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COVID-19 vaccine uptake remains low for US adolescents and contributes to excess morbidity and mortality. Most research has assessed parental intention to vaccinate their children. We explored differences between vaccine-acceptant and vaccine-hesitant unvaccinated US adolescents using national survey data. A nonprobability, quota-based sample of adolescents, aged 13–17 years, was recruited through an online survey panel in April 2021. One thousand nine hundred twenty seven adolescents were screened for participation and the final sample included 985 responses. We assessed responses from unvaccinated adolescents (n = 831). Our primary measure was COVID-19 vaccination intent ("vaccine-acceptant" defined as "definitely will" get a COVID-19 vaccine and any other response classified as "vaccine-hesitant") and secondary measures included reasons for intending or not intending to get vaccinated and trusted sources of COVID-19 vaccine information. We calculated descriptive statistics and chi-square tests to explore differences between vaccine-acceptant and vaccine-hesitant adolescents. Most (n = 831; 70.9%) adolescents were hesitant, with more hesitancy observed among adolescents with low levels of concern about COVID-19 and high levels of concern about side effects of COVID-19 vaccination. Among vaccine-hesitant adolescents, reasons for not intending to get vaccinated included waiting for safety data and having parents who would make the vaccination decision. Vaccine-hesitant adolescents had a lower number of trusted information sources than vaccine-acceptant adolescents. Differences identified between vaccine-acceptant and vaccine-hesitant adolescents can inform message content and dissemination. Messages should include accurate, age-appropriate information about side effects and risks of COVID-19 infection. Prioritizing dissemination of these messages through family members, state and local government officials, and healthcare providers may be most effective. [ABSTRACT FROM AUTHOR]

Innovative strategies are needed to improve pediatric COVID-19 vaccination rates. We describe the process for developing a clinic-based intervention, CONFIDENCE, to improve pediatric COVID-19 vaccine uptake and present results of our beta-test for feasibility and acceptability. CONFIDENCE included communication training with providers, a poster campaign, and parent-facing educational materials. We assessed feasibility and acceptability through interviews and measured preliminary vaccine intention outcomes with a pre-post parent survey. Interviews were analyzed using rapid qualitative methods. We generated descriptive statistics for variables on the parent survey and used Fisher's exact test to assess pre-post differences. Participating providers (n = 4) reported high levels of feasibility and acceptability. We observed positive trends in parents' (n = 69) reports of discussing vaccination with their provider and the parental decision to accept COVID-19 vaccination. Our next steps will be to use more rigorous methods to establish the efficacy and effectiveness of the CONFIDENCE intervention. [ABSTRACT FROM AUTHOR]

• O-POCUS enables early identification of conditions like of fetal presentation, multiple gestation, and placental issues, leading to timely interventions. • The findings show the role of O-POCUS in enhancing clinical decision-making and service quality, in lower level facilities in LMICs. • This paper contributes insights from diverse HCPs, to the understanding of O-POCUS implementation in LMICs, emphasizing the need for comprehensive strategies to improve maternal care. Ultrasound technology has become integral in antenatal care for its diagnostic effectiveness and potential to improve maternal and neonatal outcomes. Despite its proven benefits, challenges persist in its widespread adoption, particularly in low-resource settings like Kenya. Aim: The aim of this study was to explore the perspectives of healthcare providers regarding the integration of obstetric point-of-care ultrasound into routine maternal services in low-level facilities Kenya. Using a descriptive qualitative study embedded in a large scale implementation study 76 healthcare providers who had undergone obstetric point-ofcare ultrasound training and were providing maternal services were purposively sampled from healthcare facilities across eight counties. Data was collected using structured audiotaped interviews, which were transcribed, and analyzed using thematic analysis. Five main themes with several subthemes emerged from the analysis: (1) Clinical Decision-Making (2) Quality of Services, (3) Training, (4)Technology Issues, and (5) Sustainability. Findings from this study suggest that use of obstetric Point-of-Care Ultrasound in resource-limited primary care settings, can enhance clinical decision making and influence patient management, ultimately resulting in significant health outcomes. Equipping health care providers with skills to conduct obstetric point of care ultrasound can lead to better-informed clinical decisions and ultimately contribute to improved health outcomes in underserved populations. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the effect of an acute bout of circuit-base exercise on executive function, visual perception and sleep parameters in neurodiverse children. After familiarisation, 34 children (4 female) with ADHD and/or ASD completed two trials (30-min circuit-based exercise (E) or a rested control (C) trial) in a randomised, counterbalanced, crossover design. Participants completed cognitive function tests (Stroop test, Sternberg Paradigm and Visual Search Test) at baseline, immediately post-exercise, and the morning after exercise. Participants were provided with a wrist actigraph to wear overnight to determine sleep duration, wake after sleep onset, sleep efficiency, and sleep latency. Statistical analyses were conducted via ANCOVA, with diagnosis included as a covariate. Accuracy on the Stroop test (complex level) was better maintained following circuit-based exercise when compared with rest immediately post-exercise (E: 1.88% decreased accuracy; C: 4.73% decreased accuracy, p = 0.009), and on day two (E: 1.22% increased accuracy; C: 6.37% decreased accuracy; p < 0.001). Accuracy on the Sternberg Paradigm (5-item level) was improved immediately post-exercise on the exercise trial when compared with rest (E: 0.37% decreased accuracy; C: 7.29% decreased accuracy; p = 0.011). Improvements in accuracy across both tests were at the expense of response time, which was slower on the exercise trial (all p < 0.05). Sleep parameters did not differ across trials (all p > 0.05). Moderate intensity circuit-based exercise is an ecologically valid exercise modality that, acutely, improves executive function (compared to rest), which may alleviate the impaired executive function in children with ADHD and ASD. • Examined acute effect of circuit-based exercise on cognition in ADHD/ASD children. • Improved inhibitory control and working memory in neurodiverse children. • Improved executive function occurred immediately post-exercise and into day two. • Neurodiverse children were happier following the circuit-based exercise. • Circuit-based exercise could be used to manage common symptoms of ADHD/ASD. [ABSTRACT FROM AUTHOR]

Background: Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.Objective: To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.Methods: This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.Results: Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]>1.5, FDR<.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH>1.3, FDR<.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r>.6; P <.05).Limitations: This study was limited by a small sample size and predominantly female FFA patients.Conclusion: Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition. [ABSTRACT FROM AUTHOR]

Background: Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.Objective: To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.Methods: In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).Results: Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.Limitations: Our analysis was limited to 350 proteins.Conclusion: This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches. [ABSTRACT FROM AUTHOR]

Ketamine has rapid-acting antidepressant properties but also potentially concerning transient dissociative side effects (SEs). Recent studies noted a positive correlation between treatment response to ketamine and general dissociative SEs, as well as "floating", a depersonalization SE (a subtype of the dissociative SEs). This analysis sought to determine whether floating mediates treatment response to ketamine. Data were pooled from three double-blind, crossover, placebo-controlled ketamine clinical trials across which 82 participants with treatment-resistant depression (TRD) (44 with bipolar depression and 38 with major depressive disorder) received placebo and ketamine (0.5 mg/kg) infusions. SEs were actively solicited in a standardized fashion before and after ketamine infusion. The hypothesis that a post-infusion experience of floating would mediate antidepressant response to ketamine was assessed at 230 min post-infusion and at Day 1. Montgomery-Asberg Depression Rating Scale (MADRS) total score was the dependent variable in a linear mixed effects model. Ketamine significantly decreased MADRS scores (p < 0.0001), but no relationship was detected between floating and MADRS score at either 230 min or Day 1 post-infusion. The hypothesized mediation effect of floating was also not detected at either 230 min or Day 1 post-infusion. Taken together, the findings do not support the hypothesis that ketamine's antidepressant effects are mediated by the dissociative depersonalization subtype SE of floating. • Antidepressant response to ketamine may be related to dissociative symptoms. • Floating (or feeling of lightness) is a specific dissociative side effect. • Patients (n = 82) with treatment-resistant depression received placebo and ketamine. • Ketamine's antidepressant effects were not mediated by the symptom of floating. • The specific dissociative symptom of floating does not predict response to ketamine. [ABSTRACT FROM AUTHOR]

Background: Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects.Objective: To assess the safety and efficacy of crisaborole 2% ointment-a nonsteroidal phosphodiesterase 4 inhibitor-in the treatment of intertriginous, anogenital, and facial psoriasis.Methods: A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS).Results: After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events.Limitations: The study was limited to a single tertiary care center and small sample size.Conclusion: Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis. [ABSTRACT FROM AUTHOR]

Connecting neural activity to function is a common aim in neuroscience. How to define and conceptualize function, however, can vary. Here I focus on grounding this goal in the specific question of how a given change in behavior is produced by a change in neural circuits or activity. Artificial neural network models offer a particularly fruitful format for tackling such questions because they use neural mechanisms to perform complex transformations and produce appropriate behavior. Therefore, they can be a means of causally testing the extent to which a neural change can be responsible for an experimentally observed behavioral change. Furthermore, because the field of interpretability in artificial intelligence has similar aims, neuroscientists can look to interpretability methods for new ways of identifying neural features that drive performance and behaviors. [ABSTRACT FROM AUTHOR]

Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA)+ T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo. We sought to measure cytokine production by circulating skin-homing (CLA+) versus systemic (CLA−) "polar" CD4+/CD8+ ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects. Flow cytometry was used to measure levels of the cytokines IFN-γ, IL-13, IL-9, IL-17, and IL-22 in CD4+/CD8+ T cells in the blood of 19 patients with moderate-to-severe nonsegmental/generalized vitiligo, moderate-to-severe AA (n = 32), psoriasis (n = 24), or AD (n = 43) and control subjects (n = 30). Unsupervised clustering differentiated subjects into groups based on cellular frequencies. Patients with Vitiligo showed the highest CLA+/CLA− T H 1/type 1 cytotoxic T-cell polarization, with parallel T H 2/T H 9/T H 17/T H 22 level increases to levels often greater than those seen in patients with AA, AD, or psoriasis (P <.05). Total regulatory T-cell counts were lower in patients with vitiligo than in control subjects and patients with AD or psoriasis (P <.001). Vitiligo severity correlated with levels of multiple cytokines (P <.1), whereas duration was linked with IFN-γ and IL-17 levels (P <.04). Patients and control subjects grouped into separate clusters based on blood biomarkers. Vitiligo is characterized by a multicytokine polarization among circulating skin-homing and systemic subsets, which differentiates it from other inflammatory/autoimmune skin diseases. Future targeted therapies should delineate the relative contribution of each cytokine axis to disease perpetuation. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) frequently exhibit language delays and functional communication deficits. Pivotal response treatment (PRT) is an effective intervention for targeting these skills; however, similar to other behavioral interventions, response to PRT is variable across individuals. Thus, objective markers capable of predicting treatment response are critically-needed to identify which children are most likely to benefit from this intervention. In this pilot study, we investigated whether structural neuroimaging measures from language regions in the brain are associated with response to PRT. Children with ASD (n = 18) who were receiving PRT to target their language deficits were assessed with MRI at baseline. T1-weighted images were segmented with FreeSurfer and morphometric measures of the primary language regions (inferior frontal (IFG) and superior temporal (STG) gyri) were evaluated. Children with ASD and language deficits did not exhibit the anticipated relationships between baseline structural measures of language regions and baseline language abilities, as assessed by the number of utterances displayed during a structured laboratory observation (SLO). Interestingly, the level of improvement on the SLO was correlated with baseline asymmetry of the IFG, and the size of the left STG at baseline was correlated with the level of improvement on standardized parental questionnaires. Although very preliminary, the observed associations between baseline structural properties of language regions and improvement in language abilities following PRT suggest that neuroimaging measures may be able to help identify which children are most likely to benefit from specific language treatments, which could help improve precision medicine for children with ASD. [ABSTRACT FROM AUTHOR]

Abstract Microorganisms can acquire energy from the environment by extending their electron transport chains to external solid electron donors or acceptors. This process, known as extracellular electron transfer (EET), is now being heavily pursued for wiring microbes to electrodes in bioelectrochemical renewable energy technologies. Recent studies highlight the crucial role of multi-heme cytochromes in facilitating biotic–abiotic EET both for cellular electron export and uptake. Here we explore progress in understanding the range and function of these biological electron conduits in the context of fuel-to-electricity and electricity-to-bioproduct conversion. We also highlight emerging topics, including the role of multi-heme cytochromes in inter-species electron transfer and in inspiring the design and synthesis of a new generation of protein-based bioelectronic components. [ABSTRACT FROM AUTHOR]

Background Several single-center studies have suggested that eliminating contact precautions (CPs) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) control in nonoutbreak settings has no impact on infection rates. We performed a systematic literature review and meta-analysis on the impact of discontinuing contact precautions in the acute care setting. Methods We searched PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Embase through December 2016 for studies evaluating discontinuation of contact precautions for multidrug-resistant organisms. We used random-effect models to obtain pooled risk ratio estimates. Heterogeneity was evaluated with I 2 estimation and the Cochran Q statistic. Pooled risk ratios for MRSA and VRE were assessed separately. Results Fourteen studies met inclusion criteria and were included in the final review. Six studies discontinued CPs for both MRSA and VRE, 3 for MRSA only, 2 for VRE only, 2 for extended-spectrum β-lactamase–producing Escherichia coli , and 1 for Clostridium difficile infection. When study results were pooled, there was a trend toward reduction of MRSA infection after discontinuing CPs (pooled risk ratio, 0.84; 95% confidence interval, 0.70-1.02; P  = .07) and a statistically significant reduction in VRE infection (pooled risk ratio, 0.82; 95% confidence interval, 0.72-0.94; P  = .005). Conclusions Discontinuation of CPs for MRSA and VRE has not been associated with increased infection rates. [ABSTRACT FROM AUTHOR]

Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. A total of 84 pregnant women with obesity (body mass index > 30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O 2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O 2 saturation, and O 2 saturation variability) were analyzed as potential moderators using linear mixed effects models. A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O 2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus. [ABSTRACT FROM AUTHOR]

Objectives: To compare acute care virtual visits with in-person visits with respect to equity of access, markers of quality and safety, and parent and provider experience, before and during the COVID-19 pandemic.Study Design: We compared patient demographics, antimicrobial prescribing rates, ED utilization, and patient-experience scores for virtual visits and in-person care at two academic pediatric primary care practices using chi-square testing and interrupted time series analyses. Parent and provider focus groups explored themes related to virtual visit experience and acceptability.Results: We compared virtual acute care visits conducted in March 2020-February 2021 (n=8,868) with in-person acute care visits conducted in February 2019-March 2020 (n= 24,120) and March 2020-February 2021 (n=6,054). There were small differences in patient race/ethnicity across the different cohorts (p<0.01). Virtual visits were associated with a 9.6% (-11.5%, -7.8%, p<0.001) decrease in all antibiotic prescribing and a 13.2% (-22.1%, -4.4%, p<0.01) decrease in antibiotic prescribing for acute respiratory tract infections. Unanticipated ED visits did not significantly differ among visit types. Patient experience scores were significantly higher (p<0.05) for virtual acute care in overall rating of care and likelihood to recommend. Focus group themes included safety, distractibility, convenience, treatment, and technology. Providers were broadly accepting of virtual care while parental views were more mixed.Conclusion: Telehealth acute care visits may not have negative effects on quality and safety, as measured by antimicrobial prescribing and unanticipated ED visit rates. Efforts to increase parental acceptance and avoid creating disparities in access to virtual care will be essential to continued success of telehealth acute care visits. [ABSTRACT FROM AUTHOR]

Using discriminant analysis, we trace the US bank failures during the period from 2007 to 2010 to poor investment decisions and large exposure to systemic risk channels. Specifically, we find that the proportion of illiquid loans in their books and the exposure to the interbank funding markets are the main predictors of bank failures. There are indicators that distinguish surviving banks from their failed peers, and these indicators serve as the early warning signals that predict banking failures. This study provides regulators and bank management forecast signals of financial exigency. [ABSTRACT FROM AUTHOR]

Though an emerging evidence base has documented the elevated stress and unique challenges among parents of autistic children, less is known about resilience. Based on the resilience-stress model (Fletcher & Sarkar, 2013 ; Masten, 2011), resilience may be a promising area of investigation given its inverse relationship with stress. Fifty parents of autistic children (4:0–10:11 years) self-reported resilience on the Connor-Davidson Resilience Scale (CD-RISC) and completed additional questionnaires, which were categorized into three classes of predictors: psychological functioning, child factors and parenting stress, and positive mental health practices. Regression analyses were conducted to identify the amount of variance in CD-RISC scores explained by the overall model and each class of predictors. The relative strength of individual predictors was investigated. The overall model accounted for 66% of the variance in self-reported resilience scores. Two classes of predictors were significant – psychological functioning and positive mental health practices – while child factors and parenting stress were not. Specifically, the class of psychological functioning variables accounted for 45% of the variance in resilience scores and positive mental health practices accounted for an additional 19%. The individual predictors of anxiety, stress, optimism, and self-compassion were the most robust. Findings indicate that certain factors – anxiety, stress, optimism, and self-compassion – are important in understanding self-reported resilience among some parents of autistic children. This may suggest treatment targets for resilience interventions. Continued investigations with larger, more representative samples are needed to expand the present findings. • Certain classes of variables were associated with self-reported resilience in some parents of autistic children. • Anxiety, stress, optimism, and self-compassion were robust predictors of parental self-reported resilience. • Child problem behaviors and parent mindfulness were not correlated with parental resilience in this sample. • Findings reveal important treatment targets for parents of autistic children. [ABSTRACT FROM AUTHOR]

Summary: Early diagnosis of active tuberculosis (TB) remains an elusive challenge, especially in individuals with disseminated TB and HIV co-infection. Recent studies have shown a promise for the direct detection of pathogen-specific biomarkers such as lipoarabinomannan (LAM) for the diagnosis of TB in HIV-positive individuals. Currently, traditional immunoassay platforms that suffer from poor sensitivity and high non-specific interactions are used for the detection of such biomarkers. In this manuscript, we demonstrate the development of sandwich immunoassays for the direct detection of three TB-specific biomarkers, namely LAM, early secretory antigenic target 6 (ESAT6) and antigen 85 complex (Ag85), using a waveguide-based optical biosensor platform. Combining detection within the evanescent field of a planar optical waveguide with functional surfaces that reduce non-specific interactions allows for the ultra-sensitive and quantitative detection of biomarkers (an order of magnitude enhanced sensitivity, as compared to plate-based ELISA) in complex patient samples (urine, serum) within a short time. We also demonstrate the detection of LAM in urine from a small sample of subjects being treated for TB using this approach with excellent sensitivity and 100% corroboration with disease status. These results suggest that pathogen-specific biomarkers can be applied for the rapid and effective diagnosis of disease. It is likely that detection of a combination of biomarkers offers greater reliability of diagnosis, rather than detection of any single pathogen biomarker. NCT00341601. [ABSTRACT FROM AUTHOR]

Summary: The thioredoxin family of oxidoreductases plays an important role in redox signaling and control of protein function. Not only are thioredoxins linked to a variety of disorders, but their stable structure has also seen application in protein engineering. Both sequence-based and structure-based tools exist for thioredoxin identification, but remote homolog detection remains a challenge. We developed a thioredoxin predictor using the approach of integrating sequence with structural information. We combined a sequence-based Hidden Markov Model (HMM) with a molecular dynamics enhanced structure-based recognition method (dynamic FEATURE, DF). This hybrid method (HMMDF) has high precision and recall (0.90 and 0.95, respectively) compared with HMM (0.92 and 0.87, respectively) and DF (0.82 and 0.97, respectively). Dynamic FEATURE is sensitive but struggles to resolve closely related protein families, while HMM identifies these evolutionary differences by compromising sensitivity. Our method applied to structural genomics targets makes a strong prediction of a novel thioredoxin. [ABSTRACT FROM AUTHOR]

Summary: Sleep duration in the population has been declining. Women occupy an increasingly prominent place in the work force without reducing most of their responsibilities at home. Consequently, sleep needs are often pushed to the bottom of women''s daily priority list. Prior research has indicated that sleep deprivation is associated with higher levels of pro-inflammatory serum cytokines. This is important because higher plasma concentrations of pro-inflammatory serum cytokine levels are associated with postpartum depression and adverse birth outcomes such as preterm delivery. However, little research has directly examined how sleep deprivation may affect maternal and fetal outcomes. This review summarizes the existing data on the effect of sleep deprivation during pregnancy on maternal and fetal outcomes. We review supporting evidence for the hypotheses that sleep deprivation during pregnancy increases the risk of preterm delivery and postpartum depression, and that systemic inflammation is the causal mechanism in the association. Prior research on sleep in pregnancy has been limited by varying data collection methods, subjective self-reported sleep measures, small and non-representative samples, cross-sectional designs; descriptive or non-hypothesis driven studies. Future research with longitudinal study designs is needed to allow examination of the effect of sleep deprivation on adverse maternal and fetal outcomes. [Copyright &y& Elsevier]

Background: Antibody-mediated rejection (AMR) has been associated with poor outcome after heart transplantation. The diagnosis of AMR usually includes endomyocardial biopsy findings of endothelial cell swelling, intravascular macrophages, C4d+ staining, and associated left ventricular dysfunction. The significance of AMR findings in biopsy specimens of asymptomatic heart transplant patients (normal cardiac function and no symptoms of heart failure) is unclear. Methods: Between July 1997 and September 2001, AMR was found in the biopsy specimens of 43 patients. Patients were divided into 2 groups: asymptomatic AMR (AsAMR, n = 21) and treated AMR (TxAMR with associated left ventricular dysfunction, n = 22). For comparison, a control group of 86 contemporaneous patients, without AMR, was matched for age, gender, and time from transplant. Outcomes included 5-year actuarial survival and development of cardiac allograft vasculopathy (CAV). Patients were considered to have AMR if they had ≥ 1 endomyocardial biopsy specimen positive for AMR. Results: The 5-year actuarial survival for the AsAMR (86%), TxAMR (68%), and control groups (79%) was not significantly different (p = 0.41). Five-year freedom from CAV (≥ 30% stenosis in any vessel) was AsAMR, 52%; TxAMR, 68%; and control, 79%. Individually, freedom from CAV was significantly lower in the AsAMR group compared with the control group (p = 0.02). There was no significant difference between AsAMR vs TxAMR and TxAMR vs control for CAV. Conclusions: Despite comparable 5-year survival with controls after heart transplantation, AsAMR rejection is associated with a greater risk of CAV. Trials to treat AsAMR to alter outcome are warranted. [Copyright &y& Elsevier]

Abstract: Soft tissue signs are inadequate to assess pulpal anesthesia during root canal therapy (RCT). The intention of this study was to determine if a negative response to cold testing is a more effective measure to assess pulpal anesthesia compared to soft tissues signs. Using a randomized, blinded, placebo-controlled design, subjects with baseline responsiveness to cold testing were enrolled. Test subjects achieved a negative response to cold testing prior to RCT. Control subjects were given a sham cold test after demonstrating soft tissue signs. Visual analog scale determined pain level. Unadjusted results showed 12% of test subjects experienced pain during RCT compared with 38% of control subjects (N = 83, p = .004, power = 84%). Multiple logistic regression controlled for confounders and effect modifiers, OR = .20 (p = .01). Subjects who achieved a negative response to the cold test were approximately 80% less likely to experience pain during RCT compared to subjects with soft tissue signs of anesthesia alone. [Copyright &y& Elsevier]

Background Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. Objectives The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. Study Design Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6–15 weeks gestation) and mid pregnancy (22–31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. Results Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. Conclusion Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials. [ABSTRACT FROM AUTHOR]

Background: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes.Objective: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy.Study Design: This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes.Results: In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes.Conclusion: Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women. [ABSTRACT FROM AUTHOR]

Objective: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes.Study Design: NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized level 3 home sleep test was performed between 6(0)-15(0) weeks' gestation (visit 1) and again between 22(0)-31(0) weeks' gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met "urgent referral" criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth.Results: Objective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on 2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported in this methods article.Conclusion: The substudy was designed to address important questions regarding the relationship of sleep-disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health. [ABSTRACT FROM AUTHOR]

Despite the potential for improved patient care, little is known of the true effect of point-of-care ultrasound (POCUS) on patient outcomes in resource-limited settings. Electronic databases were searched using medical subject heading and free text terms related to POCUS and resource-limited settings through August 2020. Two authors independently selected studies, assessed methodological quality using the Downs and Black scale and extracted data. Twenty observational studies were included in the final review. All studies had moderate to high risk of bias. No studies exhibited an effect on the pre-specified primary outcome of mortality. Varying degrees of change in differential diagnosis and management were reported, but definitions varied widely among studies. Estimates for change in diagnosis as a result of POCUS ranged from 15% to 52%, and those for change in management, from 17% to 87%. Articles on POCUS clinical utility represent a small part (4.6%) of the scholastic literature dedicated to POCUS in low-resource settings. POCUS is a valuable intervention to consider in resource-limited settings, with the potential to change diagnosis and patient management. The exact magnitude of effect remains unknown. There is a continued need for large-scale experimental studies to investigate the effect of POCUS on patient diagnosis, management and mortality. [ABSTRACT FROM AUTHOR]