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BioRxiv : the Preprint Server For... Jun 2024Monogenic skin disorders such as ichthyosis introduce multiple sources of disturbance to the skin, including the direct biochemical consequences of the genotype, the...
Monogenic skin disorders such as ichthyosis introduce multiple sources of disturbance to the skin, including the direct biochemical consequences of the genotype, the phenotypic changes in skin physiology, and an altered skin microbiome. The association between changes in the skin microbiome and the disease's genotypic and phenotypic effects are of both ecological and clinical interest but are historically obscured by 1) the limited resolution of metagenomic profiles, and 2) additional sources of variation such as age and topical/oral treatments. Here we characterize the skin microbiome from seven ichthyosis genotypes, at species, strain, and metabolic pathway levels. Critically, we assess the association between these microbiome features and the ichthyosis genotype and phenotype while adjusting for contextual host covariables. We show that the ichthyosis genotype, especially that caused by mutations in TGM1, and the ichthyosis phenotype, particularly transepidermal water loss (TEWL), and personal covariables, such as topical emollients and oral retinoids, collectively, and sometimes antagonistically, influence the species community, strain population, and metabolic potential of the skin microbiome.
PubMed: 38948872
DOI: 10.1101/2024.06.17.599414 -
BioRxiv : the Preprint Server For... Jun 2024Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially...
Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially when it is unwanted. We used a novel social touch assay and Neuropixels probes to compare neural responses to social vs. non-social interactions in three relevant brain regions: vibrissal somatosensory cortex, tail of striatum, and basolateral amygdala. We find that wild type (WT) mice showed aversion to repeated presentations of an inanimate object but not of another mouse. Cortical neurons cared most about touch context (social vs. object) and showed a preference for social interactions, while striatal neurons changed their preference depending on whether mice could choose or not to interact. Amygdalar and striatal neurons were preferentially modulated by forced object touch, which was the most aversive. In contrast, the knockout (KO) model of autism found social and non-social interactions equally aversive and displayed more aversive facial expressions to social touch when it invaded their personal space. Importantly, when KO mice could choose to interact, neurons in all three regions did not discriminate social valence. Thus, a failure to differentially encode social from non-social stimuli at the circuit level may underlie social avoidance in autism.
PubMed: 38948773
DOI: 10.1101/2024.06.19.599778 -
Journal of Family Medicine and Primary... May 2024It has been well reported that medical students do not follow healthy diets overall. Effectively guiding patients to change their health behavior is a crucial skill for...
INTRODUCTION
It has been well reported that medical students do not follow healthy diets overall. Effectively guiding patients to change their health behavior is a crucial skill for primary care providers and family physicians. Our objective was to investigate medical students' dietary decision-making, including the motivations and barriers that influence their dietary choices.
METHODS
A self-administered online questionnaire was conducted among preclinical students at one allopathic medical school in the United States. The survey was comprised of questions about students' dietary goals, habits, and the barriers they face in reaching their nutritional ideals. Trends in the percentage of students who selected each survey answer choice were interpreted.
RESULTS
Of the 363 preclinical students provided with the optional survey, 71 (19.6%) chose to participate. The participants' dietary decisions were predominately driven by convenience. Most students wanted to eat nutritiously to support their well-being but had been eating less healthily since starting medical school due to financial limitations and limited time. Approximately half (46.5%, 33/71) of the participants stated that they would buy the in-house food provided at the medical school campus more often if it better matched their dietary goals, but 36.6% (26/71) would only do so if the new foods were affordable compared to competitor's prices.
CONCLUSION
There is an opportunity to help medical students meet their dietary goals, which are negatively impacted by personal and structural academic barriers. Further research is needed on the obstacles that institutions face in offering healthy, affordable options to medical students.
PubMed: 38948602
DOI: 10.4103/jfmpc.jfmpc_1016_23 -
Crohn's & Colitis 360 Apr 2024In 2022, the Food and Drug Administration (FDA) updated its draft guidance for drug development in ulcerative colitis, replacing the version from 2016. Several changes...
BACKGROUND
In 2022, the Food and Drug Administration (FDA) updated its draft guidance for drug development in ulcerative colitis, replacing the version from 2016. Several changes from the 2016 version merit further discussion as they impact clinical trial design and the interpretation of trial results.
METHODS
We compared both documents and critically appraised the changes and implications for future clinical trials.
RESULTS
The 2022 guidance recommends full colonoscopy, rather than flexible sigmoidoscopy, to document disease activity in all involved segments of the colon. The concordance between the findings of the 2 procedures is very high and there is little evidence to support colonoscopy over sigmoidoscopy. The use of colonoscopy, rather than sigmoidoscopy, is also associated with a higher burden to trial participants who must undergo full bowel preparation, cost, and a potential for more adverse events. The definition of the Mayo endoscopic score of 0 was changed from the original publication to "normal appearance of mucosa," which suggests that endoscopic signs of prior disease, such as pseudopolyps and scarring, are incompatible with a score 0, even though they are not associated with active disease. The term "mucosal healing" has been abolished and histologic outcomes defined as exploratory. A welcome change is that shorter washout periods than 5 half-lives will be considered to reduce patient exposure to corticosteroids as bridging therapy.
CONCLUSIONS
The 2022 FDA draft guidance includes changes which for the most part are not informed by empirical evidence, which may ultimately complicate interpretation of future trials and preclude comparisons with past trials.
PubMed: 38948490
DOI: 10.1093/crocol/otae038 -
Frontiers in Pharmacology 2024Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid...
Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD. A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors. After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = -2.58 [-3.29, -1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = -3.47 [-4.97, -1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress. This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.
PubMed: 38948464
DOI: 10.3389/fphar.2024.1411566 -
Drug and Alcohol Dependence Reports Jun 2024In the past few years, technological advancements enabled the development of novel electronic nicotine delivery systems (ENDS). Several empirical measures such as...
In the past few years, technological advancements enabled the development of novel electronic nicotine delivery systems (ENDS). Several empirical measures such as "nicotine flux" are being proposed to evaluate the abuse liability potential of these products. We explored the applicability of nicotine flux for clinical nicotine pharmacokinetics (PK) and 52-week quit success from cigarettes for a wide range of existing nicotine delivery systems. We found that the differences in nicotine flux for various nicotine delivery systems are not related to changes in PK, as nicotine flux does not capture key physiological properties such as nicotine absorption rate. Further, the 52-week quit success and abuse liability potential of nicotine nasal sprays (high nicotine flux product), and nicotine inhalers (nicotine flux similar to ENDS) are low, suggesting that nicotine flux is a poor metric for the assessment of nicotine delivery systems. PK indices are more dependable for characterizing nicotine delivery systems, and a nicotine plasma > 1 could improve 52-week quit success from cigarettes. However, a single metric may be inadequate to fully assess the abuse liability potential of nicotine delivery systems and needs to be further studied. A combination of and approaches could potentially address the factors influencing the inhaled aerosol dosimetry and resulting PK of nicotine to provide early insights for ENDS assessments. Further research is required to understand nicotine dosimetry and PK for product use, and abuse liability indicators of nicotine delivery systems. This commentary is intended to (1) highlight the need to think beyond a single empirical metric such as nicotine flux, (2) suggest potential PK-based metrics, (3) suggest the use of and tools to obtain early insights into inhaled aerosol dosimetry for ENDS, and (4) emphasize the importance of considering comprehensive clinical pharmacology outcomes to evaluate nicotine delivery systems.
PubMed: 38948427
DOI: 10.1016/j.dadr.2024.100245 -
Contemporary Clinical Trials... Jun 2024Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without...
INTRODUCTION
Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS).
METHODS AND ANALYSIS
In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks.
ETHICS AND DISSEMINATION
This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]).
CLINICAL TRIAL REGISTRATION
Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.
PubMed: 38948333
DOI: 10.1016/j.conctc.2024.101317 -
Journal of Clinical & Translational... Jun 20241.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist...
BACKGROUND
1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity.
OBJECTIVES
To determine the effects of 12 months of testosterone on cardiometabolic health among transgender youth, including insulin sensitivity, body composition, and bone mineral density and whether changes in outcomes differ based on prior GnRHa treatment.
METHODS
Participants (n = 19, baseline age 15.0 ± 1.0 years) were examined prior to and 12 months after testosterone therapy in a longitudinal observational study. Fasted morning blood draw, a 2-hour 75-gram oral glucose tolerance test, body composition and bone mineral density (dual-energy X-ray absorptiometry) were assessed at baseline and 12 months. Insulin sensitivity was estimated by HOMA-IR and Matsuda index. Changes were compared with mixed linear regression models evaluating time (baseline, 12 months), group (GnRHa treatment yes/no), and their interaction.
RESULTS
In the entire cohort, fasted insulin decreased (median [25,75 %ile]: -3 [-5, 0] mIU/L, p = 0.044) and 2-hour glucose increased (mean ± standard deviation): +18.5 ± 28.9 mg/dL, p = 0.013 from baseline after 12 months of testosterone therapy. There were no significant changes in HOMA-IR (p = 0.062) or Matsuda index (p = 0.096), nor by GnRHa status. Absolute (+6.2 [4.7, 7.5] kg, p = 0.016) and percent fat-free mass increased (+7.3 [5.4, 9.1] %, p = 0.003) and percent fat mass declined (-7.4 [-9.3, 5.3]%, p = 0.005) for the entire cohort. There were time*group interactions for absolute (p = 0.0007) and percent fat-free mass (p = 0.033). There were time*group interactions for bone mineral content (p = 0.006).
CONCLUSIONS
Twelve months of testosterone in transgender adolescents resulted in changes in body composition and bone mineral density, with baseline differences between the +/-GnRHa group and convergence after 12 months. There were no changes in insulin sensitivity over time or between groups.
PubMed: 38948245
DOI: 10.1016/j.jcte.2024.100356 -
Journal of Clinical & Translational... Jun 2024Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in...
BACKGROUND AND AIM
Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors.
METHODS
Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors.
RESULTS
On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters.
CONCLUSION
Probiotic supplementation with did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.
PubMed: 38948244
DOI: 10.1016/j.jcte.2024.100357 -
The effects of occupational disruption during COVID-19 lockdowns on health: a cross-sectional study.PeerJ 2024The disruption in daily activity performance during COVID-19 lockdowns is widely understood to have impacted health, but a better understanding of how restricted...
The disruption in daily activity performance during COVID-19 lockdowns is widely understood to have impacted health, but a better understanding of how restricted performance of specific activities are associated with health is needed. This cross-sectional study answers the following question: How were changes in the performance of 16 daily activities associated with health during COVID-19 lockdowns? A total of 116 participants completed an online survey rating their health before and during COVID-19 lockdowns and comparing their recollection of the performance of 16 activities before COVID-19 with their performance during lockdowns. Multiple stepwise linear regression analysis was used to estimate the relationship between self-reported changes in activities during lockdowns and concurrent (during-lockdown) health status, while controlling for pre-COVID-19 health status. Only changes in activities that were uniquely and significantly associated with lockdown health status were retained in the final model. Health before COVID-19 accounted for 3.7% ( = 0.039) of the variance in health during COVID-19 lockdowns. After controlling for health before COVID-19, five types of activity were significantly and uniquely predictive of health during lockdowns, together accounting for 48.3% of the variance. These activities and the variances they accounted for were rest and sleep (29.5%, < 0.001), play and recreational activities (8%, < 0.001), work (4.8%, = 0.002), personal hygiene (3.2%, = 0.01), and healthy eating (2.8%, = 0.013). The study suggests that these five types of activity should be prioritized in policy or interventions when participation in activity is constrained by lockdowns or comparable factors.
PubMed: 38948220
DOI: 10.7717/peerj.17594