Search

Abstract Background and objectives Although the goal of translational research is to bring biomedical knowledge from the laboratory to clinical trial and therapeutic products for improving health, this goal has not been well achieved as often as desired because of many barriers documented in different countries. Therefore, the aim of this study was to investigate the challenges and opportunities of translating animal research into human trials in Ethiopia. Methods A descriptive qualitative study, using in-depth interviews, was conducted in which preclinical and clinical trial researchers who have been involved in animal research or clinical trials as principal investigator were involved. Data were analyzed using inductive thematic process. Results Six themes were emerged for challenges: lack of financial and human capacity, inadequate infrastructure, operational obstacles and poor research governance, lack of collaboration, lack of reproducibility of results and prolonged ethical and regulatory approval processes. Furthermore, three themes were synthesized for opportunities: growing infrastructure and resources, improved human capacity and better administrative processes and initiatives for collaboration. Conclusion and recommendations The study found that the identified characteristics/features are of high importance either to hurdle or enable the practice of translating animal research into human trials. The study suggests that there should be adequate infrastructure and finance, human capacity building, good research governance, improved ethical and regulatory approval process, multidisciplinary collaboration, and incentives and recognition for researchers to overcome the identified challenges and allow translating of animal research into human trials to proceed more efficiently.

Currently, studies conducted on animal models provide new insight into the aetiology and course of various pathological conditions in humans. Due to the cause of disease, animal models can be divided into two categories: natural models, such as nude mice, and induced models, such as transgenic pigs. This article discusses several examples of animal models and their contributions to the development of effective therapies for human diseases such as muscular dystrophy, cystic fibrosis, and atherosclerosis. In addition, we presented the latest news on gene therapy, xenotransplantation, and drug trials in humans and animals. [ABSTRACT FROM AUTHOR]

Background and objectives: Although the goal of translational research is to bring biomedical knowledge from the laboratory to clinical trial and therapeutic products for improving health, this goal has not been well achieved as often as desired because of many barriers documented in different countries. Therefore, the aim of this study was to investigate the challenges and opportunities of translating animal research into human trials in Ethiopia. Methods: A descriptive qualitative study, using in-depth interviews, was conducted in which preclinical and clinical trial researchers who have been involved in animal research or clinical trials as principal investigator were involved. Data were analyzed using inductive thematic process. Results: Six themes were emerged for challenges: lack of financial and human capacity, inadequate infrastructure, operational obstacles and poor research governance, lack of collaboration, lack of reproducibility of results and prolonged ethical and regulatory approval processes. Furthermore, three themes were synthesized for opportunities: growing infrastructure and resources, improved human capacity and better administrative processes and initiatives for collaboration. Conclusion and recommendations: The study found that the identified characteristics/features are of high importance either to hurdle or enable the practice of translating animal research into human trials. The study suggests that there should be adequate infrastructure and finance, human capacity building, good research governance, improved ethical and regulatory approval process, multidisciplinary collaboration, and incentives and recognition for researchers to overcome the identified challenges and allow translating of animal research into human trials to proceed more efficiently. [ABSTRACT FROM AUTHOR]

Abnormal glucose homeostasis is associated with metabolic syndromes including cardiovascular diseases, hypertension, type 2 diabetes mellitus, and obesity, highlighting the significance of maintaining a balanced glucose level for optimal biological function. This highlights the importance of maintaining normal glucose levels for proper biological functioning. Sulforaphane (SFN), the primary bioactive compound in broccoli from the Cruciferae or Brassicaceae family, has been shown to enhance glucose homeostasis effectively while exhibiting low cytotoxicity. This paper assesses the impact of SFN on glucose homeostasis in vitro, in vivo, and human trials, as well as the molecular mechanisms that drive its regulatory effects. New strategies have been proposed to enhance the bioavailability and targeted delivery of SFN in order to overcome inherent instability. The manuscript also covers the safety evaluations of SFN that have been documented for its production and utilization. Hence, a deeper understanding of the favorable influence and mechanism of SFN on glucose homeostasis, coupled with the fact that SFN is abundant in the human daily diet, may ultimately offer theoretical evidence to support its potential use in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Introduction: This review synthesizes the available evidence pertinent to the effect of platelet-rich fibrin on the rate of orthodontic tooth movement during comprehensive orthodontic treatment. Method: This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Nine electronic databases were searched until January 2024 without restrictions, followed by a hand search of the reference lists. Controlled randomized split-mouth human studies assessing the effect of platelet-rich fibrin on the rate of orthodontic tooth movement were included. All relevant data from the included studies were extracted and pooled for qualitative and quantitative analysis. Risk-of-Bias was assessed using the Cochrane Risk of Bias tool. The certainty of the evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results: From 515 studies, eleven randomized clinical trials were included for qualitative analysis and nine for quantitative analysis. The certainty of the evidence for these studies was low to moderate. The overall risk of bias for most studies was of some concern. The pooled estimate of the data from ten studies has a mean revealed difference of 1.31 (0.13–2.48) at a 95 % confidence interval with significant heterogeneity. Conclusions: This systematic review suggest that platelet-rich fibrin enhances the orthodontic tooth movement rate, but the evidence quality was moderate. Further, based on the currently available evidence, the effectiveness of platelet-rich fibrin on the acceleration of orthodontic tooth movement could not be fully established. Trial registration: PROSPERO: (CRD42021261836).

This review synthesizes the available evidence pertinent to the effect of platelet-rich fibrin on the rate of orthodontic tooth movement during comprehensive orthodontic treatment. This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Nine electronic databases were searched until January 2024 without restrictions, followed by a hand search of the reference lists. Controlled randomized split-mouth human studies assessing the effect of platelet-rich fibrin on the rate of orthodontic tooth movement were included. All relevant data from the included studies were extracted and pooled for qualitative and quantitative analysis. Risk-of-Bias was assessed using the Cochrane Risk of Bias tool. The certainty of the evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation tool. From 515 studies, eleven randomized clinical trials were included for qualitative analysis and nine for quantitative analysis. The certainty of the evidence for these studies was low to moderate. The overall risk of bias for most studies was of some concern. The pooled estimate of the data from ten studies has a mean revealed difference of 1.31 (0.13–2.48) at a 95 % confidence interval with significant heterogeneity. This systematic review suggest that platelet-rich fibrin enhances the orthodontic tooth movement rate, but the evidence quality was moderate. Further, based on the currently available evidence, the effectiveness of platelet-rich fibrin on the acceleration of orthodontic tooth movement could not be fully established. PROSPERO: (CRD42021261836). [Display omitted] [ABSTRACT FROM AUTHOR]

AbstractCardiovascular diseases are a major global cause of death and healthcare costs, emphasizing the need for effective prevention and management of cardiometabolic risk factors. One promising approach is the consumption of technologically processed functional foods enriched/fortified with (poly)phenols. The current systematic review aimed to evaluate the human clinical trials evidence on the effect of intake of these foods on reducing the most common cardiometabolic risk factors. 12 randomized controlled studies were included in the systematic review, with varying food intake amounts (27–360 g/day) and (poly)phenol doses (32.5–850 mg/day). These interventions included consumption of functional bakery goods, cereal bars, pasta, chocolate, and yogurt, with supplementation periods spanning from 2 to 52 wk. Several foods, such as green tea extract-fortified rye bread and olive fruit (poly)phenol-fortified yogurt, significantly lowered blood pressure. Flavonoid-enriched chocolate, hydroxytyrosol-fortified bread, and other products influenced glucose metabolism. Additionally, various functional foods were associated with improved blood lipid levels. While these results indicate the health advantages of consuming technologically processed functional foods enriched/fortified with (poly)phenols, caution is warranted due to the scarcity and limitations of existing studies. Further research is needed to confirm and expand upon these results in the prevention and management of cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

The main aim of this study is to validate the Joint system thermoregulation model (JOS-3 model) for the male population living in tropical climates and to analyze the effect of environmental conditions and physical activities on human thermal comfort. For this, a MATLAB code of the JOS-3 thermoregulation model was developed and verified with experimental data available in the literature. Further, the human trials were conducted in the study under three different scenarios with Indian participants to check the validity of the JOS-3 model for the population living in tropical climates. It was observed that the JOS-3 model could appropriately predict the physiological responses of people living in tropical climates. Additionally, findings from the parametric study show that the mean skin and core temperatures increase as the ambient temperature, relative humidity (RH), and physical activity increase. Besides, the skin temperature is most affected by the ambient temperature, followed by physical activity and RH. On the other hand, the core temperature is most affected by physical activity, followed by the ambient temperature and RH. When physical activity increased from 1.2 to 3.8 MET, mean skin and core temperatures increased by 6.6% and 4.5%, respectively, after 60 min at 38°C, 70% RH, and 0.31 clo. [ABSTRACT FROM AUTHOR]

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation. [ABSTRACT FROM AUTHOR]

Valvular heart disease is a common disease often necessitating valve replacement. Mechanical heart valves (MHVs) are often used in younger patients because of their longer durability. Their main disadvantage is the need for lifelong anticoagulation. Warfarin is considered a standard treatment, but it is far from perfect. Direct oral anticoagulants (DOACs) are a new and more patient-friendly alternative to warfarin when anticoagulation is required, but have not yet been approved for the indication of mechanical valves. Evidence acquisition: A literature search of Pubmed, Embase, Web of Science (Core Collection), and Cochrane Library (from inception to May 2023) was performed using a search string that was well defined and not modified during the study. An extensive overview of the search terms used in each database can be found in the Appendix. Only prospective clinical trials were included in this review. A total of 10 publications were included in this review. Relevance to clinical practice: This systematic review summarizes the different types of DOACs and their possible use in the anticoagulation of mechanical valves. We aim to propose future directions in anticoagulation research for mechanical valves. Conclusions: DOAC use in MHVs has been halted due to the failure of both dabigatran and apixaban in two major clinical trials. However, rivaroxaban was successful in two small clinical trials. Ample research is still needed to explore new valve designs as well as new anticoagulation targets. [ABSTRACT FROM AUTHOR]

Cohorts of healthy younger adults (18–50yrs) and healthy older adults (60–75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses. [ABSTRACT FROM AUTHOR]

The hypothalamic–pituitary–adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required. [ABSTRACT FROM AUTHOR]

We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period (p = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab. [ABSTRACT FROM AUTHOR]

The definition of immune tolerance to allogeneic tissue and organ transplants in laboratory animals and humans continues to be the acceptance of the donor graft, rejection of third-party grafts, and specific unresponsiveness of recipient immune cells to the donor alloantigens in the absence of immunosuppressive treatments. Actively acquired tolerance was achieved in mice more than 60 years ago by the establishment of mixed chimerism in neonatal mice. Once established, mixed chimerism was self-perpetuating and allowed for acceptance of tissue transplants in adults. Successful establishment of tolerance in humans has now been reported in several clinical trials based on the development of chimerism after combined transplantation of hematopoietic cells and an organ from the same donor. This review examines the mechanisms of organ graft acceptance after establishment of mixed chimerism (allo-tolerance) or complete chimerism (self-tolerance), and compares the development of graft versus host disease (GVHD) and graft versus tumor (GVT) activity in complete and mixed chimerism. GVHD, GVT activity, and complete chimerism are also discussed in the context of bone marrow transplantation to treat hematologic malignancies. The roles of transient versus persistent mixed chimerism in the induction and maintenance of tolerance and organ graft acceptance in animal models and clinical studies are compared. Key differences in the stability of mixed chimeras and tolerance induction in MHC matched and mismatched rodents, large laboratory animals, and humans are examined to provide insights into the safety and efficacy of translation of results of animal models to clinical trials. [ABSTRACT FROM AUTHOR]

The definition of immune tolerance to allogeneic tissue and organ transplants in laboratory animals and humans continues to be the acceptance of the donor graft, rejection of third-party grafts, and specific unresponsiveness of recipient immune cells to the donor alloantigens in the absence of immunosuppressive treatments. Actively acquired tolerance was achieved in mice more than 60 years ago by the establishment of mixed chimerism in neonatal mice. Once established, mixed chimerism was self-perpetuating and allowed for acceptance of tissue transplants in adults. Successful establishment of tolerance in humans has now been reported in several clinical trials based on the development of chimerism after combined transplantation of hematopoietic cells and an organ from the same donor. This review examines the mechanisms of organ graft acceptance after establishment of mixed chimerism (allo-tolerance) or complete chimerism (self-tolerance), and compares the development of graft versus host disease (GVHD) and graft versus tumor (GVT) activity in complete and mixed chimerism. GVHD, GVT activity, and complete chimerism are also discussed in the context of bone marrow transplantation to treat hematologic malignancies. The roles of transient versus persistent mixed chimerism in the induction and maintenance of tolerance and organ graft acceptance in animal models and clinical studies are compared. Key differences in the stability of mixed chimeras and tolerance induction in MHC matched and mismatched rodents, large laboratory animals, and humans are examined to provide insights into the safety and efficacy of translation of results of animal models to clinical trials.

Cerebrovascular diseases are the second leading cause of death worldwide. Despite significant research investment, the only available therapeutic options are mechanical thrombectomy and tissue plasminogen activator thrombolysis. None of the more than a thousand drugs tested on animal models have proven successful in human clinical trials. Several factors contribute to this poor translation of data from stroke-related animal models to human stroke patients. Firstly, our understanding of the molecular and cellular processes involved in recovering from an ischemic stroke is severely limited. Secondly, although the risk of stroke is particularly high among older patients with comorbidities, most drugs are tested on young, healthy animals in controlled laboratory conditions. Furthermore, in animal models, the tracking of post-stroke recovery typically spans only 3 to 28 days, with occasional extensions to 60 days, whereas human stroke recovery is a more extended and complex process. Thirdly, young animal models often exhibit a considerably higher rate of spontaneous recovery compared to humans following a stroke. Fourth, only a very limited number of animals are utilized for each condition, including control groups. Another contributing factor to the much smaller beneficial effects in humans is that positive outcomes from numerous animal studies are more readily accepted than results reported in human trials that do not show a clear benefit to the patient. Useful recommendations for conducting experiments in animal models, with increased chances of translatability to humans, have been issued by both the STEPS investigative team and the STAIR committee. However, largely, due to economic factors, these recommendations are largely ignored. Furthermore, one might attribute the overall failures in predicting and subsequently developing effective acute stroke therapies beyond thrombolysis to potential design deficiencies in clinical trials. [ABSTRACT FROM AUTHOR]

Background: The influence of different biological agents on the rate of orthodontic tooth movement (OTM) has been extensively reviewed in animal studies with conflicting results. These findings cannot be extrapolated from animals to humans. Therefore, we aimed to systematically investigate the most up-to-date available evidence of human studies regarding the effect of the administration of different biological substances on the rate of orthodontic tooth movement. Methods: A total of 8 databases were searched until the 16th of June 2020 without restrictions. Controlled randomized and non-randomized human clinical studies assessing the effect of biological substances on the rate of OTM were included. ROBINS-I and the Cochrane Risk of Bias tools were used. Reporting of this review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 11 studies (6 randomized clinical trials and 5 prospective clinical trials) were identified for inclusion. Local injections of prostaglandin E1 and vitamin C exerted a positive influence on the rate of OTM; vitamin D showed variable effects. The use of platelet-rich plasma and its derivatives showed inconsistent results, while the local use of human relaxin hormone showed no significant effects on the rate of OTM. Limitations: The limited and variable observation periods after the administration of the biological substances, the high and medium risk of bias assessment for some included studies, the variable concentrations of the assessed biological agents, the different experimental designs and teeth evaluated, and the variety of measurement tools have hampered the quantitative assessment of the results as originally planned. Conclusions and implications: Despite the methodological limitations of the included studies, this systematic review provides an important overview of the effects of a variety of biological agents on the rate of tooth movement and elucidates the deficiencies in the clinical studies that have been conducted so far to evaluate the effectiveness of these agents in humans, providing some guidelines for future robust research. Trial registration: PROSPERO (CRD42020168481, www.crd.york.ac.uk/prospero) [ABSTRACT FROM AUTHOR]

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.

Manu Goyal,1 Anil Chauhan,2 Vishavdeep Goyal,3 Nishant Jaiswal,1,2 Shreya Singh,4 Meenu Singh1,2 1Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 2Indian Council of Medical Research Advanced Centre for Evidence Based Child Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 3Apollo Hospitals International Limited, Ahmedabad, India; 4Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Abstract: The unprecedented epidemic spread of chikungunya worldwide illustrates the critical need for potent vaccines and therapeutic interventions. The morbidity and mortality associated with this arboviral infection has become a major public health problem in many countries across different continents. Increasing public–private partnerships have opened new avenues in research and development of vaccines. This review mainly focuses on the recent advances in patented approaches for chikungunya vaccine development and the forthcoming challenges. Keywords: chikungunya, epidemics, CHIKV vaccine candidates, clinical trials, humans

Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. Fifty-four apparently healthy abdominally obese (waist circumference: 102–110 cm) and 25 normal-weight men (waist circumference: <94 cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102 cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6 g fat) and 300 mL low-fat milk. The mean weight loss was 10.3 kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89 ± 2.52 versus 0.48 ± 2.50 percentage points; P = 0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P = 0.028), insulin (P = 0.029) and C-peptide concentrations (P < 0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401. [ABSTRACT FROM AUTHOR]

Edible flowers have been used for their therapeutic properties for ancient times. Many sources indicate, that edible flowers have many beneficial activities like anti-anxiety, anti-cancer, anti-diabetic, anti-inflammatory, antioxidant, diuretic, anthelmintic, immunomodulatory and anti-microbial. People use it also in culinary applications, because they improve the aesthetic value, taste, flavour and appearance of dishes. This study expands knowledge on the content and composition of low molecular phytochemicals of edible flowers and the pro-healthy activities of their extracts or preparations. It is focused on showing flowers which are the best sources of individual compounds and on recent findings with the use of flower extracts or preparations in various cell-lines, animal and human models. Performed comparison of composition includes simple phenolic acids, flavonols, flavanols, flavons, anthocyanidins, carotenoids and tocols. Species with the highest content of selected compounds are highlighted. Unique components of some flowers such as crocin, nimbolide, oleanic and ursolic acids, and acteoside are also mentioned. The potential activity of edible flowers for human health was analysed based on in vitro models with the use of various cell-lines and in vivo models with animal (mostly mice and rat) and human trials. The majority of the reviewed studies confirm the pro-healthy activity of edible flowers or their extracts. Image 1 • Edible flowers are valuable and rich source of many phytochemicals. • Flowers unique compounds are nimbolide, crocin, acteoside, oleanic and ursolic acids. • Flower extracts show a wide array of health promoting properties in vivo. • Crocin have efficiency in treatment people with depression. • Further attention towards in vivo properties of edible flowers is needed. [ABSTRACT FROM AUTHOR]

There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead. [ABSTRACT FROM AUTHOR]

Interactions between polyphenols and gut microbiota are indeed a major issue of current interest in food science research. Knowledge in this subject is progressing as the experimental procedures and analysis techniques do. The aim of this article is to critically review the more leading‐edge approaches that have been applied so far in the study of the interactions between grape/wine polyphenols and gut microbiota. This is the case of in vitro dynamic gastrointestinal simulation models that try to mitigate the limitations of simple static models (batch culture fermentations). More complex approaches include the experimentation with animals (mice, rats, pigs, lambs and chicks) and nutritional intervention studies in humans. Main advantages and limitations as well as the most relevant findings achieved by each approach in the study of how grape/wine polyphenols can modulate the composition and/or functionality of gut microbiota, are detailed. Also, common findings obtained by the three approaches (in vitro, animal models and human nutritional interventions) such as the fact that the Firmicutes/Bacteroidetes ratio tends to decrease after the feed/intake/consumption of grape/wine polyphenols are highlighted. Additionally, a nematode (Caenorhabditis elegans) model, previously used for investigating the mechanisms of processes such as aging, neurodegeneration, oxidative stress and inflammation, is presented as an emerging approach for the study of polyphenols interacting gut microbiota. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60 ± 8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10 g of refined cold-pressed flaxseed oil, providing 4.7 g ALA (n = 29), or 10 g of high-oleic sunflower (control) oil (n = 30) for 12 weeks. As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58 μmol/L (P = 0.02) and 0.14 pg/mL (P = 0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. A high intake of ALA, about 3–5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals. [ABSTRACT FROM AUTHOR]

The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions. [ABSTRACT FROM AUTHOR]

To compare the effects of thermoelectric cooling and ventilation clothing (TCVC) and traditional hybrid cooling clothing (PCM-Fans cooling, HCC) on human thermal physiology, cooling power, and cognitive abilities in high-temperature environments, both human thermo-physiological and thermal manikin tests were carried out. The physiological parameters (heart rate, ear temperature, skin temperature), subjective questionnaires (overall thermal sensation, thermal comfort, wet sensation), and cognitive ability evaluation of 12 subjects were collected. The thermal manikin was used to quantify the cooling efficiency and the building energy reduction of TCVC. As a result, it was found that the mean skin temperature of TCVC and HCC was reduced by 1.6 °C and 1.1 °C compared to no cooling (CON), and the sweat evaporation rate was 57.98% and 54.6%, respectively. Compared with HCC, TCVC is consistently rated with the lowest thermal sensation, lowest wet sensation, and highest thermal comfort. Moreover, TCVC demonstrates superior performance in continuous cooling effect and humidity regulation performance, making it suitable for long-term cooling requirements(≥2h) compared with HCC. In addition, TCVC provided a cooling power of 80.88W/kg, which was 1.8 times higher than HCC (45.38W/kg), indicating that TCVC had a superior cooling efficiency. We found that using TCVC can increase the HVAC temperature set point by 5 °C and save about 20∼55% of building energy. This study supports the use of cooling technology and guides users to select appropriate cooling garments for different scenarios. • TCVC offers stable and enduring cooling, while HCC is more aggressive within short time. • TCVC enhances humidity regulation, achieving a 58% sweat evaporation rate. • TCVC provides 80.9W/kg cooling power, which is 1.8 times that of HCC (45.4W/kg). • Applying TCVC raises the HVAC temperature set point by 5 °C, promising substantial energy savings. [ABSTRACT FROM AUTHOR]

Purvish Mahendra ParikhBrain-computer interfaces are becoming a tangible reality, capable of significantly aiding patients in real-world scenarios. The recent approval by the U.S. Food and Drug Administration for clinical human trials of Neuralink marks a monumental stride, comparable to Mr. Armstrong's moonwalk. Numerous other companies are also pioneering innovative solutions in this domain. Presently, over 150,000 patients in the United States possess brain implants. As technology advances, it holds the potential to alleviate various conditions, notably motor paralysis, cerebral palsy, and involuntary movements., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

A high protein content combined with its enormous growth capacity make duckweed an interesting alternative protein source, but information about postprandial responses in humans is lacking. The present study aimed to assess the postprandial serum amino acid profile of Lemna minor in healthy adults in comparison with green peas. A secondary objective was to obtain insights regarding human safety. A total of twelve healthy volunteers participated in a randomised, cross-over trial. Subjects received two protein sources in randomised order with a 1-week washout period. After an overnight fast, subjects consumed L. minor or peas (equivalent to 20 g of protein). After a baseline sample, blood samples were taken 15, 30, 45, 60, 75, 90, 120, 150 and 180 min after consumption to assess amino acid, glucose and insulin levels. Heart rate, blood pressure and aural temperature were measured before and after consumption, and subjects reported on gastrointestinal discomfort for four subsequent days. Compared with green peas, significantly lower blood concentrations of amino acids from L. minor were observed, indicating lower digestibility. L. minor consumption resulted in lower plasma glucose and insulin levels compared with peas, probably due to different glucose content. There were no significant differences concerning the assessed health parameters or the number of gastrointestinal complaints, indicating that a single bolus of L. minor – grown under controlled conditions – did not induce acute adverse effects in humans. Further studies need to investigate effects of repeated L. minor intake and whether proteins purified from L. minor can be digested more easily.

Cardiovascular diseases are a major global cause of death and healthcare costs, emphasizing the need for effective prevention and management of cardiometabolic risk factors. One promising approach is the consumption of technologically processed functional foods enriched/fortified with (poly)phenols. The current systematic review aimed to evaluate the human clinical trials evidence on the effect of intake of these foods on reducing the most common cardiometabolic risk factors. 12 randomized controlled studies were included in the systematic review, with varying food intake amounts (27-360 g/day) and (poly)phenol doses (32.5-850 mg/day). These interventions included consumption of functional bakery goods, cereal bars, pasta, chocolate, and yogurt, with supplementation periods spanning from 2 to 52 wk. Several foods, such as green tea extract-fortified rye bread and olive fruit (poly)phenol-fortified yogurt, significantly lowered blood pressure. Flavonoid-enriched chocolate, hydroxytyrosol-fortified bread, and other products influenced glucose metabolism. Additionally, various functional foods were associated with improved blood lipid levels. While these results indicate the health advantages of consuming technologically processed functional foods enriched/fortified with (poly)phenols, caution is warranted due to the scarcity and limitations of existing studies. Further research is needed to confirm and expand upon these results in the prevention and management of cardiometabolic risk factors.

Several epidemiological studies associated the consumption of wine with the reduction of the risk factors for cardiovascular disease and certain cancers, as well as for diabetes. These conditions are characterized by inflammatory mechanisms in addition to other biological mechanisms. Acute and chronic inflammation is mediated by a plethora of biomarkers production and pathway activation. Since the health promoting properties of wine in different pathological conditions may include the reduction of inflammation, the aim of this paper was to collect and review the in vitro, in vivo, and human studies performed to evaluate the effects of wine on different models of inflammation. Although great variability in wine intake, period of consumption, and content of phenolic compounds was observed, data from both human and animal studies showed a positive modulation of inflammatory biomarkers (cytokines, coagulation parameters) and oxidative stress (mainly malondialdehyde) involved in cardiovascular function. In addition, some convincing evidence was obtained in different models suggesting a positive modulation of risk factors for gastric and intestinal inflammation. Contradictory results were obtained for metabolic syndrome and type 2 diabetes. To date, no significant paper has been published in the area of immune function. Integrating in vivo data and in vitro studies, the NF-κ B pathway has been identified as a critical target for the protective properties of a moderate wine consumption. [ABSTRACT FROM AUTHOR]

Adaptive (or thermoregulatory model controlled) manikins are useful in quantifying thermal exchanges of the human-clothing-environment system and in simulating human thermophysiological behaviours. Current existing adaptive manikins didn’t take account into the body movement/posture during simulations and this may greatly affect the precision of simulation results. Hence, in this study, the impact of body movement on human physiological responses was investigated using a ‘Newton’ type adaptive thermal manikin and human subjects in a warm environment (i.e., T a  = 30.0 ± 0.5 °C, RH = 60 ± 5%, v a  = 0.17 ± 0.05 m/s). Results demonstrated that the body movement significantly affected the thermal exchange between the clothed manikin and its surrounding environment. Significantly greater mean skin and core temperatures were noted on the standing manikin than those on the walking manikin. In contrast, simulation results obtained from the walking manikin were much closer to human trial data than those obtained from the standing adaptive manikin. Particularly, no significant difference was found in the mean core temperature between the walking adaptive manikin and human subjects. Therefore, the standing adaptive manikin significantly overestimated thermal stress for the two studied conditions. It was thus suggested the body movement should be considered when mimicking human activities on adaptive manikins. [ABSTRACT FROM AUTHOR]

Creation of adhesions in digital flexor tendons after repairing remains a major problem in hand surgery. The adhesions are part of the healing process and produce almost inevitably functional disability following the biological response after tendon injury. To achieve better gliding function of the digital tendons by reducing peritendinous adhesions without adversely affecting the healing process itself, several options, both surgical and pharmacological have been explored. Attempts at reducing postoperative adhesion formation have included early postoperative rehabilitation, low-friction surgical repair techniques, pharmacological antiadhesive reagents, and the use of physical barriers to adhesion formation. Level of Evidence: Not ratable. [ABSTRACT FROM AUTHOR]

In this study, a novel smart electrically heated sleeping bag was developed by incorporating a proportional–integral–derivative heating control system into a traditional sleeping bag. The smart sleeping bag was aimed to maintain human feet temperature within the thermoneutral range (i.e. 25.0–34.0℃) by automatically adjusting the heat power to the feet region based on real-time human toe temperatures. Subsequently, the performance of the newly developed smart sleeping bag in improving human thermal comfort was investigated by human trials. Eight female subjects underwent two 8-hour sleep trials, that is, the smart sleeping bag with power turned on (SleepingbagHT) and the smart sleeping bag with power turned off (SleepingbagCON). All trials were performed at an air temperature of 6.1 ± 0.5℃ (i.e. the EN 13537 defined comfort temperature for females), relative humidity of 80 ± 5% and air velocity of 0.4 ± 0.1 m/s. It was found that SleepingbagHT could maintain both the foot and toe temperatures within the thermal neutral range as well as keep the local-, and whole-body thermal and comfort sensations in thermal neutral state throughout the 8-hour cold exposure. In contrast, linearly decreasing foot and toe temperatures and aggravated local-, and whole-body thermal and comfort sensations were detected in SleepingbagCON within a 4.5-hour cold exposure. It could thus be concluded that the smart electrical heating sleeping bag was able to provide wearers an 8-hour comfortable sleep in the studied cold environment. [ABSTRACT FROM AUTHOR]

Recent experimental and clinical studies suggest that consumption of blueberry products has potential health benefits in ameliorating the development of obesity and its related comorbidities, including type 2 diabetes (T2D) and chronic inflammation. Blueberry fruits are enriched with numerous bioactive components such as vitamins, phenolic acid and anthocyanins which could contribute to these protective effects. Possible mechanisms by which blueberries exert their beneficial properties include counteracting oxidative stress, regulating glucose metabolism, improving lipid profile, and lowering inflammatory cytokine levels in animal models and preliminary human trials. This review focuses on the potential role of blueberries as a functional food in the prevention and treatment of obesity and its comorbidities. Although the current evidence is promising, further randomized controlled studies in the longer term are needed to evaluate the role of blueberries and blueberry extracts to support human health. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the impact of air ventilation clothing (AVC) on the thermal comfort of workers involved in decreasing and intermittent activities in a hot-humid environment. Performance of the AVC with fan-OFF (CON) and fan-ON (AVC) are compared in a climate chamber that is maintained at 38 °C and 45% RH. It was found that the AVC could significantly (p < 0.05) improve the torso perceptual sensations in both the activity scenarios, but it could not significantly improve perceptual sensations for the whole body. For the majority of time during the trials, the mean torso, core, and mean body temperatures were significantly (p < 0.05) lowered with the use of AVC for both the activity scenarios. The highest drop in maximum local skin temperatures is found in the upper-arm (0.77 °C) and chest (0.61 °C) segments for decreasing and intermittent activity scenarios, respectively. It can be inferred from the present study that AVC is more beneficial for intermittent activity scenarios as compared to decreasing activity scenarios in a hot-humid environment in terms of limiting core and mean body temperatures. Sweat evaporation efficiency increased by 13.7% and 11.9% with the use of AVC for the decreasing and intermittent activity scenarios, respectively. Furthermore, performance of AVC is compared for different recovery period conditions during the intermittent activity scenario. In addition, the outcomes of this study expand the acceptable range of activity scenarios in which AVC can be utilized to minimize heat stress and increase the wearer's thermal comfort. • Performance of ventilation clothing is analyzed in hot-humid climate (38 °C, 45% RH). • Human trial study is done for intermittent and decreasing activity scenarios. • Torso perceptual sensations improved significantly in AVC case (p < 0.05). • AVC significantly reduced heat storage, mean torso and core temperatures (p < 0.05). • AVC improved sweat evaporation rate and efficiency in both activity scenarios. [ABSTRACT FROM AUTHOR]