Evidence is increasing that disturbances in the gut microbiome may play a significant role in the etiology of obesity and type 2 diabetes. The short chain fatty acid butyrate, a major end product of the bacterial fermentation of indigestible carbohydrates, is reputed to have anti-inflammatory properties and positive effects on body weight control and insulin sensitivity. However, whether butyrate has therapeutic potential for the treatment and prevention of obesity and obesity-related complications remains to be elucidated. Overall, animal studies strongly indicate that butyrate administered via various routes (e.g., orally) positively affects adipose tissue metabolism and functioning, energy and substrate metabolism, systemic and tissue-specific inflammation, and insulin sensitivity and body weight control. A limited number of human studies demonstrated interindividual differences in clinical effectiveness suggesting that outcomes may depend on the metabolic, microbial, and lifestyle-related characteristics of the target population. Hence, despite abundant evidence from animal data, support of human data is urgently required for the implementation of evidence-based oral and gut-derived butyrate interventions. To increase the efficacy of butyrate-focused interventions, future research should investigate which factors impact treatment outcomes including baseline gut microbial activity and functionality, thereby optimizing targeted-interventions and identifying individuals that merit most from such interventions.

The liver is an essential organ that helps the body with immunity, metabolism, and detoxification, among other functions. Worldwide, liver illnesses are a leading cause of mortality and disability. There are few effective treatment choices, but they frequently have unfavorable side effects. Investigating the potential of medicinal plants and their bioactive phytoconstituents in the prevention and treatment of liver disorders has gained more attention in recent years. An assessment of the hepatoprotective potential of medicinal plants and their bioactive secondary metabolites is the goal of this thorough review paper. To determine their hepatoprotective activity, these plants were tested against liver toxicity artificially induced in rats, mice and rabbits by chemical agents such as carbon tetrachloride (CCl4), paracetamol (PCM), thioacetamide (TAA), N-nitrosodiethylamine, d-galactosamine/lipopolysaccharide, antitubercular medicines (rifampin, isoniazid) and alcohol. To find pertinent research publications published between 1989 and 2022, a comprehensive search of electronic bibliographic databases (including Web of Science, SpringerLink, ScienceDirect, Google Scholar, PubMed, Scopus, and others) was carried out. The investigation comprised 203 plant species from 81 families in total. A thorough discussion was mentioned regarding the hepatoprotective qualities of plants belonging to several families, such as Fabaceae, Asteraceae, Lamiaceae, and Euphorbiaceae. The plant groups Asteraceae and Fabaceae were the most frequently shown to have hepatoprotective properties. The phytochemical constituents namely flavonoids, phenolic compounds, and alkaloids exhibited the highest frequency of hepatoprotective action. Also, some possible mechanism of action of some active constituents from medicinal plants was discussed in brief which were found in some studies. In summary, the information on medicinal plants and their potentially hepatoprotective bioactive phytoconstituents has been consolidated in this review which emphasizes the importance of further research to explore the efficacy and safety of these natural remedies for various liver ailments.

Resting-state functional connectivity (rsFC) is an emerging means of understanding the neurobiology of combat-related post-traumatic stress disorder (PTSD). However, most rsFC studies to date have limited focus to cognitively related intrinsic connectivity networks (ICNs), have not applied data-driven methodologies or have disregarded the effect of combat exposure. In this study, we predicted that group independent component analysis (GICA) would reveal group-wise differences in rsFC across 50 active duty service members with PTSD, 28 combat-exposed controls (CEC), and 25 civilian controls without trauma exposure (CC). Intranetwork connectivity differences were identified across 11 ICNs, yet combat-exposed groups were indistinguishable in PTSD vs CEC contrasts. Both PTSD and CEC demonstrated anatomically diffuse differences in the Auditory Vigilance and Sensorimotor networks compared to CC. However, intranetwork connectivity in a subset of three regions was associated with PTSD symptom severity among executive (left insula; ventral anterior cingulate) and right Fronto-Parietal (perigenual cingulate) networks. Furthermore, we found that increased temporal synchronization among visuospatial and sensorimotor networks was associated with worse avoidance symptoms in PTSD. Longitudinal neuroimaging studies in combat-exposed cohorts can further parse PTSD-related, combat stress-related or adaptive rsFC changes ensuing from combat.

Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes.

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to measure brain chemistry in vivo and has been used to study the healthy brain as well as neuropathology in numerous neurological disorders. The number of multi-site studies using MRS are increasing; however, non-biological variability introduced during data collection across multiple sites, such as differences in scanner vendors and site-specific acquisition implementations for MRS, can obscure detection of biological effects of interest. ComBat is a data harmonization technique that can remove non-biological sources of variance in multisite studies. It has been validated for use with structural and functional MRI metrics but not for MRS measured metabolites. This study investigated the validity of using ComBat to harmonize MRS metabolites for vendor and site differences. Analyses were performed using data acquired across 20 sites and included edited MRS for GABA+ (N = 218) and macromolecule-suppressed GABA data (N = 209), as well as standard PRESS data to quantify NAA, creatine, choline, and glutamate (N = 190). ComBat harmonization successfully mitigated vendor and site differences for all metabolites of interest. Moreover, significant associations were detected between sex and choline levels and between age and glutamate and GABA+ levels that were not detectable prior to harmonization, confirming the importance of removing site and vendor effects in multi-site data. In conclusion, ComBat harmonization can be successfully applied to MRS data in multi-site MRS studies.

Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amygdala is a key brain region involved in threat detection and fear regulation, and previous animal studies have suggested that stress sensitizes amygdala responsivity and reduces its regulation by the prefrontal cortex. In this study, we used a prospective design to investigate the consequences of severe stress in soldiers before and after deployment to a combat zone. We found that combat stress increased amygdala and insula reactivity to biologically salient stimuli across the group of combat-exposed individuals. In contrast, its influence on amygdala coupling with the insula and dorsal anterior cingulate cortex was dependent on perceived threat, rather than actual exposure, suggesting that threat appraisal affects interoceptive awareness and amygdala regulation. Our results demonstrate that combat stress has sustained consequences on neural responsivity, and suggest a key role for the appraisal of threat on an amygdala-centered neural network in the aftermath of severe stress.

Melatonin, also known as N-acetyl-5-methoxytryptamine, is a ubiquitously acting molecule that is produced by the pineal gland and other organs of animals, including humans. As melatonin and its metabolites are potent antioxidants and free radical scavengers, they are protective against a variety of disorders. Moreover, multiple molecular targets of melatonin have been identified, and its actions are both receptor-mediated and receptor-independent. Recent studies have shown that melatonin may be useful in fighting against sepsis and septic injury due to its antioxidative and anti-inflammatory actions; the results generally indicate a promising therapeutic application for melatonin in the treatment of sepsis. To provide a comprehensive understanding regarding the protective effects of melatonin against septic injury, in the present review we have evaluated the published literature in which melatonin has been used to treat experimental and clinical sepsis. Firstly, we present the evidence from studies that have used melatonin to resist bacterial pathogens. Secondly, we illustrate the protective effect of melatonin against septic injury and discuss the possible mechanisms. Finally, the potential directions for future melatonin research against sepsis are summarized.

Posttraumatic stress disorder (PTSD) is complex neuropsychiatric disorder triggered by a traumatic event and characterized by the symptoms that represent large burden to patients, as well as to society. Lipidomic approach can be applied as a useful tool for discovery of novel diagnostic, prognostic and therapeutic lipid biomarkers of various disorders, whose etiology is complex and still unknown, including PTSD. Since changes in the levels of lipid metabolites might indicate impairments in various metabolic pathways and cellular processes, the aim of this lipidomic study was to determine altered levels of lipid compounds in PTSD. The study enrolled 235 male patients with combat PTSD and 241 healthy male control subjects. Targeted lipidomic analysis of plasma samples was conducted using reverse-phase liquid chromatography coupled with mass spectrometry. Lipids that have been analyzed belong to the group of ceramides, cholesterol esters, diacylglycerols, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins and triglycerides. The levels of fifteen lipid compounds were found to be significantly different between PTSD patients and healthy control subjects, including four phosphatidylcholines, two phosphatidylethanolamines, five sphingomyelins, two cholesterol esters and two ceramides. The lipid metabolites whose levels significantly differed between patients with PTSD and control subjects are associated with various biological processes, including impairments of membrane integrity and function, mitochondrial dysfunction, inflammation and oxidative stress. As these processes might be associated with development and progression of PTSD, altered lipid compounds represent potential biomarkers that could facilitate the diagnosis of PTSD, prediction of the disease, as well as identification of novel treatment approaches in PTSD.

Ependymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid (RNA). These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles. However, the interaction between viruses and host organelles may be disrupted by nanomaterials, such as gold nanoparticles (AuNPs) with unique physical and chemical properties. In this study, we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells, and their effects on two representative enveloped RNA viruses: lentivirus and human coronavirus OC43 (HCoV- OC43) antiviral potential. By comparing the subcellular effects of AuNPs with different surface charge properties, we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs, mainly manifested in lysosomes and Cytoskeletal disorders. The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43. The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects. In conclusion, our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems, while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.

Drug counterfeiting has serious public health and safety implications. The objective of this study was to systematically review the evidence on the effectiveness of interventions to combat or prevent drug counterfeiting.

While aggregation of neuroimaging datasets from multiple sites and scanners can yield increased statistical power, it also presents challenges due to systematic scanner effects. This unwanted technical variability can introduce noise and bias into estimation of biological variability of interest. We propose a method for harmonizing longitudinal multi-scanner imaging data based on ComBat, a method originally developed for genomics and later adapted to cross-sectional neuroimaging data. Using longitudinal cortical thickness measurements from 663 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, we demonstrate the presence of additive and multiplicative scanner effects in various brain regions. We compare estimates of the association between diagnosis and change in cortical thickness over time using three versions of the ADNI data: unharmonized data, data harmonized using cross-sectional ComBat, and data harmonized using longitudinal ComBat. In simulation studies, we show that longitudinal ComBat is more powerful for detecting longitudinal change than cross-sectional ComBat and controls the type I error rate better than unharmonized data with scanner included as a covariate. The proposed method would be useful for other types of longitudinal data requiring harmonization, such as genomic data, or neuroimaging studies of neurodevelopment, psychiatric disorders, or other neurological diseases.

The current COVID-19 pandemic remains severe. There is no doubt that the COVID-19 pandemic is affecting every aspect of our lives. Currently, the spread of inaccurate information or fake news on the internet to the public is causing the community to panic. Thus, this study aims to obtain available information on food and nutrition related to the prevention and treatment of COVID-19 from various sources. A scoping review framework was used to chart the evidence on nutritional recommendations to prevent COVID-19 based on the preferred method in reporting systematic review and meta-analysis extension for scoping reviews (PRISMA-ScR). The articles were categorised into three main groups: i) general dietary recommendations; ii) supplementation with specific micronutrients and iii) their mixtures and supplementation with traditional herbs and miscellaneous foods. A total of 60 articles met the inclusion criteria and were used in the review. This scoping review demonstrates that there is no miracle cure, food or supplement that can cure or prevent COVID-19. Currently, there is no confirmed treatment or vaccine for the disease. Practicing healthy eating habits is the best nutritional recommendation during the pandemic. Hence, this review hopefully will provide evidence-based nutrition recommendations that are available for current COVID-19 treatment. We hope that the authorities can inform the public and media to stop the spread of nutrition pseudoscience in the wake of the COVID-19 pandemic.

Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous presence of adenosine receptors in different organs and the short half-life of adenosine in circulation. Towards this, we have developed a bone-targeting nanocarrier and determined its potential for systemic administration of adenosine. The nanocarrier, synthesized via emulsion suspension photopolymerization, is comprised of hyaluronic acid (HA) copolymerized with phenylboronic acid (PBA), a moiety that can form reversible bonds with adenosine. The bone binding affinity of the nanocarrier was achieved by alendronate (Aln) conjugation. Nanocarriers functionalized with the alendronate (Aln-NC) showed a 45% higher accumulation in the mice vertebrae in vivo compared to those lacking alendronate molecules (NCs). Systemic administration of adenosine via bone-targeting nanocarriers (Aln-NC) attenuated bone loss in ovariectomized (OVX) mice. Furthermore, bone tissue of mice treated with adenosine-loaded Aln-NC displayed trabecular bone characteristics comparable to healthy controls as shown by microcomputed tomography, histochemical staining, bone labeling, and mechanical strength. Overall, our results demonstrate the use of a bone-targeting nanocarrier towards systemic administration of adenosine and its application in treating bone degenerative diseases such as osteoporosis.

The aim of this systematic review was to analyse the studies centered on the effects of Olympic combat sports (OCS [i.e., boxing, fencing, judo, karate, taekwondo, wrestling]) on older adults' physical-functional, physiological, and psychoemotional health status. The review comprised randomised-controlled trials with OCS interventions, including older adults (≥60 years), and measures of physical-functional, physiological, and/or psychoemotional health. The studies were searched through SCOPUS, PubMed/MEDLINE, Web of Science, PsycINFO, and EBSCO databases until 5 January 2021. The PRISMA-P and TESTEX scales were used to assess the quality of the selected studies. The protocol was registered in PROSPERO (code: CRD42020204034). Twelve OCS intervention studies were found (scored ≥ 60% for methodological quality), comprising 392 females and 343 males (mean age: 69.6 years), participating in boxing, judo, karate, and taekwondo. The qualitative analysis revealed that compared to controls, OCS training improved muscle strength, cardiorespiratory capacity, agility, balance, movement, attention, memory, mental health, anxiety, and stress tolerance. Meta-analysis was available only for the chair stand test, and an improvement was noted after OCS training compared to control. In conclusion, OCS interventions improves older adults' physical-functional, physiological, and psychoemotional health. Our systematic review confirms that OCS training has high adherence (greater than 80%) in older adults.

Antibiotic resistance has become a growing global problem where overprescription is a contributing factor for its development. In the endodontics field, complementary treatments, such as antimicrobial photodynamic therapy (aPDT), have been described to eliminate residual bacteria from the root canal space and reduce complications. The aim of this review is to describe the literature evidence up to now regarding the advantages, efficiency, and clinical outcomes of this therapy in endodontics as a possible tool to combat antibiotic resistance.

Cardiovascular disease (CVD) is a leading cause of death among military veterans with several reports suggesting a link between combat and related traumatic injury (TI) to an increased CVD risk. The aim of this paper is to conduct a widespread systematic review and meta-analysis of the relationship between military combat ± TI to CVD and its associated risk factors.

Increasing epidemic proportions of overweight children in the United States presents formidable challenges for education and healthcare. Given the popularity and pervasiveness of video gaming culture in North American children, the perfect opportunity arises to investigate the potential of video games to promote healthful behaviour. Our objective was to systematically review the literature for possible benefits of active and educational video games targeting diet and physical activity in children. A review of English-language journal articles from 1998 to 2011 using EMBASE and PubMed was conducted. Thirty-four studies concerned with children, video games, physical, and/or nutritional outcomes were included. Results of these studies that showed some benefit (increased physical activity and nutritional knowledge as a result of gaming) demonstrate the possibility of video games to combat childhood obesity-looking beyond the stigma attached to gaming.

This review aimed to identify the effects of strength training programs on the physical fitness of Olympic combat sports (OCS) athletes. The systematic review included peer-reviewed articles that incorporated interventions that included pre- and post-intervention physical fitness assessment. The search was performed in the SCOPUS, PubMed, and Web of Science databases between April and September 2022. PRISMA and the TESTEX checklist were used to select and assess the methodological quality of the studies. Twenty studies with 504 participants (428 males and 76 females) were included. Significant improvements were found in athletes' maximal dynamic and isometric strength, muscle power, flexibility, and balance. In addition, improvements in favor of the training groups in specific actions of judo, karate, fencing, and boxing were observed. In conclusion, interventions aimed at the development of muscle strength in OCS, specifically in judo, boxing, karate, wrestling, and fencing, proved to be beneficial at a physical fitness level, resulting in significant increases in favor of the training groups with OCS, which could be used by trainers and coaches to improve the physical performance of athletes.