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Mastication plays an important role in effective food digestion and nutrient absorption. Therefore, regulating masticatory force in people with declining mastication function is significant for maintaining health and quality of life. In this study, we tested the effect of tactile augmentation on mastication force. To augment tactile feedback during mastication, we applied closed-loop electrical stimulation onto the mandibular vestibule using an intraoral tooth-borne electronic system. We hypothesized that closed-loop electrical stimulation, timed with mastication and applied to the nerves delivering tactile feedback to the brain, would evoke an increase in masticatory force. Experiments were completed using the intraoral system with six healthy human subjects who masticated soft and hard foods with and without stimulation during the experiment. Their mastication forces were recorded ten times per condition. The recorded mastication force profile showed that mastication force was higher with the harder food. Also, mastication force increased when electrical stimulation was applied, compared to the non-stimulated condition. These results support the hypothesis that tactile augmentation by intraoral closed-loop electrical stimulation will increase masticatory force. Other mastication parameters including period, spike width, and duty cycle are also changed by electrical stimulation. Further, stimulation left a strong aftereffect on these mastication parameters.

Abstract Background There is evidence that exercise may reduce the risk of gestational diabetes mellitus (GDM) and improve other obstetric outcomes in overweight or obese pregnant women. However, the available evidence is of low quality and inconclusive. The purpose of this study is to assess the effects of exercise, compared with usual care, in reducing GDM and other obstetric risks, in overweight and obese pregnant women. Methods We searched MEDLINE, Embase, and the Cochrane Library from their inception dates up to August 2022. Randomised studies comparing physical exercise versus routine obstetric care in pregnant women with overweight or obesity (BMI ≥ 25.0). Each abstract and full-text article was independently reviewed by the same two authors. The primary outcome was the incidence of GDM, and the secondary outcomes were excessive weight gain, preterm delivery, and foetal macrosomia. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Main Results. Seven studies covering 1162 patients were identified. Exercise did not reduce the risk of GDM: RR, 0.82 [95% CI, (0.58–1.17)] but subgroup analysis shows a significant benefit among patients adhering to the programs: RR, 0.56 [95% CI, (0.40–0.78)] and no effect among non-adherents: RR, 1.11 [95% CI, (0.82–1.50)]. We did not find a significant effect on excessive weight gain: RR, 0.92 [95% CI, (0.76–1.11)] but there was a reduction in the risk of foetal macrosomia: RR, 0.5 [95% CI, (0.32–0.79)]. Exercise has not been associated with an increased risk of preterm birth: RR, 0.79 [95% CI, (0.44–1.39)]. Conclusions The present study does not allow us to conclude that structured exercise programs for pregnant women with overweight or obesity leads to a reduction in the risk of gestational diabetes. When exercise program adherence is high, a significant reduction of GDM is observed. These findings will need to be confirmed with large primary trials. A reduction in the incidence of foetal macrosomia has also been observed. Trial registration This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; identifier: CRD42023399004).

The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response.CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts.Our GWAS identified two genome-wide significant (P

Rhizopus rot is considered one of the most common diseases influencing global production and yield of horticulture commodities. However, the factors contributing to this pattern of prevalence are uncertain. Here, we focused on R. microsporus, which is known to rely on its endosymbiotic bacterium, Mycetohabitans, to produce toxins that interfere with plant development and inhibit the growth of other fungi. We assessed the impact of the symbiotic R. microsporus harboring its endosymbiont as well as the fungus cured of it on: (1) the magnitude of spoilage in tomato fruits, as evaluated by Koch's postulate for pathogenicity, (2) the shifts in native communities of endophytic fungi inhabiting these fruits, as examined by ITS rRNA gene metabarcoding and (3) secondary metabolites generated by these communities, as analyzed using multi-analyte LC-MS/MS. The pathogenicity test showed that the symbiotic endobacterium-containing R. microsporus W2-50 was able to cause tomato fruit spoilage. This was accompanied by decreased relative abundance of Alternaria spp. and an increase in the relative abundance of Penicillium spp. that may have facilitated the observed spoilage. In conclusion, symbiotic W2-50 appeared to facilitate fruit spoilage, possibly through successful colonization or toxin production by its endosymbiont.

Autism spectrum disorders (ASD) are complex human neurodiversities increasing in prevalence within the human population. In search of therapeutics to improve quality-of-life for ASD patients, the gut microbiome (GM) has become a promising target as a growing body of work supports roles for the complex community of microorganisms in influencing host behavior via the gut-brain-axis. However, whether naturally-occurring microbial diversity within the host GM affects these behaviors is often overlooked. Here, we applied a model of population-level differences in the GM to a classic ASD model – the BTBR T+ Itpr3tf/J mouse – to assess how complex GMs affect host behavior. Leveraging the naturally occurring differences between supplier-origin GMs, our data demonstrate that differing, complex GMs selectively effect host ASD-related behavior – especially neonatal ultrasonic communication – and reveal a male-specific effect on behavior not typically observed in this strain. We then identified that the body weight of BTBR mice is influenced by the postnatal GM which was potentially mediated by microbiome-dependent effects on energy harvest in the gut. These data provide insight into how variability within the GM affects host behavior and growth, thereby emphasizing the need to incorporate microbial diversity within the host GM as an experimental factor in biomedical research.

Crimean-Congo haemorrhagic fever virus (CCHFV) causes human disease ranging from subclinical to a fatal haemorrhagic syndrome. Determinants of CCHF pathogenesis are largely unknown and animal models that recapitulate human disease are limited. A recently described mouse model uses a monoclonal antibody (mAb 5A3) targeting the interferon (IFN) alpha/beta receptor to suppress type I IFN responses, making animals transiently susceptible to infection. To advance utility of this model, we investigated effects of challenge route, timing of 5A3 delivery, mouse sex and age, and virus strain on clinical course and outcome. C57BL/6J mice received mAb 5A3 −1, 0, or −1/+1 days post-infection (dpi). Subsets were challenged with CCHFV strain Turkey04 or IbAr10200 subcutaneously or intraperitoneally, and serially euthanized 3- and 7-dpi, when meeting euthanasia criteria or at study completion (14 dpi). CCHFV-IbAr10200-infected mice almost uniformly succumbed to infection, whereas CCHFV-Turkey04-infected mice transiently lost weight but survived. These results were consistent regardless of mAb timing or route of challenge. Viral replication and dissemination were comparable between the two strains at 3 dpi. However, in the plasma and livers of non-survivors, expression of proinflammatory cytokines/chemokines that correspond with macrophage activation and recruitment were significantly elevated. Lethal disease was also associated with elevated levels of macrophage activation marker CD163 in plasma. Further, mouse macrophages were more permissive to IbAr1200 infection in vitro, suggesting tropism for these cells may influence pathogenesis. Our data suggest that early inflammation may be a critical determinant of CCHF outcome and therapeutics to control inflammation may be worthwhile targets for future investigation.

Abstract Objective To report initial results from the Amyotrophic Lateral Sclerosis (ALS) Identified genetic testing (GT) program on characteristics of individuals tested and frequency of reported disease‐causing variants. Methods ALS Identified used the Invitae Amyotrophic Lateral Sclerosis panel (Invitae, San Francisco, CA, USA) to assay 22 ALS‐associated genes. Sponsored by Biogen (Cambridge, MA, USA), the program was launched in June 2021 and was available at no charge to individuals ≥18 years in the United States and Puerto Rico with an ALS diagnosis or a known family history of ALS. Deidentified data were available to Biogen. Results As of 26 October 2023, 998 healthcare professionals ordered the panel at 681 unique care sites. Of 8054 individuals examined, 7483 (92.9%) were reported to have a clinical diagnosis of ALS, while 571 (7.1%) were asymptomatic relatives. Of the individuals with a clinical ALS diagnosis, 57.7% were male (n = 4319) and 42.3% female (n = 3164). Mean (SD) age at diagnosis is 62 (13) years. Out of the 7483 clinically diagnosed individuals, 1810 (24.2%) showed genetic variations in ALS‐associated genes. Among these, 865 individuals (47.8%) carried pathogenic variants, and 44 (2.4%) had likely pathogenic variants, totaling 12.1% of the clinically diagnosed population. Interpretation Since 2021 there has been robust uptake and sustained use of the ALS Identified program, one of the largest samples of people with ALS to date across the United States, demonstrating the interest and need for genetic ALS testing.

Abstract INTRODUCTION Adverse psychosocial exposure is associated with increased pro‐inflammatory gene expression and reduced type‐1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well‐studied in cognitive impairment but may contribute to late‐life cognitive decline. METHODS We examined perceived stress, loneliness, well‐being, and the impact of coronavirus disease 2019 (COVID‐19) and the relationship to the expression of genes associated with the CTRA. Mixed‐effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. RESULTS Eudaimonic well‐being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self‐reported coping strategies differed by cognitive status and variably impacted CTRA gene expression. DISCUSSION EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. Highlights Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well‐being. Eudaimonic well‐being was important in both participants with normal cognition and those with mild cognitive impairment. Coping strategies and impact on CTRA gene expression differed by cognitive status. Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.

IntroductionTongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons.MethodsRats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles.ResultsResults showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise.ConclusionThese findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.

BackgroundCoronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multidimensional individual characteristics. We sought to investigate the heterogeneity in the association between positive CAC and incident CVD.MethodsThis cohort study included adults from MESA (Multi-Ethnic Study of Atherosclerosis) ages ≥45 years and free of cardiovascular disease. After propensity score matching in a 1:1 ratio, we applied a machine learning causal forest model to (1) evaluate the heterogeneity in the association between positive CAC and incident CVD, and (2) predict the increase in CVD risk at 10-years when CAC>0 (versus CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC>0 to the absolute 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 American College of Cardiology/American Heart Association pooled cohort equations.ResultsAcross 3328 adults in our propensity score-matched analysis, our causal forest model showed the heterogeneity in the association between CAC>0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC>0 with higher 10-year ASCVD risk. Almost all individuals (2293 of 2428 [94.4%]) with borderline risk of ASCVD or higher showed ≥2.5% increase in CVD risk when CAC>0. Even among 900 adults with low ASCVD risk, 689 (69.2%) showed ≥2.5% increase in CVD risk when CAC>0; these individuals were more likely to be male, Hispanic, and have unfavorable CVD risk factors than others.ConclusionsThe expected increases in CVD risk when CAC>0 were heterogeneous across individuals. Moreover, nearly 70% of people with low ASCVD risk showed a large increase in CVD risk when CAC>0, highlighting the need for CAC screening among such low-risk individuals. Future studies are needed to assess whether targeting individuals for CAC measurements based on not only the absolute ASCVD risk but also the expected increase in CVD risk when CAC>0 improves cardiovascular outcomes.

The first genome sequenced of a eukaryotic organism was for Saccharomyces cerevisiae, as reported in 1996, but it was more than 10 years before any of the zygomycete fungi, which are the early-diverging terrestrial fungi currently placed in the phyla Mucoromycota and Zoopagomycota, were sequenced. The genome for Rhizopus delemar was completed in 2008; currently, more than 1000 zygomycete genomes have been sequenced. Genomic data from these early-diverging terrestrial fungi revealed deep phylogenetic separation of the two major clades-primarily plant-associated saprotrophic and mycorrhizal Mucoromycota versus the primarily mycoparasitic or animal-associated parasites and commensals in the Zoopagomycota. Genomic studies provide many valuable insights into how these fungi evolved in response to the challenges of living on land, including adaptations to sensing light and gravity, development of hyphal growth, and co-existence with the first terrestrial plants. Genome sequence data have facilitated studies of genome architecture, including a history of genome duplications and horizontal gene transfer events, distribution and organization of mating type loci, rDNA genes and transposable elements, methylation processes, and genes useful for various industrial applications. Pathogenicity genes and specialized secondary metabolites have also been detected in soil saprobes and pathogenic fungi. Novel endosymbiotic bacteria and viruses have been discovered during several zygomycete genome projects. Overall, genomic information has helped to resolve a plethora of research questions, from the placement of zygomycetes on the evolutionary tree of life and in natural ecosystems, to the applied biotechnological and medical questions.

Abstract Background Aerophagia (ingestion of air), is a functional aerodigestive disorder in people. Criteria for diagnosis of aerophagia in dogs are >1/3 of bolus volume containing air or ingested air resulting in gastric distention (>1/3 of end gastric volume). Aerophagia is highlighted during eating and drinking. Videofluoroscopic swallow studies (VFSS) document aerophagia in dogs, but the incidence, clinical signs (CS), and associated disorders are unknown. Objectives Identify the incidence of aerophagia, compare CS between dogs with and without aerophagia, and identify associated and predisposing disorders using VFSS. Animals A total of 120 client‐owned dogs. Methods Sequential VFSS and associated medical records from dogs presenting to veterinary teaching hospitals at Auburn University and the University of Missouri were retrospectively reviewed. Statistical comparisons were made using Mann‐Whitney and chi‐squared tests, odds ratios (OR), and multiple logistic regression (P

ImportanceInterventions directly targeting social factors, such as education, may have the potential to greatly improve health.ObjectiveTo examine the association of attending a high-performing public charter high school with rates of substance use disorder and physical and mental health.Design, setting, and participantsThis cohort study used the random school admissions lottery system of high-performing public charter high schools in low-income neighborhoods of Los Angeles, California, to examine the health outcomes of students who applied to at least 1 of 5 of these high schools. Participants attended 147 different high schools and were randomly selected from those who won the admissions lottery (intervention group) and those who were placed on a waiting list (control group). Participants were surveyed at the end of grade 8 through transition into grade 9 and then from grade 10 through 3 years after high school completion (at age 21 years). Surveys were conducted from March 2013 through November 2021.InterventionAttendance at a high-performing public charter high school.Main outcomes and measuresSelf-reported alcohol use disorder and cannabis misuse, delinquent behaviors, physical and mental health, and body mass index.ResultsOf the 1270 participants at baseline (mean [SD] age, 14.2 [0.47] years; 668 female individuals [52.6%]). The control group included 576 individuals (45.4%), and 694 individuals (54.6%) were in the intervention group. Both groups were similar in almost all characteristics at baseline, and the median (IQR) follow-up was 6.4 (6.0-6.7) years. Participants attending a high-performing public charter high school had a 53.33% lower rate of hazardous or dependent alcohol use disorder compared with those in the control group (5.43% vs 11.64%; difference, -6.21% [95% CI, -11.87% to -0.55%]; P = .03). Among male participants, the intervention group had a 42.05% lower rate of self-reported fair or poor physical health (13.33% vs 23.01%; difference, -9.67% [95% CI, -18.30% to -1.05%]; P = .03) and a 32.94% lower rate of obesity or overweight (29.28% vs 43.67%; difference, -14.38% [95% CI, -25.74% to -3.02%]; P = .02) compared with the control group. Among female participants, attending a high-performing public charter high school was associated with worse physical health outcomes (30.29% vs 13.47% reporting fair or poor health; difference, 16.82% [95% CI, 0.36% to 33.28%]; P = .045) and higher rates of overweight or obesity (52.20% vs 32.91%; difference, 19.30% [95% CI, 3.37% to 35.22%]; P = .02) at age 21 years. Few differences in mental health outcomes were observed. Adjusting for educational outcomes did not significantly change these findings.Conclusions and relevanceResults of this study suggest that attending a high-performing public charter high school was associated with lower rates of substance use disorder independent of academic achievement. Physical health and obesity outcomes were also better but only for young men; the intervention group had worse physical health outcomes among young women for unclear reasons. Schools are a potent social determinant of health and an important target for future health interventions.

Increasing resident and fellow independence as they progress through training is a cornerstone of medical education. Medical educators and trainees perceive many benefits from resident/fellow autonomy, including increased confidence and [...], * Context.--Progressive independence in medicine is critical to building confidence and decisiveness in trainees. However, this can be difficult to accomplish in the strict regulatory environment of pathology. Objective.--To pilot and adopt a process whereby surgical pathology fellows independently manage a subset of cases and release preliminary reports. Design.--Upon program approval, board-certified surgical pathology fellows were eligible for preliminary report sign-out at their discretion. Eligible cases were sent from outside institutions for confirmatory review. Preliminary reports were viewable in the electronic medical record. Safety measures were used to ensure timely release of final reports by attending pathologists. Results.--Fellows participating in the pilot (n = 4) released 59 preliminary reports out of 101 cases reviewed (58%), with 1 potentially significant discrepancy between preliminary and final report. Turnaround time was not affected. The process was endorsed by all participants and adopted as standard practice. During the first year, eligible fellows (n = 8) released 123 preliminary reports out of 1260 cases reviewed (9.8%). There were no major diagnostic discrepancies and no effects on turnaround time. The number of preliminary reports released by each fellow was variable (range, 2-48; median, 8), likely a reflection of both external factors (number of trainees on service, volume) and trainee-specific factors (confidence, efficiency). Conclusions.--Fellows showed good judgment when independently managing cases, with just 1 potentially significant discrepancy out of 182 cases ( doi: 10.5858/arpa.2022-0223-OA

Adolescence is a critical transition period that sets the stage for adulthood and future health outcomes. Marked by key developmental milestones in brain maturation, increasing independence from parents, and greater connections to peers, adolescence is also a time of heightened risk for behavioral health problems, including substance use, violence, delinquency, and mental health issues. High school completion is a significant life course event and a powerful social determinant of health and health disparities. Jessor's Theory of Problem Behavior suggests that adolescent health behaviors and mental health problems are closely tied to poor educational outcomes and peer network formation in a reinforcing feedback loop, or vicious cycle, often leading to school failure, school disengagement, and drop-out. Schools are a novel platform through which vicious cycles can be disrupted and replaced with virtuous ones, simultaneously improving education and health. This article describes the potential for schools to transform health trajectories through interventions creating positive and supportive school climates. In addition, new models such as the Whole School Whole Community Whole Child Model promote whole child well-being, including cognitive, social, emotional, psychological, and physical development. Full-service community schools can serve as a hub coordinating and integrating all available resources to better respond to the needs of children and families. Present in every neighborhood, schools are a way to reach every school-age child and improve their health trajectories, providing an important platform for life course intervention research.