Evaluation of different mucosal microbiota leads to gut microbiota-based prediction of type 1 diabetes in NOD mice

Type 1 diabetes (T1D) is a progressive autoimmune disease in which the insulin-producing beta cells are destroyed by auto-reactive T cells. Recent studies suggest that microbiota are closely associated with disease development. We studied gut, oral and vaginal microbiota longitudinally in non-obese diabetic (NOD) mice. We showed that the composition of microbiota is very different at the different mucosal sites and between young and adult mice. Gut microbiota are more diverse than oral or vaginal microbiota and the changes were more evident in the mice before and after onset of diabetes. Using alpha-diversity, Gram-positive/Gram-negative ratio as well as the relative abundance of Bacteroidetes and Erysipelotrichaceae in the gut microbiota, at 8 weeks of age, we formulated a predictive algorithm for T1D development in a cohort of 63 female NOD mice. Using this algorithm, we obtained 80% accuracy of prediction of diabetes onset, in two independent experiments, totaling 29 mice, with Area Under the Curve of 0.776 by ROC analysis. Interestingly, we did not find differences in peripheral blood mononuclear cells of the mice at 8 weeks of age, regardless of later diabetes development. Our results suggest that the algorithm could potentially be used in early prediction of future T1D development

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children

AbstractBackgroundPreterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections.MethodsLongitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n=13) compared to T children (n=12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group×age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test—revised (PPVT­R), and Rapid Naming Composite (RDRL_Cmp).ResultsNine regions were generated by the group×age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time.ConclusionsThese findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC

Racial and ethnic differences in internal medicine residency assessments

IMPORTANCE: Previous studies have demonstrated racial and ethnic inequities in medical student assessments, awards, and faculty promotions at academic medical centers. Few data exist about similar racial and ethnic disparities at the level of graduate medical education. OBJECTIVE: To examine the association between race and ethnicity and performance assessments among a national cohort of internal medicine residents. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated assessments of performance for 9026 internal medicine residents from the graduating classes of 2016 and 2017 at Accreditation Council of Graduate Medical Education (ACGME)-accredited internal medicine residency programs in the US. Analyses were conducted between July 1, 2020, and June 31, 2022. MAIN OUTCOMES AND MEASURES: The primary outcome was midyear and year-end total ACGME Milestone scores for underrepresented in medicine (URiM [Hispanic only; non-Hispanic American Indian, Alaska Native, or Native Hawaiian/Pacific Islander only; or non-Hispanic Black/African American]) and Asian residents compared with White residents as determined by their Clinical Competency Committees and residency program directors. Differences in scores between Asian and URiM residents compared with White residents were also compared for each of the 6 competency domains as supportive outcomes. RESULTS: The study cohort included 9026 residents from 305 internal medicine residency programs. Of these residents, 3994 (44.2%) were female, 3258 (36.1%) were Asian, 1216 (13.5%) were URiM, and 4552 (50.4%) were White. In the fully adjusted model, no difference was found in the initial midyear total Milestone scores between URiM and White residents, but there was a difference between Asian and White residents, which favored White residents (mean [SD] difference in scores for Asian residents: -1.27 [0.38]; P \u3c .001). In the second year of training, White residents received increasingly higher scores relative to URiM and Asian residents. These racial disparities peaked in postgraduate year (PGY) 2 (mean [SD] difference in scores for URiM residents, -2.54 [0.38]; P \u3c .001; mean [SD] difference in scores for Asian residents, -1.9 [0.27]; P \u3c .001). By the final year 3 assessment, the gap between White and Asian and URiM residents\u27 scores narrowed, and no racial or ethnic differences were found. Trends in racial and ethnic differences among the 6 competency domains mirrored total Milestone scores, with differences peaking in PGY2 and then decreasing in PGY3 such that parity in assessment was reached in all competency domains by the end of training. CONCLUSIONS AND RELEVANCE: In this cohort study, URiM and Asian internal medicine residents received lower ratings on performance assessments than their White peers during the first and second years of training, which may reflect racial bias in assessment. This disparity in assessment may limit opportunities for physicians from minoritized racial and ethnic groups and hinder physician workforce diversity

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study

Background: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams (‘First-episode Services’ or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? Methods/Design The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREPR) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREPR over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. Discussion STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. Trial registration ClinicalTrials.gov: NCT02069925. Registered 20 February 2014

Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children.

BACKGROUND: The optimal treatment of malaria in human immunodeficiency virus (HIV)-infected children requires consideration of critical drug-drug interactions in coinfected children, as these may significantly impact drug exposure and clinical outcomes. METHODS: We conducted an intensive and sparse pharmacokinetic/pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on 3 different first-line antiretroviral therapy (ART) regimens were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin, and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated. RESULTS: One hundred forty-five and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared with no ART, efavirenz (EFV) reduced exposure to all antimalarial components by 2.1- to 3.4-fold; lopinavir/ritonavir (LPV/r) increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on EFV vs LPV/r-based ART, changes that were associated with an approximate 4-fold higher odds of recurrent malaria by day 28 in those on EFV vs LPV/r-based ART. CONCLUSIONS: The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. EFV-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on EFV, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure, is warranted

Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial

BackgroundCurrent therapies for obesity treatment are effective at producing short-term weight loss, but weight loss maintenance remains a significant challenge. Here we investigate the impact of pre-intervention dietary fat intake on the efficacy of a dietary supplement to support weight loss maintenance. Preclinical work demonstrates that a vagal afferent pathway critical for sensing dietary lipids is blunted by a high-fat diet (HFD), resulting in a reduced preference for a low-fat emulsion and severe blunting of the dopamine (DA) response to the gastric infusion of lipids. Infusion of the gut lipid messenger oleoylethanolamide (OEA), which is also depleted by HFD, immediately reverses this DA blunting and restores preference for the low-fat emulsion. Studies of OEA supplementation for weight loss in humans have had limited success. Given the strong effect of HFD on this pathway, we designed a study to test whether the efficacy of OEA as a weight loss treatment is related to pre-intervention habitual intake of dietary fat.Methods/DesignWe employed a randomized, double-blind, placebo-controlled trial in which 100 adults with overweight/obesity (OW/OB) were randomized to receive either OEA or placebo daily for 16 months. Following a baseline evaluation of diet, metabolic health, adiposity, and brain response to a palatable an energy dense food, participants in both groups underwent a 4-month behavioral weight loss intervention (LEARN®) followed by a 1-year maintenance period. The study aims are to (1) determine if pre-intervention dietary fat intake moderates the ability of OEA to improve weight loss and weight loss maintenance after a gold standard behavioral weight loss treatment; (2) identify biomarkers that predict outcome and optimize a stratification strategy; and (3) test a model underlying OEA’s effectiveness.DiscussionFocusing on interventions that target the gut-brain axis is supported by mounting evidence for the role of gut-brain signaling in food choice and the modulation of this circuit by diet. If successful, this work will provide support for targeting the gut-brain pathway for weight loss maintenance using a precision medicine approach that is easy and inexpensive to implement.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04614233]

Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection

Introduction Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. Methods and findings We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV- 2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). Conclusions In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms

A New Method for Crop Row Detection Using Unmanned Aerial Vehicle Images

Crop row detection using unmanned aerial vehicle (UAV) images is very helpful for precision agriculture, enabling one to delineate site-specific management zones and to perform precision weeding. For crop row detection in UAV images, the commonly used Hough transform-based method is not sufficiently accurate. Thus, the purpose of this study is to design a new method for crop row detection in orthomosaic UAV images. For this purpose, nitrogen field experiments involving cotton and nitrogen and water field experiments involving wheat were conducted to create different scenarios for crop rows. During the peak square growth stage of cotton and the jointing growth stage of wheat, multispectral UAV images were acquired. Based on these data, a new crop detection method based on least squares fitting was proposed and compared with a Hough transform-based method that uses the same strategy to preprocess images. The crop row detection accuracy (CRDA) was used to evaluate the performance of the different methods. The results showed that the newly proposed method had CRDA values between 0.99 and 1.00 for different nitrogen levels of cotton and CRDA values between 0.66 and 0.82 for different nitrogen and water levels of wheat. In contrast, the Hough transform method had CRDA values between 0.93 and 0.98 for different nitrogen levels of cotton and CRDA values between 0.31 and 0.53 for different nitrogen and water levels of wheat. Thus, the newly proposed method outperforms the Hough transform method. An effective tool for crop row detection using orthomosaic UAV images is proposed herein

Location-aware spectrum sharing in cognitive radio networks - A semi-matching approach

Cognitive radio can improve the spectrum efficiency by allowing multiple secondary users to access the idle licensed spectrum, for which efficient and fair spectrum sharing is one of the key challenges. In this paper, we investigate the multiuser multi-channel spectrum allocation problem in cognitive radio networks with the objective of maximizing the minimum throughput among all the cognitive pairs. In the proposed approach, all the secondary users will get the opportunity to access the channel and thus a good fairness can be achieved. We first introduce a weighted bipartite graph model for this design problem. A novel semi-matching based framework is then proposed to provide an efficient suboptimal solution, which only requires statistical channel state information. Simulation results will show that by applying this approach, max-min fairness can be improved for the secondary users