest diversity among the three sites, suggesting a relatively diverse insect community. The relative abundance of insects was greatest in the valley site at 35.24%, followed by the hilly site at 33.35%, and the flat site at 31.41%. The Margalef Richness Index indicated a moderate level of richness in the insects collected from the three locations. Certain insect species were found in some sites but were absent in others. The PERMANOVA revealed notable variations among the three study sites (F = 2.24, p-value = 0.035).

Systematic Review of Spinal Cord Injuries in Equestrian Athletes: Incidence, Risk Factors, and Outcomes

Objective The goal of this systematic review is to identify common themes amongst acute spinal cord injuries (SCI) in equestrian athletes. Design A systematic review was performed using PubMed, CINAHL Plus with Full Text (EBSCO), Cochrane Library, and Scopus with pre-determined MESH terms. The initial search returned 354 studies. Following PRISMA guidelines, 13 articles were included. Exclusion criteria included injuries to the horse only, non-English language, cauda equina, and case reports. Data extraction was completed, and common findings were evaluated narratively due to heterogeneity of data. Results Seven manuscripts listed specific horse-related activities that caused SCI, with fall from horse as the highest percentage of injury. Nine articles identified the injury region, with large variations and no clear dominant area of injury. Five articles identified the length of hospital stay with ranges from 1 to 82 days. Four articles looked at the association of professional vs non-professional riders. Only two articles evaluated helmet use at time of injury, with one article showing 81% of those with SCI used helmets, and the other showing only 35.6% utilized this safety measure. Conclusion SCI in equestrian athletes can have a wide presentation, with large variation on location of injury, length of stay, and other factors. However, non-professional riders are at greater risk of SCI and individuals are more likely to sustain injury from a fall from a horse rather than a kick or another modality of injury. Future study can elicit presenting symptoms, types of surgical intervention used, and long-term outcomes and recovery.

The Brainstem Auditory Evoked Potential: A Reinterpretation of its Electrogenesis

Depending upon the species, the brainstem auditory evoked potential (BAEP) consists of four or five major high frequency components. According to longstanding doctrine, each wave represents the sequential activation of successively higher nuclei and tracts from the 8th (auditory) nerve to the midbrain (inferior colliculus). Although this conceptual framework has acquired the status of near dogma, surprisingly little evidence exists in support. In the present analysis, a new interpretation of the electrogenesis of the BAEP is proposed which is simpler although it retains skeletal elements of the older explanation. The revised model is mostly derived from two distinct sources. In the first, the timing of the BAEP waves is compared with that of cortical activity for a range of mammals including humans, monkeys, cats, rats and guinea pigs. It is demonstrated that for each of these, the conduction time of the acoustic signal to the cortex from the putative midbrain component (wave IV or V) is so unrealistically long that it implies that the entire waveform must arise in the peripheral pathways of the auditory system. In the second, a retrospective analysis is made of click repetition rates on the BAEP using extradural electrodes. It was shown that at high rates of stimulation (about 100/sec), the behavior of the waveform is almost totally at variance with the expectations of the conventional model. The essence of the revised conception is that all BAEP waves are just variations of the compound action potential of the 8th nerve, albeit generated or regenerated via separate routes and different methods. Such an explanation would thereby account for their near uniform sharp morphology as well as creating the impression of a composite neuronal response. More specifically, in the case of a four component BAEP, wave I is assumed to be generated by the normal air conduction route in an identical manner to the conventional explanation. In contrast, wave ll is assumed to be generated via bone conduction in the temporal skull thereby bypassing the transduction process in the middle ear. Wave lll is assumed to be generated by the first echo of the bone-conducted sound wave. Likewise, the second rebound within the temporal bone serves as the stimulation to evoke wave lV. As the energy of the auditory stimulus gradually dissipates, it may still continue to generate a train of lower amplitude potentials. It is concluded that the BAEP may contain little or no brainstem or midbrain activity and therefore the term BAEP may be a misnomer. A more appropriate epithet might therefore be the auditory nerve evoked potential or ANEP.

Bridging Gaps in Blood Transfusion Services through Collaborative Healthcare Systems in Cameroon: The Cornerstone University Blood Management System version 1.0

The rising need for structured and efficient blood transfusion services in low-resource settings has driven the adoption of collaborative blood transfusion management systems (CBTMS). This study explores the functionality and impact of the Cornerstone University Blood Management System version 1.0 (CUBMS vs 1.0) in Cameroon. This study was an exploratory research design which used a system interface analysis, comparative case reviews from four countries, and literature synthesis, to reveal that CUBMS improves accessibility, data management, inventory control, emergency responsiveness, and community engagement. Despite infrastructural challenges in rural regions, the system can enhance efficiency, transparency, and safety in blood services. The success of CBTMS in Cameroon is linked to digital infrastructure, training, and culturally relevant community engagement. The Ministry of Public Health of Cameroon should prioritize the nationwide implementation of CBTMS, ensuring consistency in digital health tools.

Factors Influencing HIV Status Disclosure Among People Living with HIV/AIDS in Mukono District, Uganda: Beyond Health System Support

Background HIV status disclosure is a complex process influenced by multiple factors beyond health system support. Understanding these factors is essential for developing comprehensive interventions to promote disclosure and improve HIV prevention and care outcomes. Methods A descriptive cross-sectional study was conducted in 10 health facilities offering comprehensive HIV/AIDS care in Mukono district, Uganda. Data was collected from 317 clients through interview-guided questionnaires. Data was entered using EPI data and analyzed using SPSS version 16, including logistic regression to identify factors associated with disclosure. Results Multiple factors influenced HIV status disclosure. Individual factors included knowledge about HIV (OR=2.34, 95% CI: 1.45-3.78), self-efficacy (OR=3.12, 95% CI: 1.87-5.21), and psychological readiness (OR=2.89, 95% CI: 1.76-4.75). Relationship factors included relationship quality (OR=3.56, 95% CI: 2.13-5.94), communication patterns (OR=2.78, 95% CI: 1.65-4.69), and anticipated partner reaction (OR=4.23, 95% CI: 2.54-7.05). Community factors included perceived stigma (OR=0.34, 95% CI: 0.21-0.56), cultural norms (OR=0.45, 95% CI: 0.27-0.75), and religious beliefs (OR=1.87, 95% CI: 1.12-3.14). Structural factors included economic dependence (OR=0.38, 95% CI: 0.23-0.63) and access to support services (OR=2.45, 95% CI: 1.47-4.08). Conclusions HIV status disclosure is influenced by a complex interplay of individual, relationship, community, and structural factors. Effective interventions to promote disclosure must address these multiple levels of influence, going beyond health system support to create enabling environments for disclosure at the individual, relationship, community, and structural levels.

Ecosystem-Based Fishery Management of Antarctic Krill (Euphausia superba) to Support Baleen Whales and other Predators Production Adapted for Potential Climate Change Effects

Antarctic krill is an important component of the zooplankton production in the Southern Ocean and is a major food source for baleen whales. The role of commercial fishing and predation by whales on Krill abundance has been investigated here using the innovative ecosystem-based fishery management, EBFM which maintains the krill to whale food web ecosystem stability. The literature indicates the Krill fishery may have been overfished, so it was reduced to the current annual upper limit of 0.62 million tonnes for support other predators of krill, such as seals, penguins and flying sea birds. However, recent literature suggests a moderate reduction in krill catch in the Antarctic Peninsula area due to its importance for whale migration to temperate areas. The Peninsula area catch was estimated to be reduced by about 10% due to additional concerns about climate change effects on krill abundance in the Southern Ocean, reducing overall catch to 0.556 million tonnes, moderately higher than the maximum taken in 2022. Hence, the krill biomass fishing was reduced to allow for predation by baleen whales and other predators, giving a full ecosystem-based fishing mortality similar to that previously estimated to maintain krill production in the Southern Ocean.

Health Practitioner Burnout, Safety Implications, and Programmatic Fixes: A Systematic Literature Review of Current Literature Reviews—200 Proof*

High rates of workplace psychological stress and burnout have been chronic among Healthcare Practitioners. Research shows that Healthcare Practitioner psychological stress / burnout is related to poor quality of care and a high probability of making medical errors and mishaps resulting in harm to patients and even workers themselves. In response, relatively impactful programs have been developed to address Practitioner burnout. To derive a better understanding of the subject and inform best practices and policy regarding the problem and its fixes, this article reports findings from a novel study of a systematic (PRISMA-based) literature review of current (circa ~10 years <) literature reviews; or a distillation of reviews already at 100 proof then undergoing a further distillation into a review of 200 proof.* This study employed a grounded theoretic qualitative methodology to iteratively generate and enumerate descriptive themes from the study’s literature review articles. This article reports on what is currently known regarding the precipitants of Health Practitioner Burnout, Burnout itself, its relationship to Safety lapses and mishaps, and Programmatic Interventions (i.e., Fixes). The primary conclusion is that Health Practitioners are the foundation of healthcare organizations and key to quality care and management / leadership should be concerned for their wellbeing; and this article provides a general blueprint in terms of addressing burnout and safety. Study Limitations and Future research are also discussed.

Why Do Human Body Systems Go Into Catastrophic System Failure Leading to Diseases -Is the Answer in Science or Nature?

Both the human body and the natural world are governed by multiple complex systems. These systems have feedback loops which is a process in which the outputs of a system are circled back and used as inputs. Where there are multiple systems, there is always the potential for a catastrophic system failure. If a system fails in the human body, this can lead to a number of life-threatening and debilitating diseases such as cancer. Diseases such as cancer is in effect, the result of a catastrophic system failure. There are cancer cases in which the root cause of the disease is unknown. System failure in the human reproductive system can lead to congenital birth defects. In cases of a system failure leading to congenital birth defects, some of the causal factors are known but in 65% of these cases, the reasons for this reproductive system failure are unexplained. There are neurological diseases such as Parkinson’s, multiple sclerosis and Alzheimer’s where again, the root causes are unknown. Then there are a number of infectious diseases where the root cause is unknown. The initial causative factors for most of these human diseases are well known. What has yet to be fully understood is the primary root cause that triggers and underpins these system failures in the first place. Nature also has devastating system failures such as in earthquakes and hurricanes. Humans and nature are a close partnership and nature can influence human health. Nature’s systems are deeply interconnected and often exhibit complex behaviours due to positive and negative feedback loops present in both nature and human body systems. Using systems methodology and systems thinking and philosophical insights, the objective is to try to ascertain the answer as to why there are these unknown root causes of diseases; questions that presently, science alone cannot explain. It will be argued that as man and nature are as one, the answers as to why human body systems fail leading to disease may lie not in science but in nature.

Ethics of Modern Stem Cell Research and Therapy: Current Critical and Interdisciplinary Perspectives

From an academic and clinical point of view, stem cell therapy represents one of the most promising advances in modern medicine, with the ability to partially induce the regeneration of acutely injured or chronically damaged tissues. Stem cell research provides new opportunities for the treatment of various conditions, among them diabetes mellitus, HIV, cardiovascular diseases, and neurodegenerative illnesses. Stem cell therapy is currently not FDA-approved in the US (except for certain blood cancers). While bioethics and religion have mostly discussed the source of cells, i.e., embryonic cells that require the destruction of embryos versus adult tissue for research purposes, we also discuss the controversies with regard to currently offered therapies, and marketing of unapproved procedures from a scientific, clinical, and religious viewpoint.

A Systematic Review of Dengue Fever and Dengue-Associated Neurological Conditions Was Conducted in an Attempt to Better Understand This Disease

Dengue is a global arbovirus disease primarily carried by Aedes aegypti and Aedes albopictus mosquitoes. It has four serotypes (DENV1, DENV2, DENV3, and DENV4) and is classified into distinct genotypes. The epidemic is complicated by immunological interactions and viral lineage turnover. Neurological problems are commonly associated with DENV2 and DENV3, with DENV2 displaying the most severe symptoms. Direct viral invasion, host-mediated immune system reactions, or host-mediated metabolic alterations can all result in dengue-related neurological issues. The three dengue vaccinations and the significance of meta-analyses for genetic data will also be covered. Finally, establish a connection with the microRNAs associated with dengue fever, creating new opportunities for the creation of dengue treatment regimens involving microRNAs.

Automated Grassweed Detection in Wheat Cropping System: Current Techniques and Future Scope

Wheat is a staple grain crop in the United States and around the world. Weed infestation, particularly grass weeds, poses significant challenges to wheat production, competing for resources and reducing grain yield and quality. Effective weed management practices, including early identification and targeted herbicide application are essential to avoid economic losses. Recent advancements in unmanned aerial vehicles (UAVs) and artificial intelligence (AI), offer promising solutions for early weed detection and management, improving efficiency and reducing negative environment impact. The integration of robotics and information technology has enabled the development of automated weed detection systems, reducing the reliance on manual scouting and intervention. Various sensors in conjunction with proximal and remote sensing techniques have the capability to capture detailed information about crop and weed characteristics. Additionally, multi-spectral and hyperspectral sensors have proven highly effective in weed vs crop detection, enabling early intervention and precise weed management. The data from various sensors consecutively processed with the help of machine learning and deep learning models (DL), notably Convolutional Neural Networks (CNNs) method have shown superior performance in handling large datasets, extracting intricate features, and achieving high accuracy in weed classification at various growth stages in numerous crops. However, the application of deep learning models in grass weed detection for wheat crops remains underexplored, presenting an opportunity for further research and innovation. In this review we underscore the potential of automated grass weed detection systems in enhancing weed management practices in wheat cropping systems. Future research should focus on refining existing techniques, comparing ML and DL models for accuracy and efficiency, and integrating UAV-based mapping with AI algorithms for proactive weed control strategies. By harnessing the power of AI and machine learning, automated weed detection holds the key to sustainable and efficient weed management in wheat cropping systems.

RETRACTED: Leap into Fetal Surgery; In Utero Placental Mesenchymal Stem Cell Therapy, A Contemporary Approach to Treating Myelomeningocele

This article has been retracted on April 10, 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2997-2086.jfs-25-5857) Myelomeningocele (MMC), a class of spina bifida is a type of neural tube defect. According to the U.S. Centers for Disease Control and Prevention, each year approximately 1,400 babies born in the United States have spina bifida. The disease manifests with the lack of skin and bone covering the caudal part of the spinal cord. The patient developing such a condition often develops lifelong impaired lower limb mobility accompanied by hydrocephalus, and urinary and bowel incontinence. The available interventions include prenatal and postnatal surgery to fuse the dura. Prenatal surgery performed before 26 weeks of gestation reduces the risk of death or the need for ventriculoperitoneal shunting. It also enhanced results on a comprehensive index for mental and motor function. When compared to postnatal surgery, prenatal surgery reduces the manifestation of several secondary outcomes, including the degree of hindbrain herniation seen in the Chiari II malformation. Stem cell therapy for MMC on animal models of chick, ovine, and rodents with reported cases 15/63, 15, and 136, respectively, using human Embryonic Stem Cells (hESCs), Neural Stem Cells (NSCs), Mesenchymal Stem Cells (MSCs) showed significant coverage of MMC defect and slight neurogenesis was also observed. With an understanding of medical literature about in-utero regenerative capacity, it is to be appreciated that placental stem cells surgically seeded within a biocompatible scaffold of the cell patches can play a part in alleviating the spinal cord manifestation associated with MMC. Documented animal studies show that incorporating Placental Mesenchymal Stem Cells in prenatal surgery has reported improved neurogenesis and lower limb mobility. In an ovine myelomeningocele model, the development of in-utero myelomeningocele repair with human Placental Mesenchymal Stem Cells seeded onto an extracellular matrix (PMSC-ECM) enhances motor findings. The clinical trial for the first stem cell therapy on human subjects known as the “CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele.” is expected to be finished by 2030. So far, the cases undergoing treatment have shown significant leg movement and a greater degree of bowel and urinary control. This FDA-approved clinical trial is envisioned to be the future of treating MMC.

Retraction Note: Leap into Fetal Surgery; In Utero Placental Mesenchymal Stem Cell Therapy, A Contemporary Approach to Treating Myelomeningocele

Exploring the Endocannabinoid System: From Circadian Rhythms to Sleep Regulation and Potential Therapeutic Insights

A state‑of‑the‑science review links the endocannabinoid system to circadian regulation and sleep physiology, examining therapeutic prospects and research gaps.

The Effects of Dairy Consumption on Vaccine Immune Response and Immunoglobulins: A Systematic Literature Review

Public health interest in vaccinations and immune protection has increased with the COVID-19 pandemic. Dairy products are an important source of protein and other nutrients, and there are unresolved research questions regarding the potential health impact of dairy products on the enhancement of immune response. A systematic literature review was conducted to synthesize the published literature reporting the effects of dairy interventions on: 1) the vaccine-specific immune response and 2) immunoglobulins in the absence of vaccination. To assess study validity and quality, we used the Academy of Nutrition and Dietetics Quality Criteria Checklist. Sixty-one studies (59 clinical trials, 1 cohort, 1 cross-sectional survey) were included, spanning 1983-2017. Ten trials evaluated the effect of dairy intervention on vaccine-specific IgG, IgA, IgM, vaccine-specific antibody titers, seroprotection rates, or seroconversion rates. Of these, 7 reported significant increases with dairy interventions for post-vaccine tetanus antibodies, mean change in tetanus antibody level, total antibody titers to flagellin from Salmonella Adelaide, mean antibody titers to influenza B, influenza-specific IgA and IgG levels, and seroconversion or seroprotection rates for influenza A and B. Fifty-six studies evaluated dairy’s effects on immunoglobulins without vaccinations. The results were heterogenous, with some studies reporting significant enhancement of immunoglobulins (IgA, IgE, or IgG), while others observed no differences between groups. Clinical relevance of the immunoglobulin changes was not investigated in these studies. Dairy products and their components could enhance the efficacy of vaccines. This review highlights the evidence gaps and provides a potential roadmap for additional research.

The Role of Non-Pharmacological Interventions for Disrupted Sleep in the Moderate-Severe Dementia Population: A Systematic Review

This study systematically reviews the literature on non-pharmacological interventions for disrupted sleep-in people meeting established criteria for moderate-severe dementia, and to analyze the methodological quality of the included studies. The PubMed, PEDro, Cochrane, Virtual Health Library, APA PsycInfo databases were searched using a systematic literature review approach to identify various types of non-pharmacological treatments that improve disrupted sleep-in subjects with moderate-severe dementia. In accordance with the inclusion criteria, eight studies were systematically reviewed and analyzed according to the type of non-pharmacological treatment carried out. This systematic review showed that 50% of the studies used bright light therapy, 12.5% ​​the use of manual therapy, and 37.5% sleep hygiene or walking or a combination of these interventions. Based on the results of the present study, although there is some evidence to support these strategies, it is not significantly supported and highlights variation in the way the interventions were delivered. Disrupted sleep is highly prevalent in people with dementia and have a negative impact on the quality of life of the sufferer and the caregiver. Non-pharmacological approaches to its treatment are increasingly popular as an alternative to drugs, whose efficacy and side effects have raised concerns among the population. Currently, there is a need to carry out more future research to establish its effectiveness and to be able to provide clear guidelines at the time of clinical practice.

A Review on Response of Root System Architecture and Root Phenotypic for Biotic And Abiotic Stress

Root is has great role for plant adaptation and productivity of the agricultural crops as well as other plants by exploiting the soil resource thus, important for plant growth and development or main growth factors. Root system architecture is made up of structural features which exhibits great role in response to environmental stress, and critical to plant growth and development with sufficient root growth. Root system architecture has a central role in crop plants’ response to abiotic (soil microorganisms) and abiotic stresses like water stress, mechanical impedance. Root morphology can be affected by nutrient availability, osmotic stress, salinity, and light. Phenotyping root is one of the drought management tools as roots are more prone to drought conditions and play a significant role in the plant’s life by extracting soil resources from deeper soil layers to carry on several metabolic functions in the plant’s body and its phenotyping helps to understand different root traits. Understanding interactions between roots and their surrounding soil environment is important to increase root growth, which can be improved through root phenotyping. In addition, knowing of the development and architecture of roots, as well its plasticity, holds thus great role for stabilizing the productivity under suboptimal conditions in the root environment

Stemming The Tide Of Hypertension In Women: Optimal Age For Obstetric Debut

Objective Women have continued to bear a heavy burden of cardiovascular disease morbidity and mortality with hypertension as the flagship. This is partly because as the modifiable cardiovascular disease risk factors are falling in rate, gender specific risk factors have persisted. One of them is age at first pregnancy and delivery. Methods In order to contribute to this discourse, we secondarily analysed data generated in a previous field study on risk factors for cardiovascular diseases in free living adults in Plateau State, Nigeria. The women were divided into four groups and we looked at blood pressure at the time of study from the perspective of age at first pregnancy. Reults It was found that those who had their first pregnancy in the late teenage years had the lowest mean arterial blood pressure many years down the line; better than those who started child bearing earlier and those who started later. There was also significant within and between group differences in the blood pressures (p = 0.000). Conclusion To stem the tide of female hypertension later in life, child bearing should not start in the early teenage years nor be unnecessarily delayed. Sociocultural conditions that promote early teenage marriage and pregnancy should be discouraged.

The trajectory of immunoglobulins immune response against the different amounts of xenobiotics matches the trajectory of biological changes associated with ageing: A systematic review

Background Ageing is a life process in which progressive molecular, cellular, physiological and anatomical changes manifesting in humans and animals including other organisms lead to the decline of biological functions. Immunoglobulins (Igs) are glycoprotein molecules produced by white blood cells mainly B lymphocytes following signal transduction as a result of their interaction with pathogenic microbes or poisonous substances introduced into the body systems. They elicit responses against the side effects of pathogens and poisons in which their response efficiency usually declines as we are ageing. Objective Thus, the similarities between Igs’ immune response against the different amounts of xenobiotics and the biological changes associated with ageing have been systematically assessed using the reports of different study results on humans and animals. Methods First, a literature search was carried out in google, PubMed and google scholar using planned search terms related to the title of this study. Review and original articles were retrieved, downloaded and saved on a computer. And then the effects of different factors i.e. xenobiotics, age, sex and lifestyle-based practices on the levels of serum Igs (IgG, IgA and IgM) in animals and humans have been studied using a systematic review of different literature sources. Finally, the relationship between the findings of various studies has been assessed and judgment on the possible cause of ageing has been made. Results The findings of different research have demonstrated that the signaling efficiency of immunoglobulin M (IgM) has been limited by the amount of test compounds administered to study Balb c mice in the oral route. The response efficiency of IgM immune response against the lower doses of test compounds were high compared to the higher doses of test compounds which was low. The results of different other studies also demonstrated that the decline of serum IgM levels was associated with ageing. The relationship between alcohol consumption and the concentration of serum Igs was also described in the report of different studies. These studies have shown that there was lower level of IgG in the blood serum of alcohol consumers compared to non-consumers. The study has also demonstrated a lower level of serum IgM with higher alcohol consumption and higher serum concentration with moderate beer consumption. Conclusion The trajectory of Igs’ immune response against different amounts of xenobiotics was highly associated with the trajectory of biological changes during ageing. These research findings might be the possible evidence to conclude that ageing is caused by the foodstuffs and non-foodstuffs we usually consume, the lifestyles we usually experience and the way of life we usually live in the environment which gradually defiling the natural processes of the body.

Effect of Extracts of Dialium guineense Stem Bark on Lipid Profile and CCl4- Induced Histological Changes in Liver of Wistar Rats

The present study investigated the effect of aqueous and ethanol extracts of Dialiumguineense stem bark on lipid profile and CCl4- induced histological changes in liver of Wistar rats. Adult male Wistar rats (n = 25) weighing 160 – 180 g (mean weight = 170 ± 10 g) were randomly assigned to five groups (5 rats per group): normal control, CCl4 control, silymarin, aqueous extract and ethanol extract groups. With the exception of normal control, the rats were exposed to CCl4 (single oral dose of 1.0 mL/kg body weight, bwt). Silymarin group rats were administered standard hepatoprotective drug, silymarin, at a dose of 100 mg/kg bwt, while those in the two treatment groups received 1000 mg/kg bwt of aqueous or ethanol extract orally for 28 days. Lipid profile parameters were determined in plasma, while rat liver was subjected to histopathological examination. The results showed that the levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), very-low density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) as well as atherogenic index of plasma (AIP) were significantly lower in CCl4 control group than in normal control group, but they were increased by extract treatment (p < 0.05). However, there were no significant differences in atherogenic coefficient (AC) and cardiac risk ratio (CRR) among the groups (p > 0.05). Carbon tetrachloride (CCl4) markedly disrupted the structure of hepatocytes and induced steatosis (intra-hepatocyte fat in-growth and inflammation) which was predominantly microvesicular. However, treatment with aqueous and ethanol extracts of D. guineense stem bark showed marked regeneration of hepatocytes (unremarkable hepatic lobular architecture). The toxic hepatic injury induced by CCl4 was significantly blocked by the plant extracts.

Computational Systemic Biology for Toxicity Studies: A Mini Review of Previously Published Articles

The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.

Evaluation of A Nutrition Feeding Algorithm for Children and Adolescents Undergoing Haematopoietic Stem Cell Transplantation (HSCT)

Background Nutrition support during the acute phase post allogeneic haematopoietic stem cell transplantation (HSCT) is required to optimise short- and long-term outcomes for children. An algorithm was developed and evaluated to assist clinicians to make objective and consistent enteral feeding decisions. Methods The algorithm was evaluated on all patients who underwent allogeneic HSCT treatment between November 2017 - February 2019. Results Of the 48 patients, 43 had a nasogastric tube (NGT) inserted, of which 36 patients received a hydrolysed peptide-based formula, 5 patients received a whole protein formula only and 2 patients were fed an amino acid-based formula. Parenteral nutrition (PN) was used in 41 of the patients. Eleven did not have an NGT in-situ at the commencement of HSCT. Of the remaining 37 patients, 26 followed the algorithm and 11 patients did not comply. The group of patients who did not follow the algorithm had the longest median length of stay (LOS) of 49 days. Patients receiving only EN had the lowest median LOS of 30 days. The two groups that reported better weight outcomes were those who followed the algorithm and those who were fully EN fed. Conclusions Effective use of the HSCT feeding algorithm indicated improved patient outcomes for children undergoing HSCT, with better weight outcomes and reduced LOS. Recommendations to improve the efficacy and compliance of the algorithm include regular education/input to the oncology medical teams to better understand objective thresholds for EN and PN commencement.

A Cancer Theory: The Central Nervous System’s Adaptive Changes Make Chronic Diseases Incurable

We examined special roles of the Central Nervous System (CNS) in an attempt to resolve the puzzle that chronic diseases cannot be cured in medicine. By exploring a skill-learning model, we found that the CNS is able to remember certain information reflecting biochemical and cellular (B&C) processes in the body. From the skill-using ability, we found that the CNS is able to control basic B&C processes that drive and power the skill. From the ability to adjust forces and moving direction of body parts, we infer that the CNS is able to adjust B&C processes that control physical acts. From this controlling capability, we inferred that the CNS must also store certain information on the baseline B&C processes, is able to up-regulate or down-regulate the B&C processes, and make comparisons in performing its regulatory functions. We found that chronic diseases are the results of deviated baseline B&C processes, the CNS plays a role in maintaining deviated baseline B&C processes, and protects the body state of a fully developed disease. The three CNS roles can explain that cancer progresses with increasing malignancy, cancer quickly returns after a surgery, cancer cells repopulate after chemotherapy and radiotherapy, cancer patients develop drug resistance inevitably, immune cells rebound after suppression, etc. We further showed that long-term exercises generally can correct part of the departures in B&C processes and thus help to reverse chronic diseases. Finally, we propose strategies for resetting the CNS’ state memory as an essential condition for curing chronic diseases and cancer.

Dose Response of Total Saponins Isolated from the Stem Bark of Dialium Guineense

The safety of plant-derived bioactive compounds has become a global concern. The present study investigated the dose response of total saponins isolated from the stem bark of Dialiumguineense. Adultmale Wistar rats (n = 15) weighing 170 – 190 g (mean weight = 180 ± 10 g) were randomly assigned to three groups (5 rats per group). The rats received varied doses of total saponins isolated from the stem bark of the medicinal plant (50 - 150 mg/kg body weight, bwt) orally for a period of 9 days. The concentration of fasting blood glucose (FBG) was used as the therapeutic index.The results of the analysis revealed that total saponins isolated from the stem bark of D. guineense significantly reduced the Fasting Blood Glucose (FBG) levels of normal Wistar rats (p < 0.05). The graded and quantal dose-response curves showed that150 mg/kg bwt was effective in reducing the blood glucose of rats (produced the best hypoglycemic effect). The study concluded that total saponins isolated from the stem bark of D. guineense possesses hypoglycemic effect at a relatively good dose.

Stem Cell Differentiation Stage Factors (SCDSFs) Taken from Zebrafish Embryo during Organogenesis and their Role as Epigenetics Regulators able to Reverse Neurosensory Hearing Loss

This translational paper discusses differentiation‑stage factors from zebrafish embryos as epigenetic regulators with potential to reverse neurosensory hearing loss. It outlines experimental evidence, delivery concepts, and research gaps.

Functional State Hardware Evaluation System in Educational Medium

Diagnosis of heart rate variability as an indicator of the impact of external and internal media can serve to make changes in the educational environment. The approach to the organization of the educational process is developed on the basis of quantitative indicators of the students’ functional state using the hardware-software complex " Varikard ".

Evolution of the Solid Human Tumor Cells Properties in Various Experimental Systems in Vitro

Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.

Proplastids and Juvenile Chloroplasts in the Apical Meristem of Flax

The apical meristem of plants comprises proplastids and juvenile chloroplasts. This work considered the most initial stages of the transition from proplastid to chloroplast. Ultrastructural analysis of apical meristem sections showed the formation of chloroplast envelope membranes and the synthesis of thylakoid membranes to be independent processes, and the production of thylakoid membrane proteins to directly involve cytoplasm ribosomes.

Evaluation of Inflammatory Serum Cytokines after Treatment with the Consciousness Energy Healing Based Proprietary Test Formulation on Combination of Cecal Slurry, LPS and E. Coli Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

Sepsis is a systemic inflammatory response to a confirmed or suspected infection. The transition from sepsis to septic shock causes high rate of mortality. The aim of this experiment was to evaluate the anti-inflammatory potential of the Biofield Energy Treated (Blessed) Proprietary Test Formulation and Biofield Energy Healing (Blessing) Treatment per se to Sprague Dawley rats on Cecal Slurry, LPS, and E. coli-induced systemic inflammatory response syndrome (SIRS) model. In this experiment, various proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, 1L-17, and interferon-γ (IFN-γ) were analysed using ELISA. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment remotely for about 3 minutes by a renowned Biofield Energy Healer Mr. Mahendra Kumar Trivedi. The level of TNF-α was significantly reduced by 40.50%, 85.36% (p≤0.01), 50.66% (p≤0.01), 87.38% (p≤0.01), and 58.63% (p≤0.01) in G5 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation), G6 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se to animals from day -15), G7 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treated test formulation from day -15), G8 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se + Biofield Energy Treated test formulation from day -15), and G9 (Cecal Slurry, LPS, and E. coli + Biofield Energy Treatment per se animals + untreated test formulation) groups, respectively as compared to the disease control (G2) group. Additionally, the level of IL-1β was decreased by 17.04%, 15.56%, and 12.59% in G6, G8, and G9 groups, respectively as compared to the untreated test formulation (G4) group. The level of IL-6 was significantly (p≤0.001) reduced by 36.18%, 50.24%, 43.25%, 52.69%, and 38.23% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. The level of IL-10 was altered by 70.53%, 49.25%, 60.18%, 41.54%, and 58.89% in G5, G6, G7, G8, and G9 groups, respectively as compared to the G2 group. Moreover, the level of IL-12 was decreased by 30.24%, 31.67%, 29.82%, 45.77%, and 50.54% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. The level of IL-17 was reduced by 48.75%, 59.61%, 59.28%, 62.49%, and 58.65% in the G5, G6, G7, G8, and G9 groups, respectively as compared to the G2. IFN-γ expression was reduced by 49.56%, 24.09%, 23.7%, 56.98%, and 44.94% in G5, G6, G7, G8, and G9 groups, respectively than G2. Overall, the data suggested anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications in preventive treatment groups viz. G6, G7, G8, and G9.

Antioxidant and Anti-Inflammatory Activities of Biofield Energy Treated Proprietary Test Formulation in Brain Tissues in Cecal Slurry, LPS and E. Coli-Induced Systemic Inflammatory Response Syndrome (SIRS) in Sprague Dawley Rats

Adjacent Segment Disease Associated with Klippel-Feil Syndrome: A New Classification System with Corresponding Therapeutic Options

Background Klippel-Feil Syndrome (KFS) is described as the clinical triad of short neck, low posterior hairline, and limitation of neck mobility. Objective Topresent our clinical experience with KFS patients who also had adjacent segment disease (ASD) and to propose a novel classification system for these patients. Methods This retrospective study was performed in the neurosurgery department of our tertiary care center. Data were gathered using the medical records of 22 KFS patients (10 males, 12 females) with ASD. Diagnosis was confirmed with imaging modalities including X-ray, computerized tomography, and magnetic resonance imaging. Clinical and radiological findings as well as therapeutic outcomes were noted. Results The average age of our series was 56.09 (range: 41 to 67) years. The operative technique was selected as for our novel “Yilmaz-Yucesoy Classification System”. Accordingly, one patient (4.54 %) received non-surgical treatment (Yilmaz-Yucesoy Grade 1), six cases (27.27 %) underwent anterior cervical arthroplasty, seven patients (31.81 %) underwent anterior cervical discectomy or corpectomy and fusion with cervical cage and plate (Yilmaz-Yucesoy Grade 3). Eight patients (36.36 %) with cervical spinal instability had anterior cervical discectomy or corpectomy and fusion with cervical cage and plate (Yilmaz-Yucesoy Grade 4). No mortality or remarkable complications were detected. Conclusion Appropriate and timely recognition and classification of patients with KFS and ASD based on our newly proposed “Yilmaz-Yucesoy Classification System” yielded promising treatment outcomes. However, further prospective, randomized, controlled trials are warranted on larger series to validate our preliminary results.  

Therapeutic Potential of Autologous Adipose Derived Mesenchymal Stem Cells in Human POI and Ovarian Aging

Background Women play an important role in the work setting. This leads them to put off their motherhood, sometimes preventing them from getting pregnant. Delaying pregnancy face women with low ovarian response, such as in Premature Ovarian Insufficiency (POI) or Ovarian Aging (OA). There is no current treatment, although there is evidence of improving ovarian function by inyecting mesenchymal stem cells (MSC). Materials and Methods Prospective, observational study of 17 women who attended Pronatal Clinic from 2019 to 2020. Each patient was registered in Assisted Reproductive Treatment (ART) and was enrolled in ovarian treatment with an autologous adipose tissue Mesenchymal Stem Cell (AD-MSCs) protocol. Three groups were assembled: 1) Control: AMH >1.2 ng/mL, without AD-MSCs, 2) POI/OA: female infertility due to POI/OA with AMH <1.2 ng/mL and 3) Amenorrhea: female infertility due to POI/OA with amenorrhea and AMH <1.2 ng/mL. Variables: Age, weight, height, serum AMH, endometrial thickness, follicular size and number on day 2 and 11 of the menstrual cycle, oocyte number, number of blastocysts and pregnancy rate. Results Between month 2 and 5, after AD-MSCs inyection, POI/OA group showed an increase in follicle number (2 to 9) and size (13.5 to 15.5 mm) on day 11 of the menstrual cycle, which resulted in a higher number of MII oocytes (2.6 to 4.2), and an increase in number of blastocysts (0 to 3) and endometrial thickness (8.6 to 9.4). Regarding the Amenorrhea group, a reboot in menstrual cycle was observed, although no further development of blastocyst was found. Conclusion The AD-MSCs inyection directly in the ovary allowed an increase in number of blastocysts and improved pregnancy rates in POI/OA patients.

Clinical Gastroenterological Manifestations as Criteria for the Pathology and Effectiveness of Surgical Correction of Reflux Disease of the Digestive System

The presence of numerous complaints of a gastroenterocolitic nature in patients with proven NBZ and CNDP and a sharp regression of these complaints after surgical correction of NBZ and CNDP allows us to conclude that the causes of these pathological manifestations are the failure of the Bauhinia valve and chronic violation of the duodenal patency, and the most adequate surgical aid for elimination of clinical manifestations of reflux disease is bauginoplasty with simultaneous duodenojejunostomy.

Cell Therapy as an Alternative approach for COVID-19 Infection Consequences: A Non-Systematic Review

The current uncontrollable outbreak of novel coronavirus (COVID-19) has unleashed severe global consequences in all aspects of life and society, bringing the whole world to a complete halt and has modeled significant threats to the global economy. The COVID-19 infection manifests with flu-like symptoms such as cough, cold, and fever resulting in acute respiratory distress syndrome (ARDS), lung dysfunction, and other systemic complications in critical patients are creating panic across the globe. However, the licensed vaccine has started to show up; some resulted in side effects that would limit its possibility in some circumstances as allergic personnel, for example. Moreover, the production and approval of new drugs is a very complicated process and takes a long time. On the other hand, stem cells have gone the extra mile and intensively investigated at preclinical and clinical studies in various degenerative diseases, including infectious ones. Stem cells are proposed as a broad-spectrum therapeutic agent, which may suppress the exaggerated immune response and promote endogenous repair by enhancing COVID-19 infected lung microenvironment. Also, stem cells have different application manners, either direct transplantation, exosome transplantation, or drug delivery of specific cytokines or nanoparticles with antiviral property by engineering stem cells. This review discusses and summarizes the possible emerging role of cell-based therapy, especially stem cell therapy, as an alternative promising therapeutic option for the treatment and control of novel COVID-19 and its potential role in tissue rejuvenation after COVID-19 infection.

Conclusion from the Doctor's Dissertation Martynov V.L. on Surgical Correction of Digestive System Refluxes

Annotation On the basis of 40 years of work on the treatment of 415 patients with gastroenterocolitis clinic, the author revealed the presence of refluxes due to anatomical defects of the Bauhinia valve (its failure) and the duodenum (chronic duodenal obstruction) at all levels of the gastrointestinal tract. After surgical correction of these anatomical breakdowns, the author states a significant improvement in all indicators of the state of both the digestive system and some extraintestinal manifestations, possibly the onset of precancer. The results obtained allowed the author to conclude that there are no "functional" disorders, this is only the level of our knowledge. Operations have been developed to correct the failure of the Bauhinia flap, intraoperative prevention of refluxes, and indications for methods of correcting chronic disorders of duodenal patency.

A Systematic Review of the Antimony Content of the Normal Human Prostate Gland

The prostate gland is subject to various disorders. The etiology and pathogenesis of these diseases remain not well understood. Moreover, despite technological advancements, the differential diagnosis of prostate disorders has become progressively more complex and controversial. It was suggested that the antimony (Sb) level in prostatic tissue plays an important role in prostatic carcinogenesis and its measurement may be useful as a cancer biomarker. These suggestions promoted more detailed studies of the Sb content in the prostatic tissue of healthy subjects. The present study evaluated by systematic analysis the published data for Sb content analyzed in prostatic tissue of “normal” glands. This evaluation reviewed 1998 studies, all of which were published in the years from 1921 to 2020 and were located by searching the databases PubMed, Scopus, ELSEVIER-EMBASE, Cochrane Library, and the Web of Science. The articles were analyzed and “Median of Means” and “Range of Means” were used to examine heterogeneity of the measured Sb content in prostates of apparently healthy men. The objective analysis was performed on data from the 23 studies, which included 1173 subjects. It was found that the range of means of prostatic Sb content reported in the literature for “normal” gland varies widely from 0.0066 mg/kg to 0.071 mg/kg with median of means 0.0085 mg/kg on a wet mass basis. Because of small sample size and high data heterogeneity, we recommend other primary studies be performed.

GATES/GEB as the Best Thermodynamic Approach to Electrolytic Redox Systems - a Review

The Generalized Approach To Electrolytic Systems (GATES) provides the best possible thermodynamic formulation of redox and non-redox, equilibrium and metastable, mono-, two- and three-phase systems, with all attainable/pre-selected physicochemical knowledge involved, without any simplifying assumptions made for calculation purposes, where different species may occur in batch or dynamic systems, of any degree of complexity. The Generalized Electron Balance (GEB) is the key concept completing the set of algebraic balances referred to redox systems, described according to GATES/GEB ⊂ GATES principles. The GEB, considered as the law of Nature, is fully compatible with charge and concentration balances, and relations for the corresponding equilibrium constants. Within GATES, the electrolytic systems are resolvable with use of MATLAB, or other iterative computer programs, if all necessary physicochemical knowledge is attainable.

Health Systems of Underdeveloped and Developing Countries

The right to health and access to health care are basic human rights, yet the relationship between poverty, marginalization and access to services is often misunderstood or overlooked in health policies and in development actions. To build equitable health systems a rights-based approach to reform and planning is needed. This involves a wide range of interventions, all of which should ensure that investments in the health system will bring benefits to all members of society, especially the poorest and most marginalized

Response of Some Sunflower (Helianthus annuusL) Hybrid Cultivars as Influenced by Argel (Solenostemmaargel, Del. Hayne) and Nitrogen Under Irrigation in Sudan

A field experiment was conducted during 2017/2018 to assess the effects of Argel (Solenostemmaargel, Del. Hayne) and Nitrogen fertilizer on the performance of two Sunflower Hybrid cultivars, with the objectives to exploit an easy, economic, and accessible organic fertilizer, the Argel in the phase of the continuous increasing prices of chemical fertilizers.. This experiment was laid out on spilt-split-plot experiment in Randomized Complete Block Design (RCBD) with four replications. Observations were taken on some agronomic traits (Plant height (m), Leaf area (LA), leaf Number (NL), Leaf Area Index (LAI) and Mean Seed Weight). The results revealed that the application of Argel and Nitrogen fertilizer have significantly increased the leaf Area (F= 7.22, P < 0.001), Plant Height (F=2.68, P < 0.2001), Leaf Number (F= 3.90, P < 0.0024), Leaf Area Index (F= 3.83, P < 0.0026) and Mean Seed Weight of both Serena and Opera cultivars respectively compared to the control. However, the different treatments of Argel and Nitrogen reflected variable degree of increase for the studied parameters. The study concludes that Argel is very promising, therefore a further study with different levels of Argel including other plant parameters is recommended.

Biomedical Infophysical Models of Filtering Ghost Airflows by Wearing Masks and Maintaining Social Distancing to Prevent COVID-19 and Reopen All Systems after Shutdowns (Lockdowns)

The COVID-19 pandemic has killed more than 400 thousand and infected more than 7 million people in the whole world as of 06/10/2020. Many open systems, such as educations, transportations, entertainments, sports or foods, have been completely or partially locked down in many regions of the world to prevent COVID-19 spreading. Therefore, how to reopen all of the open systems after the shutdown has become a world urgent issue. Evidences of COIVD-19 have showed: person-to-person transmission occurs among close contacts; virus droplets (or aerosols) play an important role in the transmission; people can prevent COVID-19 by measures of mask-wearing or maintaining social distancing. However, how these measures work to prevent COVID-19 is still not clear in a perspective of biomedical Infophysics. In this study, (1) we think the transmission of infection can be accomplished by real or virtual person; (2) we define a virtual person as ghost airflow, a term we coin to describe virus droplets (or aerosols) that are initially generated by human carriers and remain in the air to be transmitted. These ghost airflows are as dangerous as the real virus carriers particularly in enclosed (confined) environments; (3) we propose biomedical infophysical models (BMIPM) of filtering the ghost airflows by mask-wearing and maintaining social distancing, to help people to understand the filtering mechanisms and willingly follow the guidelines of preventing covid-19, and therefore to successfully reopen all of the open systems after the shutdowns (lockdowns) and (or) to avoid the shutdowns (lockdowns) in future epidemics or pandemics. Significantly, we compare the prevention efficiencies of COVID-19 between people who are accustomed and not accustomed to masks based on the published WHO, CDC or NHC pandemic data. The compared results support our models in this investigation. Coronaviruses easily survive and have high toxicity, in dirty, wet and cold environments, and the air pollution is linked with higher COVID-19 death rates. The dingy environments and air-conditioning, freezing systems sufficiently provide such necessary dirty, wet and cold conditions and polluted airflows to exacerbate the mortality rate of COVID-19. Therefore, we strongly suggest: to use air conditioners as less as possible, to turn the wind levels as low as possible and to clean (disinfecting) the air-conditioning systems (filters and channels) and environments as frequent as possible.

Proposed Spray System for Family Agriculture with A Remote-Controlled UAV (Small Drone or Helicopter) and An Economical Sprinkler

In the country, food production is more compromised every day, despite zero efforts and government, agricultural and livestock sector, causing poverty, migration, marginalization among other social disorders in addition to food insecurity. In Mexico 34% of the population is engaged in agricultural tasks, with very small land areas. The fact that 85% of do not have more than 5 ha of arable land, and that among them, 90% do not reach 3 ha clearly indicates their great need for light machinery .The solution to these problems family farmers are provided with affordable technologies to increase their productivity. One of the most common problems in agriculture is the application of agrochemicals, which is tedious and dangerous when farmers are exposed to these highly toxic products, therefore a system is proposed is through the help of a drone or remote control helicopter, both of economic type connected by a hose to the sprinkler and a tank. Due to the danger of applying agrochemicals for family farmers who rarely follow the precautions to apply these products, the proposed alternative is attractive for small agricultural properties, although it is not free of cost, the drone and the optimal sprayer should be investigated.  

Formulation of Isohydricity Conditions in Acid-Base systems - A Review

The isohydricity conditions are formulated for D+T systems composed of titrand D and titrant T, mixed according to titrimetric mode; only acid-base equilibria are involved there. The original method of dissociation constants determination, based on the isohydricity principle, is presented and confirmed experimentally. The pH titrations in the system of isohydric solutions are also put in context with conductometric titrations.

Influence of Carbon - Nitrogen Supplements and pH on Growth of Sugarcane Stem rot Pathogen Fusarium Solani NVS671

Fusarium solani NVS671 identified from infected sugarcane stem of Co 671 as a new pathogen was subjected to various cultural conditions to understand its physiological profile. In continuation with our previous work, cultural analysis was carried out under in vitro condition by supplementing various carbon and nitrogen sources in Czapek-Dox agar (CDA). Under different hydrogen ion concentrations, it was found that the growth of Fusarium solaniNVS671 was less at pH 4 and pH 10 and could reach up to 5 cm after 7 days of incubation on Potato Dextrose Agar (PDA). It is observed that the pH around 7 to 8 was optimum for the growth of F. solani. Ten different nitrogenous (N) sources and nine different carbon sources were tested on CDA medium to know their effect on the mycelial growth rate and characteristics of the fungus. Among the N sources evaluated, ammonium chloride (7.96±0.11 cm) was found to be most efficient for mycelial growth promotion followed by ammonium nitrate (7.7±0.1 cm) and ammonium sulphate (7.3±0.1 cm). The most preferred carbon source recorded to promote best radial mycelial growth was starch (7.96±0.05 cm) and sucrose (7.93±0.05 cm). Capabilities of using different carbon and nitrogen sources and ability to grow at different pH levels may allow species to adapt to specific soil conditions.This study is important to understand the physiology and metabolite preference of F. solani.

Analysis and Forecast Based on the Kinetic Equation for Changing the Numerical Composition of Living Systems

The possibility of applying the kinetic theory of aging of biological species published earlier by the authors of this work to assess and predict changes in the number of specific populations is evaluated. The populations of the USA, China and Russia, as well as the population of mice observed in the experiment "mouse paradise" of the American scientist John Calhoun are considered. To this end, a historically consistent analysis of the main previously proposed multi-scenario mathematical models describing demographic data and predicting the dynamics of the population was performed. The results of these models show a decrease in the population growth rate, a tendency toward a limit with an increase in historical time, the achievement of such a limit in some developed countries with a relatively high level of social security, a subsequent decrease in the number and further uncertainty of the final population outlook in the distant future. In addition, these models made it possible to establish that the observed population growth in developed countries is unambiguously accompanied by its aging - a relative predominant increase in the number of elderly people compared to the number of the younger generation (people are aging, the population of countries is aging). In this work, the assumption was made and confirmed that the dynamics of the aging of the population of the countries of the World corresponds to the dynamics of aging of a person of one generation and is mathematically described by the differential equation of the kinetic theory of aging of living systems of the same type with close values of the parameters. The biophysical meaning of the parameters of the kinetic equation reflects G. Selye's concept of the determining role of stress in human life and populations. An analysis of the changes in the numbers of the considered populations of humans and mice at various stages of their development is qualitatively commented on from the standpoint of comparative tension according to G. Selye. To assess the degree of aging of a biological object of one population in kinetic theory, the probability of death during life is selected as an indicator of aging. In this work, the probability of reaching the maximum population size was chosen as an indicator of the aging of a biological object of various populations. The published literature predicts various options for changing the population after reaching a maximum - maintaining the reached maximum level and decreasing to a certain limit, less than the maximum achieved. In this paper, based on an analysis of its results and an analogy with the complete degeneration of mice in the “mouse paradise” experiment, a conclusion is drawn about a hypothetically possible third variant of the limiting decrease in the population - its complete degeneration.

Sustained Clinical Response of Pseudotumoral Lesion of the Central Nervous System in Behcet's Disease After Treatment with Infliximab. Case Report.

This case documents a pseudotumoral CNS lesion in Behcet's disease with sustained response to infliximab therapy. Clinical evolution, neuroimaging changes, and rationale for TNF‑alpha inhibition are detailed. The report supports considering biologic therapy for refractory neuro‑Behcet manifestations under specialist guidance.

Triacontanol Alleviated Nickel Toxicity in Maize Seedling by Controlling Its Uptake and Enhancing Antioxidant System

Triacontanol (TRIA) role in improving growth, physiological activities and tolerance against abiotic stresses has been reported. Yet, the mechanism by which TRIA executes its effects remains elusive. This work therefore studied the possible role of TRIA exogenous application in counteracting the adverse effects of nickel (Ni) treated maize seedlings. Maize seedlings (15-day-old) were grown in washed sand irrigated with nutrient solution provided with 100 μM NiCl2. Two concentrations of TRIA (25 and 50 µM) were applied twice as a foliar spray for Ni-stressed seedlings. Shoot and root growth attributes, Ni content, and antioxidant defence systems of maize seedlings were determined. Ni treatment reduced the shoot and root length and biomass, causing necrosis of the old leaves,greater reduction was shown in the roots. The shoot and root length was negatively correlated with their Ni content, which was consistent with their content of H2O2, but not with their malondialdehyde (MDA) content. As the roots had the greatest Ni content, maximum peroxidase (PX) and glutathione reductase (GR) activity as well as the highest ascorbic acid (ASA) and reduced glutathione (GSH) content were observed in the roots. The Ni-induced deleterious effects were alleviated by foliar application of TRIA concentrations. Also, TRIA treatment minimized root Ni content, whereas it maintained the shoots unharmed by Ni. Such mitigative effects of TRIA are explained by its key role in enhancing antioxidant capacity (expressed as IC50), increased PX and ascorbate oxidase (AO) activity, GSH, and total phenolic contents.

Mathematical Analysis of Alternative Power Systems in a Northern Wisconsin Home

The effects of global warming have been causing irreversible damage to the Earth over the past decades. One way we can reduce our individual impact on the environment is to focus on the production and consumption of Eco‐friendly sources of electricity such as solar, wind, or bio-electric energy. Based on the current available and suitable energy options, we have proposed to modify a chosen house from Northern Wisconsin by using a hybrid system including solar energy and wind turbine energy to replace the traditional power grid. Considering sunlight‐time, wind speed in Northern Wisconsin, we have predicted the immediate and long‐term fiscal and environmental impacts. From this cost‐benefit analysis, we project that the best hybrid option is a combination of 95% solar power and 5% wind energy, which would save about $41,000 over the next 30 years.

Effects of Involuntary Smoking and Vaping on the Cardiovascular System

In deaths and diseases attributed to tobacco smoke cardiovascular events exceed cancer and respiratory diseases. Second hand smoke promotes the development of arteriosclerosis and can trigger acute changes of endothelial function and blood coagulability. Indoor smoking bans reduced coronary syndrome and myocardial infarction 10-20% within one year and were followed by sustainable decreases of stroke and diabetes. With a smoke-free hospitality industry people recognized tobacco smoke as an air pollutant, smoking in public was denormalized and social acceptance of smoking in front of children and pregnant women decreased also in homes and cars. Combined effects with ambient air pollution are proven for active smoking and suspected for SHS. Contamination with third hand smoke (THS) persists for months in homes and cars, creating secondary pollutants that in some cases are more toxic (e.g. nitrosamines). Remnants found in air, dust, and on surfaces (carpets, wallpapers, upholstery, soft toys) were associated with their metabolites in saliva of children and in urine of nonsmokers residing in homes previously occupied by smokers. In animal experiments effects of THS were found on thrombogenesis, insulin resistance through oxidative stress, on the developing immune system, lipid metabolism and alterations in liver, lung, skin and behavior. Much less is known about health effects for bystanders from the aerosols exhaled during “vaping” of e-cigarettes, but nicotine and other toxins from e-cigarettes are certainly a hazard, which should be prevented by the use of dermal and oral nicotine products, which are safer for nicotine replacement and without risk for bystanders.

Geomatic Tools for Water Management in a Community Irrigation System, Cruz del Eje, Córdoba.

An integral and efficient management of water for irrigation requires the adoption of new technologies to respond to the challenges imposed by the agricultural sector, in particular to stabilize production through the adequate use of water resources. In this sense, it is vital to characterize and know the amount of area which is under irrigation in such agricultural systems. In this paper we show the use of satellite information data in a GIS environment with the objective of characterizing the productive areas under irrigation in Cruz del Eje, Córdoba, Argentina in 3 types: A) irrigation region B) irrigable area and C) actually irrigated area. Multitemporal image indices and segmentation were used for this characterization and then maps of these 3 types of agricultural land cover were generated. Additionally, we present simple satellite images processing and classification procedures to increase the knowledge about the land cover over this irrigated area. Finally, we discuss how this geographically explicit information generated could be useful for the decision-making process on current irrigated areas and on the potential of productive systems through community irrigation systems.

Trigonella Foenum Graecum Extract Benefits on Hematological, Biochemical and Male Reproductive System as a Complementary Therapy with Glimepiride in Treating Streptozotocin Induced Diabetic Rats

Diabetes mellitus (DM) is a chronic metabolic disorder. Streptozotocin is a naturally occurring cytotoxic chemical, particularly toxic to the pancreas and insulin producing beta cells in mammals and induces diabetes. Glimepiride is a second generation sulfonylurea, used as second-line or add-on treatment options for type 2 diabetes. Fenugreek (Trigonella foenum graecum) seeds have been documented as a traditional plant treatment for diabetes. Soluble dietary fiber of Fenugreek significantly improved oral glucose tolerance in diabetic rats. It also exerts anti-diabetic effects mediated through the inhibition of carbohydrate digestion and absorption and the enhancement of peripheral insulin action.  Most herbal remedies can interact with allopathic drugs resulting in altered activity and toxicity. At the same time, herbal remedies might produce the same kind of effects as the drug produce. Current published research information on herb-drug interactions is scanty. So, the aim of this study was to investigate the possible interaction between conventional drug used for the management of diabetes; (Glimepiride) and a traditional herbal remedy; Fenugreek aqueous extract in Streptozotocin induced diabetic male albino rats. In conclusion, combination therapy induces better hematological, biochemical effects and improves the oxidative stress biomarkers and antioxidant enzymes. Histological studies showed better results on some organ functions. The results emphasize the benefit of using the combination of Fenugreek seeds aqueous extracts as supportive complementary anti-diabetic therapy.

Women’s Empowerment and the Integration of Traditional Maternal and Child Healthcare with National Health Systems in the Republic of Guinea.

Several studies show that policies to improve maternal and infant health must be contextualised within broader questions and commitments concerning women’s empowerment. There are, however, two-way linkages between women’s empowerment and reproductive services. Certain institutional approaches that support women’s reproductive health can themselves be experienced as empowering whereas others, however well-meaning, can be experienced as disempowering, undermining health and broader goals. It is thus important to discern and support those elements of reproductive services that might have empowerment outcomes, and to avoid others that undermine them. This paper is premised on the hypothesis that approaches to reproductive health that are rooted in women’s life worlds, that support women’s social networks and which enhance women’s confidence and control will have very different empowerment effect from those that subordinate women and their networks to external expertise and (often male) authority and undermine women’s preferences or autonomy. We (a) conduct an audit of positive practices concerning maternal and child health and (b) examine how current support to maternal and infant health articulates with this. Analysis seeks to reposition indigenous knowledge, community wisdom and their secular practices in a way that promotes better health provision that is integrated with these existing practices and that is empowering.

Efficacy of DHA and EPA on Serum Triglyceride Levels of Healthy Participants: Systematic Review

Background Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are categorized as omega-3 poly unsaturated fatty acids (PUFAs) that are present in fish oil, etc. DHA and EPA omega-3 PUFAs have a well-established fasting serum triglycerides (TG) lowering effect that may result in normal lipidemia in hyperlipidemic patients. In general, omega-3 PUFAs, such as DHA and EPA, can be ingested easily, and because they are highly safe, they are assumed to be suitable for controlling fasting serum TG in the serum of those who do not require drug treatment. To the best of our knowledge, however, almost all systematic reviews on the effects of omega-3 PUFAs on lowering fasting serum TG are directed at patients fulfilling the diagnostic criteria of dyslipidemia. Objectives To review and confirm the preventive effect of omega-3 PUFAs against hypertriglyceridemia or the effect on nondrug treatment in patients with a mild disease, a systematic review was conducted to determine whether there was a fasting serum TG-lowering effect in subjects without disease and those with a slightly higher triglyceride level who consumed DHA and/or EPA orally compared to those with placebo or no intake of DHA and/or EPA. Search Methods We evaluated articles from searches of PubMed (1946-February 2016), Ichushi-Web (1977-February 2016), and J Dream III (JST Plus, 1981-February 2016; JMED Plus, 1981-February 2016). The keywords were set as follows: “DHA” or “docosahexaenoic acid” or “EPA” or “eicosapentaenoic acid” and “TG” or “triglyceride” or “triglycerol” or “triacylglycerol” or “neutral lipid.”. In addition to the literature group obtained by the database search, we included participants not suffering from any disease (i.e., excluding mild hypertriglyceridemia). Eligibility Criteria Before the test selection process, the following inclusion criteria were defined. Participants were healthy men and women including those with mild hypertriglyceridemia (fasting serum TG level, 150-199 mg/dL [1.69-2.25 mmol/L)). Intervention was defined as orally ingested DHA and/or EPA. Comparison was made to placebo intake or no intake of DHA and/or EPA. Results were measured for the fasting serum TG level. The test design was RCT, and quasi-RCT. Data Abstraction Various characteristics were extracted from original reports using a standardized data extraction form, including the author of the study, research year, research design, subject characteristics (sex, age, sample size), period, dose of DHA and/or EPA (mg/day), and comparison group. Main Results We identified 37 documents for review. Among the 37 reports used to integrate literature results, 25 revealed a decrease in fasting serum TG level ​​due to the oral ingestion of DHA and/or EPA. Sixteen studies on subjects without disease and 21 on subjects with slightly higher fasting serum TG levels were separated and stratified analysis was conducted. Ten of the 16 (normal TG participant) and 15 of the 21 studies (slightly higher TG participant) respectively, indicated that at least 133 mg/day of DHA and/or EPA intervention provided a statistically significant decrease in the fasting serum TG level between an intervention group versus a placebo group.

Investigation of Antimicrobial Activity of the Extracts of the Leaves, Stembark and Root of Allanblackia floribunda: An Alternative Paradigm Shift Outcome.

Over the years, plants have been a major source of medicines, especially in the rural areas of the developing communities, with probably lack of functional health care facilities and trained health care personnel on hand for emergency medical response. However, with the dynamics and improvement in science and medicine, chemically synthesized drugs were being introduced and used to treat myriad of critical illnesses across board. Nonetheless, these were further strengthened owing to the increasing trend of drug resistance outcome, especially by the emerging and re-emerging infectious microorganisms. Thus, in the light of the above, there is a gradual but increasing steady return to the use of plants as sources of medicine and treatment of antibiotic resistance pathogens and illness across the globe. This study therefore, explores the use of antimicrobial activity of the leaves, stembark and root of Allanblackia floribunda on four bacterial isolates namely Staphylococcus aureus, Escherichia coli, Pseudomonas sp. and Bacillus sp. Methylated spirit, ethanol and distilled water were used as the extraction solvents differently. Ethanol extracts proved to be a better solvent compared with the other two while the extracts from distilled water were not active against any of the isolates. However, all the three ethanol extracts were more active against S. aureus while Pseudomonas sp. showed a higher level of resistance to the extracts. The leaves and root of the plant were more active on most of the isolates compared with the stembark as shown in the results section.  

Enhanced Alkaloid Production from Cell Culture System of Catharanthus roseus in Combined Effect of Nutrient Salts, Sucrose and Plant Growth Regulators

Callus and biomass culture of Catharanthus roseus L. were established to check for the presence of total alkaloid and its subsequent yield. Various treatments like strength of nutrient salts, sucrose concentrations and combinations of plant growth regulators (PGR’s) were applied to both MS and B5 in agar as well as suspension medium to test their effects on enhanced alkaloid content and its yield. There was no significant difference in any of the observable parameters of fresh wt, dry wt, alkaloid content, production, productivity and yield if the culture were treated similarly in both types of media formulations (MS or B5 salts). Physical state (agar solidified or the liquid suspension) of the medium had significant effect on all the parameters particular on fresh wt, alkaloid content and yields. Although, the fresh wt. and dry wt. of biomass in suspension culture was 2-3 times less than that of callus obtained from agar medium. However, the alkaloid content and yield was 2-3 times higher in suspension culture compared to agar medium in similar treatments. The highest alkaloid content observed was 5.67mg/g dwt in B5 suspension medium containing 3% sucrose and modified with 0.5mg/l 2,4-Dichlorophenoxy acetic acid (2,4-D) + 1 mg/l Kinetin (KIN) + 2mg/l α- naphthalene acetic acid (NAA). The combined effects of these factors on the enhanced production of total alkaloids were expected to contain higher yield of anticancer vinblastine and vincristine in the cell suspension culture system.

Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

Acute and Subacute Toxicity Evaluation of the Stem Bark Aqueous Extract of Harungana Madagascariensis in Rodents

The present investigation was carried out to evaluate the safety of a stem bark aqueous extract of Harunganamadagascariensis Lam. (Hypericaceae) by determining its potential toxicity after acute and subacute administration in rodents. Acute toxicity tests were carried out in mice and the behavior, death and median lethal dose (LD50) were estimated. Subacute toxicity (28 days) studies were conducted in rats with oral daily doses of 200, 400 and 600 mg/kg. Parameters observed at the end of the subacute tests included changes in body and vital organ weights, mortality, hematological, biochemical, hepatic and kidney effects. Harunganamadagascariensisextract did not produce any visible toxicity or mortality with oral doses up to 2000 mg/kg within 14 days of single treatment, leading to the conclusion that the LD50 is greater than 2000 mg/kg. In the subacute toxicity tests, neither mortality nor visible signs of lethality was seen in rats. No significant change in the weight of the kidney, liver, heart, lungs spleen, pancreas and testicles was observed. Alanine transaminase (ALT) increased significantly in males at 400 and 600 mg/kg, whereas Aspartate transaminase (AST) decreased at 600 mg/kg in female rats. HDL Cholesterol was reduced at 600 mg/kg in female rats. There was a significant increase in urea concentration in female rats at 400 mg/kg. A significant decrease, both in platelet volume distribution (PVD) at 400 mg/kg in male rats and in red cell volume distribution (RDW) at 200 mg/kg were recorded in female rats respectively, but with no changes in other hematologic parameters. Histological study shows normal structure of liver, kidneys and heart of control and treated rats. Results indicate that oral doses of aqueous stem bark of Harunganamadagascariensis are relatively safe in rats; however, assessment of hepatobiliary function should be done during chronic use in humans.

The Balance 2∙f (O) – f (H) as a Cornerstone in Formulation of Electrolytic Systems

The Generalized Electron Balance (GEB) concept, related to electrolytic redox systems, is considered according to principles of Generalized Approach to Electrolytic Systems (GATES). Two equivalent Approaches (I and II) to GEB are presented. The Approach I, when perceived in convention of the card game, is based on the common pool of electrons as money, introduced by electron-active elements, named as players; electron-non-active elements are called there as fans. The GEB obtained according to Approach II results from the linear combination f12 = 2∙f(O) – f(H) of elemental balances: f1 = f(H) for H, and f2 = f(O) for O. Very important properties of f12 are presented here in details, and illustrated by a redox system where comproportion- ation reactions occur

Assessment of Energy of Consciousness Healing on Cell Growth of Plant Stem Cells Callus Culture

The present study was aimed to evaluate the effect of Consciousness Energy Healing Treatment on plant callus of Mandukparni (Centellaasiatica), Katsarika (Barleriacristata), and Amla (Phyllanthus emblica) in Murashige & Skoog liquid medium (MS) for its growth and yield on day 7. The plant callus of all the three plants were divided into two parts, one part received Biofield Energy Treatment remotely (known as The Trivedi Effect®-Energy of Consciousness Healing Treatment) by a renowned Biofield Energy Healer, Gopal Nayak and denoted as Biofield Energy Treated group, while another part did not receive any treatment and defined as control. Plants callus were observed on day 7 after treatment and visualized under phase contrast microscope for cell growth, captured photomicrographs along with wet weight compared with day 0. Results suggested that three plants viz. Mandukparni, Katsarika, and Amla callus after 7 days showed a significant improved growth rate as compared with the respective untreated groups. The weight of the callus growth (in mg) after Biofield Energy Treatment among Mandukparni, Katsarika, and Amla callus on day 7 was 630, 782, and 920 mg, respectively. However, the percentage increase in weight of the callus in Mandukparni, Katsarika and Amla was 11.1%, 52.4%, and 68.5%, respectively than untreated. Hence, results concluded a significant growth in callus weight after Biofield Energy Treatment, which suggested the action as complementary and alternate approach in order to produce most high-value phytoconstituents from plant callus that can be used for making various drugs, food flavoring and colouring agents.

Cancer Stem Cells: A Cause or A Consequence of Field Cancerization

A review discusses the relationship between cancer stem cells and field cancerization, considering bidirectional influences and implications for prevention and targeted therapy.

Morpho-Anatomical and Physicochemical Standardization of Diospyros malabarica (Desr.) Kostel Stem Bark

Diospyros malabarica (Desr.) Kostel synonym Diospyros peregrina Gurke (Family: Ebenaceae) is a medium sized evergreen tree commonly known as Kendu in Assamese. The plant has ethnomedicinal significance and used by various ethnic communities of North-East India to treat various disorders like dysentery, diabetes, diarrhea malaria, ulcer and wounds. However, detailed scientific information is not available to identify the plant material, in order to ascertain its quality and purity. Therefore, the present work was carried out to perform morpho-anatomical and physicochemical analysis of D. malabarica stem bark. The bark is externally dark brown to black in color and rough having characteristics odor and astringent taste. The microscopy of bark reveals the presence of polygonal thick walled cork, 3-4 layered phellogen, 7-8 layered phelloderm, stone cells, phloem fibers and medullary rays. Stem bark powder showed thick walled cork cells, thick walled elongated phloem fibers, lignified stone cells and rhomboidal crystals of calcium oxalate. Further, physicochemical analysis of the bark power showed loss on drying, total ash, water soluble ash, and acid insoluble ash as 6.2, 5.6, 1.1, 2.45, and 5.7% w/w respectively. The alcohol and water soluble extractives values of the stem bark were 10.6 and 16.8% w/w respectively. The result of preliminary phytochemical screening indicates presence of triterpenoids, saponins, tannins, flavonoids and sterols. The findings of this study will facilitate pharmacognostic standardization of the plant material and aid in the preparation of an herbal monograph for the species.

Formation of Proplastids in the Apical Meristem of Wheat

The apical meristem of the growing point of plants contains proplastids, precursors of chloroplasts. The main attention of investigators was paid to the transformation of proplastids into chloroplasts. The formation of proplastids of the apical meristem of wheat seedlings was investigated in the present work and described for the first time in the scientific literature. Ultrastructural images of apical meristem areas showed that the formation of the proplastide body includes several stages: localization of plastid DNA in the cytoplasmic matrix in close contact with cytoplasmic ribosomes, the formation of membrane vesicles containing plastid DNA, the step-by-step filling of these vesicles with dense contents, and the formation of mature proplastids. 

Knowing, Proposing and Acting: Epistemological Aspects of Medical Practice in the New Millennium.

In this work, it is analysed how the medical practice is imbued with Cartesian rational thought as well as empiricist thought and it is stated that medicine is an art and is science. It is proposed that the object of knowledge of the medical practice is not the concept of disease but health. It is from the concept of health and normality that medical taxonomy labels individuals as sick. This taxonomy is frequently re-evaluated and reorganized by scientific societies. This sometimes occurs according to new knowledge, but this categorization may also be questioned due to direct intervention or indirect pressure related to interests, especially economic, that are sometimes not clearly visible. Accordingly, an ongoing discussion is needed to keep the medical practice neutral against struggles of interest derived from the health industry. These topics must be considered and debated in medical schools including undergraduate and postgraduate programs.

Narcolepsy With or Without Cataplexy In The Pediatric Population: A Systematic Review

Study Objectives: Narcolepsy diagnosis has been associated with a long lag time between the onset of the disorder and the diagnosis itself among patients with the disorder. This article reviews the childhood epidemiology of idiopathic narcolepsy, including its prevalence, subtypes, and disease progression. Methods: A literature review was conducted to include both published and unpublished data on pediatric narcolepsy. All English language articles were included through April, 2015. Results: Time from symptom onset to diagnosis for children is approximately three years. The prevalence of cataplexy appears to be lower in children compared to adults, suggesting a later onset of cataplexy. The presence of cataplexy, however, was unrelated to demographic factors and laboratory findings. Conclusion: There is a substantial lag-time between initial symptom presentation and diagnosis in children with narcolepsy. A less quintessential presentation of narcolepsy might occur in children relative to adults, making diagnosis more challenging. Continued improvements in narcolepsy education for both pediatricians and parents might facilitate earlier identification and diagnosis of the disease, thus leading to improved outcome.

The Efficacy of Behavior Management for Depression in Dementia Patients: A Systematic Review and Meta-Analysis

Overview: Dementia is a serious brain disease that impacts negatively in several areas of patient’s functioning. Depression has a strong link with dementia and is part of the behavior and psychological symptoms (BPSD). Behavior management for depression is recommended as a first-line psychological treatment for dementia patients. However, there are no systematic reviews examining the efficacy of behavior management for depression in dementia. Objective: To examine the efficacy of behavior management (BM) for depression in dementia patients. Methods: Five electronic databases were searched (1999 to 2015) for randomized controlled trials (RCTs) which were selected according to eligibility criteria. Data was pooled, quality assessment was completed, and a meta-analysis was performed. Results: This review included ten randomized controlled trials. In the four studies where behavior management was a focused intervention, no significant treatment effect was observed (standardized mean difference SMD -0.20; 95 % CI -0.96 to 0.56). In the remaining six studies in which behavior treatment was involved as a component, the analysis showed a trend favored the intervention, but it was not significant (SMD -0.12; 95 % CI -0.25 to 0.01). Conclusion: There is no evidence for behavior management alleviating depression in dementia patients. Future research examining the efficacy of specific behavior management techniques for milder forms of dementia and multimodal interventions are recommended.

Successful Allogeneic Hematopoietic Stem Cell Transplantation from A 5/10 Mismatched Unrelated Donor in A Patient with Donor-Specific Anti-HLA Antibodies.

Hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor, an haploidentical donor or a cord blood unit (CBU) has become a widely aviable approach if patient lacks a matched related or unrelated donor. However, if the patient has anti-HLA antibodies against antigens present in the mismatched donor or CBU (donor-specific antibodies, DSAs) this option should be disregarded due to the high risk of graft failure. Desensitization can be used to reduce levels of DSAs but this technique has limited results. We report the case of a 62-year-old woman with DSAs against two haploidentical familiar donors who failed desensitization of DSAs. Finally she underwent a HSCT from a 5/10 mismatched unrelated donor which has been successful.

Implementing a Cold-Chain System for Nutritional Assessment in Rural Uganda; Field Experiences from FtF Nutrition Innovation Lab Cohort Study

Objective: To elaborate on the procedures undertaken to establish blood draws and cold chain for nutrition assessments. Setting: A total of 5,044 birth cohort households were enrolled and assessed using household questionnaires, anthropometry, and blood sampling to assess nutritional issues and exposures to environmental contaminants. The challenge was to obtain, transport, process, store, and analyze tens of thousands of serum samples obtained in sites that were often difficult to reach. Approach:  Before enrollment began, 24 healthcare facilities in the North and Southwest of Uganda were assessed for suitability as local nodes for processing and storage. Equipment needs included functional centrifuges, refrigeration, ice machines, and -20oC freezers. Other important physical infrastructure included the presence of backup power (generator or solar generated) in the event of electricity failure. Once samples were obtained, they were transported within 5 hours to the facility laboratories, where serum was separated and aliquoted into properly labelled storage tubes and then frozen. Relevant Changes: At community level, our team visited households or small group of household members close to their homes to reduce on travel time hence contributed to high retention rates. Our immediate testing for anemia and malaria results benefited enrollees and enhanced community acceptance. By using Village Health Teams (VHTs), we could accommodate household preferences for the timing of sample collection. Our engagement with phlebotomists transformed their role from a simple service into active team members. Lessons Learned: Our first lesson was that in our setting, the success of this nutrition biological sampling system required community engagement and acceptance. By combining an immediately actionable set of tests (for anemia and malaria), and visiting cohort households, we greatly enhanced the success of the system.

First Evidences of Epithelial-Mesenchymal Transition and Cancer Stem-Cell Phenotype Acquisition in Dermo-Epidermal Junction of BPV-Infected Neoplasms

Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).

A Pilot Trial of Applying Geographic Information System Technology to Health System Strengthening in the Upper East Region of Ghana

Despite widespread use of Geographic Information System (GIS) technology to strengthening health systems, the application of GIS to health systems strengthening in resource-poor Sub-Saharan Africa remains rare. Over the June 2012 to December 2013 period, the Ghana Health Service (GHS) conducted a pilot application of GIS to health systems development in one rural impoverished district of the Upper East Region (UER). Workers were deployed to gather coordinates of health care facilities throughout the UER. Coordinates were linked to routine health information data, and utilized to generate maps for guiding task prioritization. For example, geocoded Community-based Management of Severe Acute Malnutrition (CMAM) program data were used to target services in communities where the prevalence of childhood acute malnutrition was relatively high. GIS was pivotal in tracking and responding to infectious disease morbidity from causes such as diarrheal diseases and tuberculosis. UER Regional Health Administration (RHA) authorities are currently utilizing GIS to map antenatal care coverage, skilled birth deliveries, neonatal mortality, still births, family planning service caseloads as well as for targeting programmatic action. Experience emerging from this trial attests to the value of GIS in contributing to efforts to strengthen health systems in rural impoverished regions of Africa.

A Cost Analysis of Systematic Vitamin D Supplementation in the Elderly Versus Supplementation Based on Assessed Requirements

Hypovitaminosis D is common among older people and treatment with vitamin D is associated with reduced risk of falls and fractures. This paper provides a cost analysis of assessing the vitamin D status of and providing the pharmaceuticals for elderly citizens in Kalmar County, Sweden (population approximately 230,000). Four hypothetical interventions were analyzed: (a) systematic vitamin D/calcium supplementation to all elderly (≥75 years), (b) assessment of vitamin D status in elderly and supplementation to those with insufficient levels, (c) systematic vitamin D/calcium supplementation to all nursing-home residents, and (d) assessment of vitamin D status in nursing-home residents and supplementation to those with insufficient levels. The calculations were based on an estimated reduction in overall costs due to the assessed number of hip fractures after vitamin D/calcium supplementation. The annual net economic benefit of vitamin D/calcium supplementation was estimated at (a) €304,000, (b) €860,000, (c) €755,000, and (d) €740,000. The provision of systematic vitamin D supplementation to nursing-home residents would provide a substantial net economic benefit to society and assessment of the vitamin D status before starting supplementation does not seem to be necessary. Although assessment of all elderly citizens would be more comprehensive, the true proportion with insufficient vitamin D levels in the general population is uncertain and to reaching consensus on the most advantageous daily vitamin D intake, vitamin D blood levels are necessary. Also, systematic supplementation to all elderly would result in other outcomes that could be worth the cost, but that remains to be evaluated.

Development of a Chronic Obstructive Pulmonary Disease Severity Classification System Using A Japanese Health Insurance Claims Database

Background: Healthcare services provided to patients should vary depending on disease severity. However, disease severity bias, a type of selection bias, is a commonly encountered problem in administrative database studies. Herein, we selected chronic obstructive pulmonary disease (COPD), which commonly affects elderly Japanese citizens, for the development and validation of a severity classification system based on a health insurance claims database. Methods: Patients who received COPD-related diagnostic codes in 2011 were selected from a commercially based health insurance claims database. COPD patients were randomly divided into two groups to develop and validate severity scores. A principal component analysis was used to estimate factor loadings used to weight calculations of COPD severity scores. Score validity was evaluated using a linear trend test to predict COPD treatment costs and acute exacerbation events. Results: Using records from 880 patients, ten variables were created: acute exacerbation events, emphysema diagnoses, laboratory test and oxygen therapy procedures, prescribed anticholinergic, inhaled corticosteroid (ICS), short acting beta-agonist, and long acting bronchodilator (LABA) agents, asthma diagnosis and patient birth years. Factor loadings from LABA and ICS prescriptions had the strongest impacts on estimated severity scores (0.50 and 0.49, respectively). Among 300 validation group patients, scores were found to associate with increasing trends of median costs and exacerbation risks (p for trend < 0.05). Conclusions: Estimatedseverity scores would help to predict COPD-related medical costs and exacerbation events. For further clinical implementation, this classification system should be re-evaluated using clinical lung functions information indicative COPD severity and treatment choices.

Autism Spectrum Disorders and Gluten/Casein Free Diet Treatment: A Systematic Review (1990-2016)

Background: High number of patients suffering from autism spectrum disorders utilize dietary intervention methods, especially gluten-free/casein-free diet. In contrast with its’ extensive usage no sufficient and consistent data exist to support its’ efficiency and safety. Objective: The main aim of this systematic review is to provide a general look to the efficiency and safety of gluten-free/casein-free diet treatment for autism spectrum disorders. Method: Studies used in this systematic review are gathered from 3 online databases (PubMed, Embase and the Cochrane Library). Inclusion criteria are established for study selection. Articles published in a peer-reviewed article between 1990 and 2016 in English about our topic of interest and conducted with patients under the age of eighteen (18) are selected and further analyzed (“Level of Evidence” and “Grade of Recommendation” criteria are utilized). Results: Even though some studies with high values of “Level of Evidence” claim that gluten-free/casein-free diet is beneficial for patients suffering from autism spectrum disorders, studies with lower risk of bias demonstrate otherwise. Since studies such as case reports and cohort studies may contain bias associated with small sample size, absence of clear assessment methods, lack of randomization and short treatment period we suggest that there is no sufficient data to support gluten-free/casein-free diet treatment. Conclusion: Due to controversial outcomes from studies that have different “Level of Evidence” we speculate that efficiency of gluten-free/casein-free diet might be related to individual genetic differences. Therefore, studies conducted with large study groups could not provide statistically significant data to support this treatment option. Further studies should be conducted, especially in the field of genetics, in order to test our hypothesis.

Expression of Estrogen Receptor β in Hypothalamic Stem Cells

Neural stem cell activity at least partially accounts for the postweaning development of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and estrogen selectively mobilizes neural stem cells in the 3rd ventricle stem cell niche (3VSCN). Here, we examined the expression of estrogen receptor β (ERβ) in the SDN-POA and the 3VSCN. A subset of cells within the SDN-POA--delineated with or without calbindin D28K (CB28)-immunoreactivity (ir)--exhibited ERβ-ir. The ependymal cells that expressed nestin within the 3VSCN also expressed ERβ. Interestingly, a few proliferating (Ki67 positive) cells within the 3VSCN and the hypothalamic parenchyma, including the SDN-POA, displayed ERβ-ir. In parallel, a subset of cells in the subventricular zone was double-labeled with nestin and ERβ or Ki67 and ERβ while the subgranular zone exhibited few such double-labeled cells. ERβ is expressed in hypothalamic stem cells that may regulate cell regenerative cycles.

Facilitators and Barriers to Health Care Access among the Elderly in Tanzania: A Health System Perspective from Managers and Service Providers.

Tanzania is among the developing countries experiencing rapid growth of an ageing population, which has an implication in healthcare expenditure especially in resource poor settings where majority of elderly people cannot afford to pay for the cost of accessing health services. The country has developed the Tanzania National Health Policy (2007) and National Ageing Policy (2003), which, among other things, recognize the importance of having a healthcare system that provides free basic services to the vulnerable elderly population. This study aimed at exploring health service providers’ and managers’ perspectives on the factors facilitating or prohibiting access to health services among elderly people in Tanzania. The study adopted a qualitative approach and data were collected using semi-structured interviews. A total of 24 in-depth interviews were conducted with district healthcare managers, heads of public healthcare facilities, and health service providers. The data generated were analysed for themes and patterns. The results show that Tanzania’s healthcare system has made some efforts to implement the national exemption policy to ensure better access to health services for the elderly. Some of these efforts include: having in place a system to identify and exempt elderly people from paying for health services and giving them special priority during treatment. However, there are some barriers hindering elderly people’s access to health services. Among others include: lack of specific consultation rooms and doctors for serving the elderly, and lack of sufficient drugs and other medical equipment in most government-owned healthcare facilities. In summary, the healthcare system has created a good environment for the implementation of exemption policy aiming at enhancing accessibility of health services among the elderly population in the country. However, such environment cannot function effectively without addressing the identified barriers. It is recommended that the government should allocate adequate human and non-human resources to the healthcare system to enable it to function effectively, including the provision of health services to the elderly.

Changes in Statistics of Malignant Neoplasms of Central Nervous System Excluding Brain (ICD-10: C70, C72) In the Lower Silesia Region of Poland in the Years 2006-2012

Epidemiological data concerning malignant neoplasms of meninges and central nervous system parts other than brain in Poland are reported to many medical databases run by various institutions and are incongruent with each other which makes their practical interpretation highly difficult. Data on registered cases of malignant neoplasms of meninges (C70-C70.9 ICD-10) and of spinal cord, cranial nerves and parts of central nervous system other than brain (C72-C72.9 ICD-10) in the years 2006-2012, made available by public healthcare insurance provider Narodowy Fundusz Zdrowia in Lower Silesia region of Poland (NFZ) and data on new cases from Polish national neoplasms registry Krajowy Rejestr Nowotworow (KRN), were analyzed. The study revealed that those neoplasms are rare in Lower Silesia region of Poland population, number of new cases dropped in the analyzed period, but the NFZ/KRN cases ratio increased significantly especially in case of malignant neoplasms of central nervous system parts other than brain or meninges, which suggests big, and increasing with time, amount of medical procedures needed by those patients. It points at the need of respective adjustment of the level of public financing of treatment of malignant neoplasms of meninges and other central nervous system parts than brain. The study results indicate also that epidemiological reporting system in Poland shall be improved as there is growing number of Polish physicians who report mainly unspecific broad ICD-10 categories and there are year-to-year alternations of reported numbers of cases that do not have any explanation other than formal shifting in reported ICD-10 categories.

Frailty and the Immune System

Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.

Bacterial Meningitis Associated with Pituitary Macroadenoma: Systematic Review

Introduction Bacterial meningitis complicates rarely pituitary macroadenomas. The aim of our systematic review is to study the features of the association between bacterial meningitis and pituitary macroadenoma. Methods We conducted a literature search in both MedLine and Google Scholar database from 1967 to October 2016 and reviewed all cases described of the association between bacterial meningitis and pituitary macroadenoma apart from any surgical act and without pituitary apoplexy. Results We found 14 articles describing 16 patients aged of 22-69 years old with a male predominance (sex ratio 4.3). Two patients (12.5%) had a well-documented clinical history of pituitary macroadenoma prior to the diagnosis of bacterial meningitis. Rhinorrhea has been found as the most common symptom through six patients (37.5%). Through the CSF culture, bacterial meningitis among patients suffering of pituitary macroadenoma commonly was due to Streptococcus pneumoniae. The examination in 18.75% of cases revealed signs related to pituitary macroadenoma (ophthalmoplegia and blindness). Six patients (37.5%) had received a treatment by dopaminergic agonist alone and 4 patients (25%) were treated with dopaminergic agonist associated with surgical treatment. Surgical treatment consisted of closure of the osteomeningeal breach in 12.5% (2/16) and tumor resection in 31.25% (5/16). Three patients (18.75%) had benefited tumor resection without prior agonist treatment. The mortality was 12.5% (2/16). Conclusion Our systematic review shows that bacterial meningitis represents a rare initial symptom leading to the diagnosis of invasive pituitary macroadenoma.

A Systematic Review of Mexican American Elders with Type-2 Diabetes under Family Care of Medication Administration in Borderland

The prevalence of type-2 diabetes (T2DM) among Mexican-American older adults along the U.S.-Mexico border region is at epidemic proportions. Healthcare reform is trending toward long-term home-based management of chronic conditions. Under the Mexican cultural norm of familism, daily care for elders is also often provided by family caregivers whose competence levels may vary.  Adherence to the prescribed medication regimen is critical to attainment of optimal glucose control.  However, there is a startling lack of literature that addresses the link between family medication administration and care recipients’ health outcome.  This paper explores the role of culture in medication administration by family caregivers of elders with T2DM from the perspective of caregiver capabilities and caregiving demands. A critical review of the literature offers suggestions to guide future studies.

Supporting Quality Data Systems:  Lessons Learned from Early Implementation of Routine Viral Load Monitoring at a Large Clinic in Lilongwe, Malawi

Successful viral load programs rely on the presence of data systems and high quality of patient data. Using a cohort of 49 patients at Partners in Hope, a large, urban HIV clinic in Malawi, we performed a quality improvement assessment of a new viral load program with a focus on accuracy of data collected from patients as well as adherence to Malawi HIV Guidelines in regard to response to elevated viral loads (≥1,000 copies/mL). Data were obtained from three parallel medical record systems to investigate the proportion of patients with a repeat viral load and whether the three data systems agreed in regard to sociodemographic and clinical data. Fewer than 30% of patients had a repeat viral load within six months, as recommended in the Malawi HIV Guidelines. There were significant problems with data agreement across the three parallel databases used for care.  Date of birth was consistent for 55.1% (N=27) of patients, while a different date of birth was noted in all three sources for 10.2% of patients (N=5). Viral load data from all three sources agreed for only 2.0% of patients (N=1).  For 65.3% (N=32), the viral load from the laboratory did not match the recorded viral load in the electronic or paper record. Scale-up of viral load monitoring must be accompanied by the development of data systems that support workflow from sample collection to lab and back to provider. Education of providers and strategies for data collection with minimal errors can facilitate scale-up of high quality programs.

The Effect of HLA-DRB1 Allele Mismatch on the Results after Hematopoietic Stem Cell Transplantation

This article examines how HLA‑DRB1 allele mismatching influences outcomes after hematopoietic stem cell transplantation. It reviews graft‑versus‑host disease risk, engraftment, and survival metrics in the context of donor matching strategies. The findings support careful allele‑level typing to optimize donor selection and improve post‑transplant prognosis.

Dual Effects of Neuroprotection and Neurotoxicity by General Anesthetics on Neural Stem Cells: Role of Autophagy

General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis.

Emerging Paradigms in Regenerative Medicine: Stem cell Therapies

Stem cell research is now emerging as most exciting and promising area of modern biomedical research which has enormous potential for easing suffering for many diseases such as Parkinson’s, Alzheimer’s, Diabetes,Cancer and many more. This is now recognized most promising alternate therapeutic choice for some of the diseases which currently have no other option of an effective therapy. The Stem cell therapy is now strengthened by cutting- edge technologies and rigorous standards of clinical research thus rapidly progressed from bench to the clinic.

Human Umbilical Cord-Derived Mesenchymal Stem Cells as a Source of Odontoblasts: a GMP-compliant Approach

Stem cell-based regenerative therapy can be considered an innovative approach for curing dental caries. Pulp stem cells from human exfoliated deciduous teeth (SHEDs) represent a source of committed cells for generating odontoblasts in vitro; however, SHEDs are not easy to obtain and are limited in quantity. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered to be adult stem cells that can be easily obtained in large numbers. Here, SHEDs and UC-MSCs were conditioned in custom-made serum-free culture media in order to induce differentiation towards odontoblasts. SHEDs and UC-MSCs were expanded in vitro and differentiated into odontoblasts for 21 days using a medium containing transforming growth factor-β (TGF-b3), hepatocyte growth factor (HGF) and growth differentiation factor 5 (GDF5). The ability to induce odontoblast differentiation with a straightforward clinical protocol in compliance with good manufactoring practice (GMP), which avoids animal reagents, and uses unrelated stem cells of unrestricted availability, may be a first step towards a new innovative approach for dentin regeneration.

Immune Thrombocytopenia after Allogeneic Stem Cell Transplantation: Case Report and Brief Overview of Treatment Strategies

Immune thrombocytopenia (ITP) is a rare but well-recognized post-allogeneic hematopoietic stem cell transplant (HSCT) autoimmune complication for which a standard treatment approach is lacking. Herein we report on an adult patient affected by high-risk acute myeloid leukemia (AML) who developed a post-HSCT ITP. Due to the refractoriness to first-line therapies the patient underwent the thrombopoietin (TPO) mimetic Eltrombopag obtaining the ITP resolution. We also discuss the clinical course of ITP in post-HSCT setting and pros and cons of different therapeutic strategies, focusing on the emerging role of TPO mimetics.

Biocompatible Scaffolds for Human-Induced Pluripotent Stem Cell Transplantation and Modeling Post-Stroke Recovery in Three-Dimensional Neural Cell Culture

Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.

Localization of Angina Related Artery by Admission ECG in Unstable Angina and NSTEMI Patients

Objective: To find out the diagnostic accuracy of admission ECG against coronary angiography (CAG) to predict the ARA in patients with USAP /NSTEMI. Background: In USAP even though multiple active plaques are documented, one critical lesion would be responsible for the index episode of angina. Contrary to STEMI there is no standard methodology to identify the Angina related artery (ARA) in USAP.Therefore we plan to determine whether  admission  ECG could  predict the ARA  in patients with USAP/NSTEMI. Patients and Methods: 250 eligible patients with USAP/NSTEMI undergoing coronary angiography were enrolled in the study. After locating the ARA , the patient’s admission ECG  was compared with CAG finding  to study  whether  it has  any  predictive  value  for identifying  ARA. Results: Sensitivity of the admission ECG for LAD as ARA was 73.6%, Specificity was 93.5%, PPV was 90%, NPV was 81.8%, +LR 10.4, Posterior probability 0.89,  -LR 0.29, Posttest odds 0.22. Similarly for RCA and LCx ,Sensitivity was 63.1%, Specificity was 93.7%, PPV was 90.5%, NPV was 72.7%, +LR 9, Posterior Probability 0.89, -LR 0.35, Posttest odds 0.33. For the LM and TVD, Sensitivity was 66.6%, Specificity was 98.5%, PPV was 91.4%, and NPV was 92.5%, +LR 33, Posterior Probability 0.89, -LR 0.33, Posttest odds 0.08. Conclusion: With high +LR, Admission ECG is moderately sensitive and highly specific for detecting culprit artery.

Radical-Scavenging and Anti-Oxidative Activities of TBN in Cell-Free System and Murine H9c2 Cardiomyoblast Cells

Reactive oxygen species (ROS) and reactive nitrogen species are believed to be one of the most important culprits in the pathogenesis of cardio/cerebrovascular diseases. Intensive researches have been conducted to target free radicals as potential treatment for cardio/cerebrovascular diseases. The 2-(((1,1-dimethylethyl) oxidoimino)-methyl)-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has been demonstrated to exhibit significant therapeutic effects in ischemic stroke and Parkinson’s models due to its multiple functions, including calcium overload blockade and free radical-scavenging activity. In the present study, we found that TBN had significant radical trapping effect in cell-free assays. Additionally, TBN effectively blocked tert-butylhydroperoxide (t-BHP)-induced murine H9c2 cardiomyoblast cell death, suppressed H9c2 cell apoptosis and reversed the decrease in mitochondrial membrane potential. Furthermore, TBN markedly inhibited t-BHP-induced ROS generation and free radical NO and ONOO–.Taken together, these results suggest that TBN might be a potential candidate for the treatment of ischemic cardio/cerebrovascular diseases by targeting free radicals.

A Systematic Review of the use of Bupropion for Hypoactive Sexual Desire Disorder in Premenopausal Women

Objective: To assess the efficacy of bupropion therapy for hypoactive sexual desire disorder (HSDD) in women. Methods: A systematic review was performed utilizing the standard databases. Data were abstracted for study quality, characteristics, and outcomes. Due to the small number of studies and lack of consistently reported outcomes, a meta-analysis was not performed. Results: Two studies (289 women) met inclusion criteria. While one study had low risk of bias, the other had areas of high risk of bias. Both trials reported improvement in sexual function domains with treatment ranging from 12 weeks to 112 days. Conclusions: Despite two trials demonstrating benefit with bupropion treatment for premenopausal women with HSDD, the evidence is limited and not of adequate quality to recommend the therapy. More trials are needed in this area.

Evaluating Circadian Oscillators in Cancer Stem Cells

Cancer is influenced by the ability of cells to maintain circadian rhythms in molecular and metabolic processes. Disturbance of the underlying circadian timing mechanism in circadian clock cells leads to a higher frequency and more rapid progression of cancer. Cancer stem cells with properties of embryonic and somatic stem cells have been implicated as tumor initiators in several types of cancers. Although tumors are reported to have disorganized circadian rhythms, evidence of in vitro circadian rhythms in cancer stem cells of gliomas was recently presented. The possibility and consequences of circadian clocks functioning in cancer stem cells within tumors is examined, and the possible benefits to these cells from circadian timing is discussed in relation to cancer treatments.

Evaluating the Role and Efficacy of Plerixafor in Rescue Mobilization of Autologous Peripheral Blood Stem Cells

In autologous hematopoietic stem cell transplantation patients for whom granulocyte-colony stimulating factor fails to mobilize a sufficient number of peripheral blood stem cells, plerixafor proposes an option for successful rescue mobilization. This paper evaluates the efficacy of plerixafor to mobilize peripheral blood stem cells (PBSCs) in patients who failed previous mobilization with G-CSF alone, by retrospectively analysing the PBSC results from lymphoma and myeloma (MM) patients between 2006 and 2011. Patients were classified according to the CD34+ cells/kg yield collected by apheresis: < 2 x 106 CD34+ cells/kg was considered collection failure, whereas ≥ 5 x 106 CD34+ cells/kg was considered good mobilization. 797 patients underwent one or more apheresis. The first mobilization success rate was 82%; 140 patients proved to be poor mobilizers. Suboptimal first mobilization was significantly associated with age >50 years (p=0.005) and the absence of chemotherapy in prior PBSCs stimulation (p=0.04). 149 rescue protocols were used in the 140 poor mobilizers, and 71 patients received plerixafor. In univariate analysis the remobilization rate without plerixafor was 42% and increased to 65% when plerixafor was added. In multivariate analysis, plerixafor administration reduced the PBSC remobilization failure risk by a half (OR=0.47). The median value of CD34+ cells/kg in transplants increased from 1.43 (range, 014.03) without plerixafor to 3.85 (range, 0–18.25; p=1 x 10-4) with plerixafor. There were more good mobilizers after plerixafor use (35% with plerixafor versus 15% without plerixafor; p=0.005). Plerixafor efficacy was similar for lymphoma (60% remobilization) and MM (80%; p=0.12). These data show that plerixafor was effective in poor mobilizers and that it synergized with G-CSF to improve the quantity of collected PBSCs. Plerixafor also increased transplant feasibility by 23%. While the clinical results of this study are promising, economic data were not taken into account and there is a need for real work concerning the cost-effectiveness of this treatment. We propose a subsequent study in which the economic efficacy of plerixafor’s use is evaluated based on the financial aspects of the treatments received by the cohort evaluated in this paper.

Laryngeal Tissue Engineering using Rabbit Adipose Derived Stem Cells in Fibrin: A Pre-Clinical Model

Vocal fold scarring is a clinical problem without reliable treatment. Tissue engineering of a vocal fold replacement is an exciting potential treatment for vocal fold scars that involve multiple layers of the vocal fold. Human adipose-derived stem cells (ASC) were previously used to produce a promising vocal fold cover layer replacement. However, relevant in vivo studies are needed before human application, and implanting the human cells in animal larynges would introduce significant risk and data confounding. We therefore report here the development of a construct based on rabbit ASC with the potential for use in pre-clinical implantation studies. Rabbit ASC were isolated and cultured in a three-dimensional fibrin matrix to create an implantable construct resembling the vocal fold mucosa. Key differences between the human cell and the rabbit cell models are highlighted.

Diagnostics of Progressive Multifocal Leukoencephalopathy in a Patient with Concomitant Lymphoma Infiltration of Central Nervous System During R-CHOP Chemotherapy- A Case Presentation and Review of the Literature.

Progressive multifocal leukoencephalopathy (PML) is a rare complication associated, inter alia, with rituximab-based lymphoma treatment. PML diagnosis is made easier with the criteria recently published by the American Academy of Neurology. Unambiguous diagnosis of PML can be achieved by demonstration of the histopathological triad comprising:(1) demyelination, (2) bizarre astrocytes and (3) enlarged oligodendroglial nuclei together with detection of viral particles by electron microscopy. However, symptoms of PML may be similar to those observed during lymphoma progression into the central nervous system (CNS). Here we report the case of a patient with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP who developed clinical signs indicating PML. Intravital diagnostic methods failed to yield an unequivocal diagnosis of PML or lymphoma progression in the CNS. However, a post-mortem examination of brain biopsy specimens performed by electron microscopy demonstrated lesions typical for PML and the presence of viral particles. In addition, immunohistochemical assays identified a massive infiltration of lymphoma cells. The case thus suggests either the extremely rare coexistence of two complications: lymphoma CNS infiltration and PML or induction structural CNS lesions by lymphoma infiltration indistinguishable from PML. The presented findings thus highlight the need for a further review of the current diagnostic criteria for PML.

Evaluation of SterculiaUrens Gum as Novel Carrier for Oral Colon Targeted Drug Delivery System

The purpose of the research is to evaluate Sterculiaurens gum as a carrier for oral colon targeted drug delivery system. Sterculia gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent and as a controlled release polymer, but it has not been exploited as colon targeting carrier. For evaluation as a carrier for colonic delivery of drugs characterization of gum was done. Microflora degradation studies of gum were conducted in phosphate buffer solution (PBS) pH 7.4 containing rat caecal content under anaerobic environment. Solubility, swelling index, viscosity and pH of the polymer solution were determined. Different formulation aspects considered were: gum concentration (10–40%), concentration of citric acid (10–30 %) on swelling index and in-vitro drug release. The results of the isothermal stress testing (IST) shows no degradation of samples of model drug, azathioprine, in the drug polymer mixture and the core tablet excipients. DSC and FT-IR study has proved the compatibility of the drug with Sterculia gum and other tablet excipients. Microflora degradation study revealed that Sterculia gum can be used as tablet excipient for drug release in the colonic region by utilizing the action of enterobacteria. Sterculia gum exhibits premature drug release in the upper GIT without enteric coating and may not reach to the colonic region. From the study, Sterculia gum as colon targeting carrier is possible via coating with chitosan/Eudragit mixed blend polymers which would provide acid as well as intestinal resistance; but undergo enzymatic degradation once it reaches the colon.

Cardiac Mechanics in Patients with Systemic Hypertension with Normal EF: A Speckle - Strain Imaging Study

Background: Conventional transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) are usually unable to reveal very early subtle abnormalities in left ventricular (LV) systolic function caused by hypertension, prior to manifestation of hypertrophy (LVH). This study was undertaken to assess whether speckle tracking echocardiography (STE) provides more insight into early hypertension induced LV systolic dysfunction, with the purpose of identifying patients at higher risk for heart failure (HF). Methods: Fifty patients (54.16 ± 8.4 years) and 50 controls (52.17 ± 8.6 years) were enrolled. According to the presence or absence of LVH, patients were classified as LVH(+) and LVH(–), respectively. Global longitudinal function was calculated by TDI, global strains (longitudinal (LS), radial (RS), and circumferential (CS)) were assessed by STE. Results: Conventional TTE showed a normal systolic function in all patients. TDI was able to detect a systolic dysfunction only in the LVH(+) group (P < 0.001) whereas STE revealed an impairment of systolic LS and CS in all patients, including those without hypertrophy (P =<0.0001). Furthermore, in the LVH(+) group, STE showed increased RS . Conclusion: In hypertensive patients, STE provides more detailed information than conventional echocardiography and TDI, since it reveals a systolic dysfunction before hypertrophy occurs (Stage A of ACC/AHA classification of HF) and identifies some early LV mechanic changes that might improve the clinical management of these patients

High-Throughput Complex Disease Modeling for Ethical Drug Discovery: Clinical Relevance of a NAM Platform for Cancer Biomarker Development

The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.