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BACKGROUND: Hispanic ethnic density (HED) is a marker of better health outcomes among Hispanic patients with chronic disease. It is unclear whether community HED is associated with mortality risk among ethnically diverse patients receiving maintenance hemodialysis. METHODS: A retrospective analysis of patients in the United States cohort of the Dialysis Outcomes and Practice Patterns Study (DOPPS) database (2011-2015) was conducted (n = 4226). DOPPS data was linked to the American Community Survey database by dialysis facility zip code to obtain % Hispanic residents (HED). One way ANOVA and Kruskal Wallis tests were used to estimate the association between tertiles of HED with individual demographic, clinical and adherence characteristics, and facility and community attributes. Multivariable Cox proportional hazards models were used to estimate the mortality hazard ratio (HR) and 95% CIs by tertile of HED, stratified by age; a sandwich estimator was used to account for facility clustering. RESULTS: Patients dialyzing in facilities located in the highest HED tertile communities were younger (61.4 vs. 64.4 years), more commonly non-White (62.4% vs. 22.1%), had fewer comorbidities, longer dialysis vintage, and were more adherent to dialysis treatment, but had fewer minutes of dialysis prescribed than those in the lowest tertile. Dialyzing in the highest HED tertile was associated with lower hazard of mortality (HR, 0.86; 95% CI, 0.72-1.00), but this association attenuated with the addition of individual race/ethnicity (HR, 0.92; 95% CI, 0.78-1.09). In multivariable age-stratified analyses, those younger than 64 showed a lower hazard for mortality in the highest (vs. lowest) HED tertile (HR, 0.66; 95% CI, 0.49-0.90). Null associations were observed among patients ≥ 64 years. CONCLUSIONS: Treating in communities with greater HED and racial/ethnic integration was associated with lower mortality among younger patients which points to neighborhood context and social cohesion as potential drivers of improved survival outcomes for patients receiving hemodialysis.

BackgroundGingivitis is a non-specific inflammatory lesion in response to the accumulation of oral biofilm and is a necessary precursor to periodontitis. Enhanced oral hygiene practices, including utilization of a dentifrice that could significantly improve plaque accumulation and gingival inflammation, is desirable to prevent and treat gingivitis and potentially prevent progression to periodontitis. This clinical study aimed to investigate the effect of a new stannous fluoride-containing dentifrice with 2.6% ethylenediamine tetra acetic acid (EDTA) as an anti-tartar agent to reduce plaque index and gingival index over a 3-month study period compared to other commercially-available fluoride-containing dentifrices.MethodsThis double-blind, randomized controlled clinical study evaluated plaque, gingival inflammation, and sulcular bleeding in patients using one of five commercially available fluoride-containing dentifrices The dentifrices tested contained: 0.454% stannous fluoride and 2.6% EDTA (D1), 0.24% sodium fluoride (C), and 0.454% stannous fluoride (D2-D4). One hundred fifty subjects participated over a 3-month period. Co-primary endpoints were improvements in plaque index (PI) and modified gingival index (mGI) from baseline values. No professional cleaning was performed during the study period.ResultsAll subjects in the study demonstrated statistically significant improvements in all measures of oral hygiene over the 3-month study period. Subjects using dentifrice 1 (D1) showed statistically significantly greater reductions in PI, mGI, and modified sulcular bleeding index (mSBI) compared with all other commercially-available dentifrices tested (p

Objectives Methods Results Conclusion Clinical Significance To evaluate the color‐match with extracted natural teeth of three single‐shade universal composites, a group‐shade universal composite, and a highly translucent‐shade conventional composite.Twenty extracted human teeth were divided into light‐ and dark‐shade groups (n = 10, LSG and DSG). A preparation was restored with the 3 single‐shade universal composites, OMNICHROMA (OMC), Admira Fusion x‐tra U (AFU), and Essentia U (ESU); a highly translucent‐shade conventional composite, Tetric EvoCeram T (TEC‐T); and two shades of a group‐shade universal composite—Filtek Universal Restorative (FUR A1 and A4). Composites were photopolymerized, polished, and stored in water for 24 h. The ΔE00 value between the unprepared and restored surfaces was obtained using a spectrophotometer. Composite placement and measurements were repeated three times per tooth. Color differences were statistically analyzed with the within‐between‐subjects t‐test and repeated‐measures analysis of variance (ANOVA), followed by post hoc pairwise comparisons with a Bonferroni adjustment (α = 0.05).There were no statistically significant differences between OMC and FUR (A1 and A4). AFU and ESU showed significantly higher ΔE00 values than OMC and TEC‐T (p < 0.05). Single‐shade composites exhibited significantly higher ΔE00 values in the DSG than in the LSG except ESU (p < 0.05). None of the composites satisfied the criteria for an acceptable match (ΔE00 >1.8).OMC showed the same color matching ability as a group‐shade universal composite. A highly translucent‐shade conventional composite and OMC exhibited better color matching ability than other single‐shade composites. Overall, single‐shade universal composites performed better in lighter‐shaded teeth.Single‐shade universal composites have the potential to reduce chair time by eliminating shade selection in cavities with lighter‐shade teeth. Highly translucent incisal conventional composites also may be used if the appropriate shade of composite is not available. [ABSTRACT FROM AUTHOR]

Background: At present, combined provision of direct composite restorations and dental bleaching has become increasingly popular to meet the esthetic demands of patients. This study aimed to assess the effect of internal bleaching on microtensile bond strength of composite to freshly veneered enamel. Methods: In this in vitro experimental study, 50 sound extracted human premolars were randomly divided into five groups (n=10). All teeth received composite veneers. Two groups underwent no further intervention and were subjected to measurement of microtensile bond strength of composite to enamel 24 hr and one week after the veneering. The remaining three groups underwent internal bleaching. Group 3 underwent bleaching one month after the veneering, and microtensile bond strength was measured after 24 hr. In groups 4 and 5, bleaching was performed immediately after the veneering. Microtensile bond strength was measured after 24 hr in group 4 and after one month in group 5. Data were analyzed using one-way ANOVA. Results: All the groups were not significantly different regarding the mean bond strength (p=0.110), but they were significantly different in terms of the mode of failure (p=0.01) such that the mode of failure was mainly adhesive in the three bleached groups. Conclusion: Internal bleaching after composite veneering has no significant effect on microtensile bond strength of composite to the enamel. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing emphasis on exploring the influence of spirituality/religion on the management of mental health disorders. The aim of this study was to investigate the viewpoints of Iranian patients with mental health disorders regarding the incorporation of spirituality into their assessment. Methods: This cross-sectional study was conducted in 2021 at Iran University of Medical Sciences. Initially, a questionnaire was developed based on key spiritual concepts identified from a literature review. The content and face validity of the questionnaire were evaluated by an expert panel, and its reliability was assessed using Cronbach's alpha coefficient. Data collection was carried out in the second phase, with the questionnaire consisting of 4 questions examining the patients' perceived need and willingness for their therapist to explore their spiritual and religious dimensions. Data analysis was performed using appropriate statistical tests. Results: The questionnaire's validity was confirmed, and its reliability was demonstrated with a Cronbach's alpha value of 0.79. A total of 368 patients participated in the study. No significant associations were observed between the participants' educational level, diagnosis type, gender, and the questionnaire scores. Approximately half of the patients with mental health disorders expressed a desire to incorporate spiritual assessments into their psychological evaluations, with most welcoming this integration. Conclusion: The findings of this study suggest that despite challenges and barriers, efforts should be made to integrate spiritual dimensions into the treatment of patients. [ABSTRACT FROM AUTHOR]

Aim: The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults. Methods: This cross‐sectional study included 164 participants aged 35–80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables. Results: A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera. Conclusions: In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower‐extremity muscle function. Geriatr Gerontol Int 2024; 24: 53–60. [ABSTRACT FROM AUTHOR]

BackgroundAlterations in white matter microstructure associated with chronic alcohol use have been demonstrated in previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether such differences are influenced by an individual's biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls.MethodsOne hundred participants with AUD (38 female, aged 21 to 68) participating in the National Institute on Alcohol Abuse and Alcoholism's inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion-weighted scan. Images collected were processed for each subject individually, and voxelwise, tract-based spatial statistics analysis was conducted to test for differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD).ResultsA 2-way, between-subjects ANCOVA that tested for differences by group and sex revealed widespread differences between AUD and control subjects, but no interaction between group and sex. Additional analyses exploring demographic and alcohol use variables showed significant impacts of age on white matter microstructure that were more pronounced in individuals with AUD. Plots of FA by age, sex, and group in major white matter tracts suggest a need to explore higher order interactions in larger samples.ConclusionsThese results bolster recent findings of similar microstructural properties in men and women with AUD but provide a rationale for the consideration of age when investigating the impacts of chronic alcohol use on the brain's white matter.

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BackgroundThe link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP).MethodsWe included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese

BackgroundMajor cancer organizations recommend depression screening in patients and survivors. The 9-item Patient Health Questionnaire (PHQ-9) is often suggested, with limited information about its use.MethodsEnrollment data collected from younger breast cancer survivors participating in a behavioral intervention trial were used to examine the relationship between PHQ-9 scores (range = 0-27), patient characteristics, and responses to standardized psychosocial assessment tools. Major depressive disorder criterion was met if responses to the first 2 PHQ-9 items (range = 0-6) were 3 or greater. The sample was categorized by total PHQ-9 scores: less than 5 (minimal depressive symptoms), 5-9 (mild to moderate depressive symptoms), and 10 or greater (moderate to severe depression). PHQ-9 category associations with medical, demographic, psychosocial, and behavioral characteristics were examined using analysis of variance for continuous variables and χ2 tests for categorical variables.ResultsA total of 231 women met the study prescreening eligibility criterion of mild depressive symptoms and enrolled in the study. On average, they were 45.2 years old and 2.6 years since diagnosis. At enrollment, 22.1% met the screening criterion for possible major depressive disorder; among those with PHQ-9 scores of 10 or greater, 58.3% met this criterion. Anxiety, fatigue, insomnia, and intrusive thoughts about cancer were frequent and were associated with depressive symptom severity (all P < .001). In contrast, neither demographic nor cancer treatment characteristics were associated with depressive symptoms.ConclusionsDepressive symptoms in this selected sample of younger breast cancer survivors were independent of demographic characteristics or cancer treatment history, suggesting that depression screening is necessary to detect uncontrolled depressive symptoms.

Thermal adaptation to habitat variability can determine species vulnerability to environmental change. For example, physiological tolerance to naturally low thermal variation in tropical forests species may alter their vulnerability to climate change impacts, compared with open habitat species. However, the extent to which habitat-specific differences in tolerance derive from within-generation versus across-generation ecological or evolutionary processes are not well characterized. Here we studied thermal tolerance limits of a Central African butterfly (Bicyclus dorothea) across two habitats in Cameroon: a thermally stable tropical forest and the more variable ecotone between rainforest and savanna. Second generation individuals originating from the ecotone, reared under conditions common to both populations, exhibited higher upper thermal limits (CTmax) than individuals originating from forest (∼3°C greater). Lower thermal limits (CTmin) were also slightly lower for the ecotone populations (∼1°C). Our results are suggestive of local adaptation driving habitat-specific differences in thermal tolerance (especially CTmax) that hold across generations. Such habitat-specific thermal limits may be widespread for tropical ectotherms and could affect species vulnerability to environmental change. However, microclimate and within-generation developmental processes (e.g. plasticity) will mediate these differences, and determining the fitness consequences of thermal variation for ecotone and rainforest species will require continued study of both within-generation and across-generation eco-evolutionary processes.This article has an associated First Person interview with the first author of the paper.

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much-needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.

Dietary behavior change is difficult to accurately measure in a low-income youth population. Objective tools to measure fruit and vegetable consumption without relying on self-report present the opportunity to do this with less respondent burden and bias. A promising tool for quantifying fruit and vegetable consumption via proxy is skin carotenoids as measured by reflection spectroscopy through a device called the Veggie Meter®. To assess whether the Veggie Meter® is able to detect changes in skin carotenoids as a proxy for fruit and vegetable consumption in a low-income school setting, skin carotenoid measurements were collected at three time points, along with student level demographics, anthropometric measurements, and nutrition knowledge. A secondary goal of this study was to refine the protocol to be used based on researcher observations. Repeated measures analysis of variance with Bonferroni correction for multiple comparisons indicate that there was a significant difference in VM scores over the course of the study (F(2, 68) = 6.63, p = 0.002), with an increase in skin carotenoids from Fall 2018 to Spring 2019 (p = 0.005). This increase was sustained over the summer months when measured in Fall 2019. Changes to the protocol included the addition of a hand cleaning step and using the non-dominant ring finger for data collection. With these refinements, the results demonstrate that the Veggie Meter® is usable as a non-invasive tool for measuring fruit and vegetable consumption in a population that is traditionally difficult to assess.

Despite widespread interest in variance in affect, basic questions remain pertaining to the relative proportions of between-person and within-person variance, the contribution of days and moments, and the reliability of these estimates. We addressed these questions by decomposing negative affect and positive affect variance across three levels (person, day, moment), and calculating reliability using a coordinated analysis of seven daily diary, ecological momentary assessment (EMA), and diary-EMA hybrid studies (across studies age = 18-84 years, total Npersons = 2,103, total Nobservations = 45,065). Across studies, within-person variance was sizeable (negative affect: 45% to 66%, positive affect: 25% to 74%); in EMA more within-person variance was attributable to momentary rather than daily level. Reliability was adequate to high at all levels of analysis (within-person: .73-.91; between-person: .96-1.00) despite different items and designs. We discuss the implications of these results for the design of future intensive studies of affect variance.

BackgroundChronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated.MethodsThe study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks.DiscussionThis study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables.Trial registrationClinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

Despite widespread interest in variance in affect, basic questions remain pertaining to the relative proportions of between-person and within-person variance, the contribution of days and moments, and the reliability of these estimates. We addressed these questions by decomposing negative affect and positive affect variance across three levels (person, day, moment), and calculating reliability using a coordinated analysis of seven daily diary, ecological momentary assessment (EMA), and diary-EMA hybrid studies (across studies age = 18-84 years, total Npersons = 2,103, total Nobservations = 45,065). Across studies, within-person variance was sizeable (negative affect: 45% to 66%, positive affect: 25% to 74%); in EMA more within-person variance was attributable to momentary rather than daily level. Reliability was adequate to high at all levels of analysis (within-person: .73-.91; between-person: .96-1.00) despite different items and designs. We discuss the implications of these results for the design of future intensive studies of affect variance.

Background: This study investigated the efficacy of electrical nerve stimulation for neuromuscular and functional performance recovery after acute traumatic spinal cord injury (TSCI). Methods: Twenty-nine participants with TSCI (20 males and 9 females) were randomly assigned to study group (SG) and control group (CG). Treatment started within 24 h of injury at 3 days/week for 24 weeks. Both groups were treated with a functional re-education approach while SG had electrical nerve stimulation in addition. The American Spinal Cord Injury Association (ASIA) scale was used to assess the severity of TSCI, the Spinal Cord Independence Measure evaluated functional performance, Neuromuscular Recovery Scale measured neuromuscular recovery, Walking Index assessed walking function, and a tape rule was used to measure participants' girth. Measurements were taken at baseline and every 6 weeks thereafter. Data were analyzed using the Friedman Analysis of Variance, the Wilcoxon–rank test, and Independent t-test. Results: Participants were aged 15–58 years (mean = 36.75 ± 11.75 and median = 37 years), with 19 (65.5%) within 19–40 years' range. Eighteen (62.1%) had cervical, three (10.2%) thoracic, and eight (27.5%) had lumbar TSCI. Nine (31.0%) each presented with ASIA-A and ASIA-C, seven (24.1%) ASIA-B, and four (13.9%) ASIA-D. Consistent significant (P < 0.05) improvement in neuromuscular and functional performance recovery within SG as compared with CG was recorded, with improvements across the five points of measurement. Walking function improved clinically in SG and no muscle atrophy was recorded throughout 24 weeks. The level of statistical significance was set at P < 0.05. Conclusion: Electrical nerve stimulation combined with early functional re-training effectively improves neuromuscular and functional performance recovery in acute TSCI. [ABSTRACT FROM AUTHOR]

Quality of care is essential for improving health outcomes, but heterogeneity in theoretical frameworks and metrics can limit studies' generalizability and comparability. This research aimed to compare definitions of care quality across research articles that incorporate data from Service Provision Assessment (SPA) surveys. Following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we used a keyword search in PubMed. Each author reviewed abstracts, then full texts, for inclusion criteria, and peer-reviewed publications of empirical analysis using SPA data. The search yielded 3,250 unique abstracts, and 34 publications were included in the final analysis. We extracted details on the SPA dataset(s) used, theoretical framework applied, and how care quality was operationalized. The 34 included articles used SPA data from 14 surveys in nine countries (all in sub-Saharan Africa plus Haiti). One-third of these articles (n = 13) included no theoretical or conceptual framework for care quality. Among those articles referencing a framework, the most common was the Donabedian model (n = 7). Studies operationalized quality constructs in extremely different ways. Few articles included outcomes as a quality construct, and the operationalization of structure varied widely. A key asset of SPA surveys, owing to the standardized structure and use of harmonized data collection instruments, is the potential for cross-survey comparisons. However, this is limited by the lack of a common framework for measuring and reporting quality in the existing literature using SPA data. Service Provision Assessment surveys offer unique and valuable insights, and a common framework and approach would substantially strengthen the body of knowledge on quality of care in low-resource settings.

BackgroundJohns Hopkins was an early adopter of an in-house nephrology fellowship night float to improve work-life balance. Our study aimed to elucidate attitudes to guide fellowship structuring.MethodsWe performed a mixed-methods study surveying Johns Hopkins fellows, alumni, and faculty and conducting one focus group of current fellows. Surveys were developed through literature review, queried on a five-point Likert scale, and analyzed with t and ANOVA tests. The focus group transcript was analyzed by two independent reviewers.ResultsSurvey response rates were 14 (100%) fellows, 32 (91%) alumni, and 17 (94%) faculty. All groups felt quality of patient care was good to excellent with no significant differences among groups (range of means [SD], 4.1 [0.7]-4.6 [0.7]; P=0.12), although fellows had a statistically significantly more positive view than faculty on autonomy (4.6 [0.5] versus 4.1 [0.3]; P=0.006). Fellows perceived a positive effect across all domains of night float on the day team experience (range, 4.2 [0.8]-4.6 [0.6]; P

BackgroundMedication adherence is a critical issue in achieving viral suppression targets, particularly in resource-limited countries. As HIV-related cognitive impairment (CI) impacts adherence, we examined frequency and predictors of CI in the African Cohort Study.SettingCross-sectional examination of enrollment data from President's Emergency Plan for AIDS Relief supported clinic sites.MethodsIn a 30-minute cognitive assessment, CI was defined as -1SD on 2 tests or -2SD on one, as compared with 429 controls. We performed univariable and multivariable logistic and linear models examining clinical and demographic factors associated with CI and global neuropsychological performance (NP-6).ResultsTwo thousand four hundred seventy-two HIV+ participants from Kenya (n = 1503), Tanzania (n = 469), and Uganda (n = 500). The mean (SD) age was 39.7 (10.7) years, and 1452 (59%) were women. The majority reported completing or partially completing primary school (n = 1584, 64%). Mean (SD) current and nadir CD4 count were 463 (249) and 204 (221) cells/mm, respectively; 1689 (68%) were on combination antiretroviral therapy. Nine hundred thirty-nine (38%) HIV+ versus 113 (26%) HIV- individuals showed CI: (P < 0.001). We found significant effects of literacy [odds ratio (OR): 0.3; 95% CI: 0.2 to 0.4; P < 0.001] and World Health Organization stage 4 (OR: 1.5; 95% CI: 1.0 to 2.q; P = 0.046) on CI. Tanzanians (OR: 3.2; 95% CI: 2.4 to 4.3; P < 0.001) and Kenyans (OR: 2.0; 95% CI: 1.6 to 2.6; P < 0.001) had higher risk of CI compared with Ugandans. Results were relatively unchanged in predictive models of NP-6, with the only difference being an additional significant effect of current CD4 cell count (coeff: 0.0; 95% CI: 0.0 to 0.0; P = 0.005).ConclusionsLiteracy, country, World Health Organization stage, and current CD4 cell count were associated with increased risk of cognitive dysfunction. Our findings help optimize care practices in Africa, illustrating the importance of strategies for early and effective viral-immunological control.

ObjectiveTo identify current maternal and infant predictors of infant mortality, including maternal sociodemographic and economic status, maternal perinatal smoking and obesity, mode of delivery, and infant birthweight and gestational age.MethodsThis retrospective study analyzed data from the linked birth and infant death files (birth cohort) and live births from the Birth Statistical Master files (BSMF) in California compiled by the California Department of Public Health for 2007-2015. The birth cohort study comprised 4,503,197 singleton births including 19,301 infant deaths during the nine-year study period. A subpopulation to study fetal growth consisted of 4,448,300 birth cohort records including 13,891 infant deaths.ResultsThe infant mortality rate (IMR) for singleton births decreased linearly (p

BackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value

A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with the Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimens included human plasma and serum from male and female donors, mouse and rat plasma, as well as NIST SRM 1950 reference plasma. The metabolite classes covered range from polar (e.g., amino acids and biogenic amines) to nonpolar (e.g., diacyl- and triacyl-glycerols), and they span 11 common metabolite classes. The manuscript describes a strict system suitability testing (SST) criteria used to evaluate each laboratory's readiness to perform the assay, and provides the SST Skyline documents for public dissemination. The study found approximately 250 metabolites were routinely quantified in the sample types tested, using Orbitrap instruments. Interlaboratory variance for the NIST SRM-1950 has a median of 10% for amino acids, 24% for biogenic amines, 38% for acylcarnitines, 25% for glycerolipids, 23% for glycerophospholipids, 16% for cholesteryl esters, 15% for sphingolipids, and 9% for hexoses. Comparing to consensus values for NIST SRM-1950, nearly 80% of comparable analytes demonstrated bias of

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

Background and Objectives: The objective of this experiment was to evaluate the effects of acute exercise on memory interference and determine if this potential relationship is moderated by sex. Materials and Methods: A randomized controlled experiment was conducted (N = 40), involving young adult males (n = 20) and females (n = 20) completing two counterbalanced visits (exercise and no exercise). The exercise visit involved an acute (15 min), moderate-intensity bout of treadmill exercise, while the control visit involved a time-matched seated task. Memory interference, including both proactive interference and retroactive interference, involved the completion of a multi-trial memory task. Results: In a factorial ANOVA with the outcome being List B, there was a main effect for condition (F(1,38) = 5.75, P = 0.02, n2p = 0.13), but there was no main effect for sex (F(1,38) = 1.39, P = 0.24, n2p = 0.04) or sex by condition interaction (F(1,38) = 1.44, P = 0.23, n2p = 0.04). Conclusion: In conclusion, acute moderate-intensity exercise was effective in attenuating a proactive memory interference effect. This effect was not moderated by biological sex.

The use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, with a variety of e-liquids/e-juices, is increasing at an alarming rate among adolescents who do not realize the potential harmful health effects. This study examines the harmful effects of ENDS on the liver. Apolipoprotein E null (ApoE-/-) mice on a western diet (WD) were exposed to saline or ENDS with 2.4% nicotine aerosol for 12 weeks using our mouse ENDS exposure model system, which delivers nicotine to mice and leads to equivalent serum cotinine levels found in human cigarette users. ApoE-/- mice on a WD exposed to ENDS exhibited a marked increase in hepatic lipid accumulation compared with ApoE-/- on a similar diet exposed to saline aerosol. The detrimental effects of ENDS on hepatic steatosis were associated with significantly greater oxidative stress, increased hepatic triglyceride levels, and increased hepatocyte apoptosis, independent of adenosine monophosphate-activated protein kinase signaling. In addition, hepatic RNA sequencing analysis revealed that 433 genes were differentially expressed in ENDS-exposed mice on WD compared with saline-exposed mice. Functional analysis indicates that genes associated with lipid metabolism, cholesterol biosynthesis, and circadian rhythm were most significantly altered in the liver in response to ENDS. Conclusion: These results demonstrate profound adverse effects of ENDS on the liver. This is important information for regulatory agencies as they regulate ENDS.

BACKGROUND:Platelet (Plt) derived-extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular endothelial cell permeability, similar to fresh Plts. To investigate this hypothesis we utilized in vitro and in vivo models of vascular endothelial compromise and bleeding. METHODS:In vitro: Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution. Effects of Plts and Plt-EVs on endothelial barrier function was assessed by trans - endothelial electrical resistance (TEER) measurements and histological analysis of endothelial junction proteins. Hemostatic potential of Plt-EVs and Plts were assessed by multiple electrode Plt aggregometry. In vivo: The effects of Plts and Plt-EVs on vascular permeability and bleeding were assessed in NOD-SCID mice by an established Miles Assay of vascular permeability and a tail snip bleeding assay. RESULTS:In vitro: Plt-EVs displayed exosomal size distribution and expressed Plt specific surface markers. Plts and Plt-EVs decreased EC permeability and restored EC junctions after thrombin challenge. Multiplate aggregometry revealed that Plt-EVs enhanced Thrombin Receptor Activating Peptide (TRAP) mediated aggregation of whole blood, whereas Plts enhanced TRAP, Arachidonic Acid (ASPI), Collagen, and Adenosine Diphosphate (ADP) mediated aggregation. In vivo: Plt-EVs are equivalent to Plts in attenuating VEGF-A induced vascular permeability and uncontrolled blood loss in a tail snip hemorrhage model. CONCLUSION:Our study is the first to report that Plt-EVs might provide a feasible product for transfusion in trauma patients to attenuate bleeding, inhibit vascular permeability and mitigate the endotheliopathy of trauma (EOT). STUDY TYPE:Original Article LEVEL OF EVIDENCE: This is a pre-clinical study so it does not confirm to the level of evidence table for all clinical studies and case reports.

The ventilator-associated event (VAE) is a potentially avoidable complication of mechanical ventilation (MV) associated with poor outcomes. Although rare, VAEs and other nosocomial events are frequently targeted for quality improvement efforts consistent with the creed to 'do no harm'. In October 2016, VA Greater Los Angeles (GLA) was in the lowest-performing decile of VA medical centres on a composite measure of quality, owing to GLA's relatively high VAE rate. To decrease VAEs, we sought to reduce average MV duration of patients with acute respiratory failure to less than 3 days by 1 July 2017. In our first intervention (period 1), intensive care unit (ICU) attending physicians trained residents to use an existing ventilator bundle order set; in our second intervention (period 2), we updated the order set to streamline order entry and incorporate new nurse-driven and respiratory therapist (RT)-driven spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT) protocols. In period 1, the proportion of eligible patients with SAT and SBT orders increased from 29.9% and 51.2% to 67.4% and 72.6%, respectively, with sustained improvements through December 2017. Mean MV duration decreased from 7.2 days at baseline to 5.5 days in period 1 and 4.7 days in period 2; statistical process control charts revealed no significant differences, but the difference between baseline and period 2 MV duration was statistically significant at p=0.049. Bedside audits showed RTs consistently performed indicated SBTs, but there were missed opportunities for SATs due to ICU staff concerns about the SAT protocol. The rarity of VAEs, small population of ventilated patients and infrequent use of sedative infusions at GLA may have decreased the opportunity to achieve staff acceptance and use of the SAT protocol. Quality improvement teams should consider frequency of targeted outcomes when planning interventions; rare events pose challenges in implementation and evaluation of change.

Is there a fixed limit on how many objects we can hold actively in mind? Generally, researchers have found participants are worse at remembering a small number of objects if those objects are more complex, suggesting a limited resource rather than a fixed number of objects best explains working memory performance. However, some evidence has suggested that stimulus similarity better accounts for these effects and that, after accounting for such similarity, the data support a slot-based fixed item limit for working memory. Much of the evidence used to support the latter claim relies on working memory displays containing different categories of items. It has been found that, for large, across-category changes, performance does not differ for different kinds of complex stimuli. However, many of these studies fail to adequately control for the potential use of ensemble information in discriminating such large changes. Here, we sought to identify how much ensemble representations may explain performance across these tasks. In Experiment 1, we observed that, as set size increased from four to 12 items, capacity estimates for across-category changes increased linearly as well, providing evidence against the claim of a fixed capacity. In Experiment 2, we controlled for stimulus complexity and similarity but varied the utility of ensemble representations for the change-detection task. We observed significantly greater capacity when ensemble information could be used. Altogether, these results are contrary to a slot-like, fixed-object constraint on working memory capacity and consistent with object complexity and ensemble representations strongly affecting working memory performance.

BackgroundDespite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery.MethodsParticipants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently.ResultsOf 3,105 participants, 1,921 (62%) underwent catheterization and 1,184 (38%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95% confidence interval: -0.046 to 0.005 memory units, p = 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26% or 0.19% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95% confidence interval: 0.74 to 1.18).ConclusionsIn this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.

ObjectiveTo identify correlates of HIV/STI prevalence among 13 cities with varying sizes of female sex worker (FSW) populations and municipal characteristics in Mexico.Materials and methodsFSWs underwent interviews and testing for HIV, syphilis, gonorrhea and chlamydia. Logistic regression explored variations in HIV/STI prevalence.ResultsAmong FSWs (n=1 092), prevalence across 13 sites was: HIV: 0.4% (range: 0%-1.4%): syphilis: 7.8% (range: 0%-17.2%); chlamydia: 15.3% (range: 5.7%-32.2%); gonorrhea:2.9% (range 0%-13.8%), and any HIV/STI: 23% (range: 9.9%- 46%). Municipalities with high human development scores and a lower municipal marginalization index had higher odds of combined HIV/STI prevalence. After controlling for sitespecific variability in municipal characteristics, greater risk of HIV/STIs was associated with lower education, having a spouse diagnosed or treated for an STI, unaffordability of condoms, and having non-Mexican clients.ConclusionsPrevalence of HIV/STIs varies across Mexican municipalities indicating the need for surveillance to identify hotspots for targeted resource allocation.

We investigated whether a mindfulness meditation program delivered via a smartphone application could improve psychological well-being, reduce job strain, and reduce ambulatory blood pressure during the workday. Participants were 238 healthy employees from two large United Kingdom companies that were randomized to a mindfulness meditation practice app or a wait-list control condition. The app offered 45 prerecorded 10- to 20-min guided audio meditations. Participants were asked to complete one meditation per day. Psychosocial measures and blood pressure throughout one working day were measured at baseline and eight weeks later; a follow-up survey was also emailed to participants 16 weeks after the intervention start. Usage data showed that during the 8-week intervention period, participants randomized to the intervention completed an average of 17 meditation sessions (range 0-45 sessions). The intervention group reported significant improvement in well-being, distress, job strain, and perceptions of workplace social support compared to the control group. In addition, the intervention group had a marginally significant decrease in self-measured workday systolic blood pressure from pre- to post-intervention. Sustained positive effects in the intervention group were found for well-being and job strain at the 16-week follow-up assessment. This trial suggests that short guided mindfulness meditations delivered via smartphone and practiced multiple times per week can improve outcomes related to work stress and well-being, with potentially lasting effects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Visual working memory is the mechanism supporting the continued maintenance of information after sensory inputs are removed. Although the capacity of visual working memory is limited, memoranda that are spaced farther apart on a 2-D display are easier to remember, potentially because neural representations are more distinct within retinotopically organized areas of visual cortex during memory encoding, maintenance, or retrieval. The impact on memory of spatial separability in depth is less clear, even though depth information is essential to guiding interactions with objects in the environment. On one account, separating memoranda in depth may facilitate performance if interference between items is reduced. However, depth information must be inferred indirectly from the 2-D retinal image, and less is known about how visual cortex represents depth. Thus, an alternative possibility is that separation in depth does not attenuate between-items interference; it may even impair performance, as attention must be distributed across a larger volume of 3-D space. We tested these alternatives using a stereo display while participants remembered the colors of stimuli presented either near or far in the 2-D plane or in depth. Increasing separation in-plane and in depth both enhanced performance. Furthermore, participants who were better able to utilize stereo depth cues showed larger benefits when memoranda were separated in depth, particularly for large memory arrays. The observation that spatial separation in the inferred 3-D structure of the environment improves memory performance, as is the case in 2-D environments, suggests that separating memoranda in depth might reduce neural competition by utilizing cortically separable resources.

INTRODUCTION: Noncompaction cardiomyopathy (NCCM) patients may develop sustained ventricular arrhythmias (VA). Currently no known electrocardiogram (ECG) parameter has demonstrated predictive value for VA development. The spatial QRS-T angle has demonstrated ability to identify VA in other cardiomyopathy populations. METHODS: A total of 39 patients with NCCM, defined by compact to non-compact ratio of >2.3 by magnetic resonance imaging, were assessed. The first ECG taken at time of MRI was assessed utilizing the heart rate, the QRS duration (QRSd), the corrected QT interval (QTc), and the spatial QRS-T angle (SPQRS-T angle, three-dimensional angle between the QRS and T-wave vectors) were assessed. RESULTS: Eight patients developed VA (20.5%). Median time to event was 3 months (95% CI 1.0 to 24.0 months). There were no significant differences between baseline ejection fraction or fractional shortening. Baseline median heart rate, spatial QRS-T angles, and indexed left ventricular end-diastolic volumes were all significantly higher in patients with VA development (p-value

PurposeTo study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels.MethodsA subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t-test.ResultsThe 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508).ConclusionsIn this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects.

PurposeTo investigate conjunctival and intrascleral vasculatures using anterior segment optical coherence tomography angiography (AS-OCTA) in normal eyes.DesignCross-sectional study.MethodsAS-OCTA images of the corneal limbus were acquired circumferentially using a swept-source optical coherence tomography system in 10 eyes of 10 healthy subjects. AS-OCTA flow patterns with en face maximum projection were compared between the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 μm to 1000 μm) layers. The OCTA images were also compared with fluorescein scleral angiography and indocyanine green aqueous angiography images. Quantitative parameters (vessel density, vessel length density, vessel diameter index, and fractal dimension) were compared among different locations.ResultsThe OCTA vessel patterns differed between the superficial and deep layers. The superficial-layer flow signals showed centrifugal patterns from the limbus, whereas the deep-layer flow signals showed segmental patterns. The OCTA en face images with whole signals had a similar appearance to the scleral angiography images, whereas those in the deep layer showed a similar appearance to the aqueous angiography images. In the superficial layer, only the vessel diameter index was significantly different among the locations (P = .003). In the deep layer, all 4 parameters differed significantly among the locations (P < .001 to P = .003).ConclusionsOCTA is a promising tool for evaluating conjunctival and intrascleral vasculatures. It may also help in understanding ocular surface blood flow relevant to vascular and ocular surface diseases, as well as aqueous humor outflow.

PurposeTo compare race-related differences in estimated rate of change of Bruch's membrane opening-minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer thickness (RNFLT) in healthy, glaucoma suspect, and glaucoma eyes of individuals of European (ED) and African descent (AD).DesignProspective cohort study.MethodsThis study investigated rate of change of BMO-MRW and RNFLT in 124 healthy, 227 glaucoma suspect, and 177 glaucoma eyes followed for approximately 3 years and tested with optical coherence tomography every 6 months. Suspect eyes had a history of untreated intraocular pressure (IOP) ≥ 22 mm Hg or suspicion of glaucoma by optic disc photograph assessment without repeatable abnormal standard automated perimetry (SAP) results. Glaucoma eyes had repeatable abnormal SAP results (GHT ONL or PSD ≤ 5%). Mixed-effects models were used to estimate the rate of change after controlling for age, mean follow-up IOP, central corneal thickness, axial length, and BMO area.ResultsA race-related difference in rate of change of global BMO-MRW but not average RNFLT in suspect eyes was observed. Rate of change of BMO-MRW was -1.82 μm/year and -2.20 μm/year in ED and AD suspect eyes, respectively (P = .03). Rate of change of RNFLT was -0.64 μm/year and -0.75 μm/year in ED and AD suspect eyes, respectively (P = .75). No race-related differences in change rate were found in healthy or glaucoma eyes.ConclusionRace is an important consideration when assessing structural change, particularly minimum rim width, in glaucoma suspect eyes. Differences in rate of structural change may help explain racial disparities in glaucoma susceptibility.

ObjectiveThe aim of the study was to examine whether anxiety and depressive symptoms are associated with an adverse cardiac autonomic profile among midlife women with hot flashes.MethodsAnxiety and depressive symptoms were evaluated by validated self-administered questionnaires among peri- and postmenopausal women in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, and respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, were measured at baseline and 12 weeks using impedance cardiography and electocardiography. Multivariable repeated measures linear regression models examined associations between anxiety and depression symptoms and autonomic markers, corrected for multiple comparisons with Benjamini-Hochberg procedure, and adjusted for age and body mass index.ResultsAmong the 121 participants, greater state anxiety was associated with shorter PEP, reflecting higher sympathetic activity (β = -0.24, P = 0.02). Greater trait anxiety and cognitive anxiety were associated with lower RSA, reflecting decreased parasympathetic activity (β = -0.03, P

ObjectivesTo assess inter-sonographer reproducibility of ultrasound attenuation coefficient (AC), backscatter coefficient (BSC) and shear wave speed (SWS) in adults with known/suspected non-alcoholic fatty liver disease (NAFLD).MethodsThe institutional review board approved this HIPAA-compliant prospective study; informed consent was obtained. Participants with known/suspected NAFLD were recruited and underwent same-day liver examinations with a clinical scanner. Each participant was scanned by two of the six trained sonographers. Each sonographer performed multiple data acquisitions in the right liver lobe using a lateral intercostal approach. A data acquisition was a single operator button press that recorded a B-mode image, radio-frequency data, and the SWS value. AC and BSC were calculated from the radio-frequency data using the reference phantom method. SWS was calculated automatically using product software. Intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wCV) were calculated for applicable metrics.ResultsSixty-one participants were recruited. Inter-sonographer ICC was 0.86 (95% confidence interval: 0.77-0.92) for AC and 0.87 (0.78-0.92) for log-transformed BSC (logBSC = 10log10BSC) using one acquisition per sonographer. ICC was 0.88 (0.80-0.93) for both AC and logBSC averaging 5 acquisitions. ICC for SWS was 0.57 (0.29-0.74) using one acquisition per sonographer, and 0.84 (0.66-0.93) using 10 acquisitions. The wCV was ~7% for AC, and 19-43% for SWS, depending on number of acquisitions.ConclusionsHepatic AC, BSC and SWS measures on a clinical scanner have good inter-sonographer reproducibility in adults with known or suspected NAFLD. Multiple acquisitions are required for SWS but not AC or BSC to achieve good inter-sonographer reproducibility.Key points• AC, BSC and SWS measurements are reproducible in adults with NAFLD. • Inter-sonographer reproducibility of SWS measurement improves with more acquisitions being averaged. • Multiple acquisitions are required for SWS but not AC or BSC.

ObjectiveThe aim of the study was to examine whether anxiety and depressive symptoms are associated with an adverse cardiac autonomic profile among midlife women with hot flashes.MethodsAnxiety and depressive symptoms were evaluated by validated self-administered questionnaires among peri- and postmenopausal women in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, and respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, were measured at baseline and 12 weeks using impedance cardiography and electocardiography. Multivariable repeated measures linear regression models examined associations between anxiety and depression symptoms and autonomic markers, corrected for multiple comparisons with Benjamini-Hochberg procedure, and adjusted for age and body mass index.ResultsAmong the 121 participants, greater state anxiety was associated with shorter PEP, reflecting higher sympathetic activity (β = -0.24, P = 0.02). Greater trait anxiety and cognitive anxiety were associated with lower RSA, reflecting decreased parasympathetic activity (β = -0.03, P

Background: Countries around the world are now racing to vaccinate people against SARS-CoV-2, the virus that causes COVID-19.The Government of India also rolled out its vaccination drive from 16th January '2021. Aims: To estimate the antibody response of the COVID-19 vaccine in the form of SARS-COV-2 IgG antibodies in vaccinated healthcare workers. Methods: Prospective follow-up was study conducted on healthcare workers (HCWs) of a Medical college in Dehradun, Uttarakhand. Healthcare workers who have been vaccinated for COVID-19 were tested for SARS-CoV-2-IgG antibodies at regular intervals i.e at 4 weeks after the 1st dose and then again at 4 weeks after the 2nd dose. The third sample was taken 6 months after the 2nd dose. Results: A total of 302 HCWs were enrolled in the study who gave their samples for IgG antibody estimation after the covishield vaccine. After 4 weeks of completion of both doses, 96% HCWs formed SARS-COV-2 IgG antibodies, whereas 4% didn't. Then after 6 months of follow-up, 14% HCWs have become negative for antibodies and better immunity is seen in people who also got infected with COVID-19 during this time. Conclusion: This study concludes that the immunity gained after vaccination is waning off in around 6 months and there is a need for a booster dose, especially for people at high risk. The infection control practices still play a crucial role in the prevention of this deadly disease. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a significant public problem and the third cause of cancer-induced death all over the world. Long noncoding RNA (lncRNA) has been reported as a vital mediator in human cancer. However, the precise role of lncRNA myocardial infarction associated transcript (MIAT) in CRC is unclear. Materials and Methods: The abundance of MIAT, miR-488-3p, and the type 1 insulin-like growth factor receptor (IGF1R) was measured by real-time quantitative polymerase chain reaction assay. Western blot assay was carried out to assess the protein level in CRC samples or control group. The cell activity, abilities of migration and invasion, and glycolysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and testing glucose consumption and lactate product, correspondingly. The target association between miR-488-3p, MIAT, or IGF1R was predicted and established by bioinformatics tools, dual-luciferase reporter, and RNA pull-down assays, correspondingly. The effects of MIAT silencing in vivo were analyzed by animal experiments. Results: LncRNA MIAT was upregulated in CRC sample and that was positively correlated with IGF1R expression. Loss-of-functional assay suggested that knockdown of MIAT impeded cell activity, migration, invasion, and glycolysis of CRC cells in vivo, along with xenograft growth in vivo. Moreover, silencing of IGF1R inhibited the progression of CRC. Therefore, overexpression of IGF1R could abolish silencing of MIAT-induced effects on CRC cells. Mechanistically, MIAT was a sponge for miR-488-3p, thereby regulating IGF1R expression in CRC. Conclusion: The present study confirmed that the "MIAT/miR-488-3p/IGF1R" pathway was involved in the development of CRC, which may be the target for developing therapeutic approaches for CRC. [ABSTRACT FROM AUTHOR]

Dermascopes are commonly utilized for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies have been used to aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermascope that enables real-time blood flow measurements of skin during conventional visual inspection. In-vitro characterization demonstrated that the dermascope is capable of quantifying changes in flow across a physiologically relevant range even when used in a handheld manner with clinic lighting and dermascope LEDs on. In a small pilot clinical study, we demonstrated the dermascope's ability to detect flow differences between two distinct lesion types.

ObjectiveTo evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multiracial/ethnic cohort of community-dwelling women.MethodsWe analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996-2013) from 2,435 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used discrete-time Cox proportional-hazards regression to identify predictors of incident vaginal dryness and to evaluate vaginal dryness as a predictor of pain during intercourse and changes in sexual intercourse frequency.ResultsThe prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42-53 years) to 34.0% at the 13th visit (ages 57-69 years). Advancing menopausal stage, surgical menopause, anxiety, and being married were positively associated with developing vaginal dryness, regardless of partnered sexual activity. For women not using hormone therapy, higher concurrent levels of endogenous estradiol were inversely associated (multivariable-adjusted hazard ratio: 0.94 per 0.5 standard deviation increase, 95% confidence interval: 0.91-0.98). Concurrent testosterone levels, concurrent dehydroepiandrosterone sulfate levels, and longitudinal change in any reproductive hormone were not associated with developing vaginal dryness. Both vaginal dryness and lubricant use were associated with subsequent reporting of pain during intercourse, but not with a decline in intercourse frequency.ConclusionIn these longitudinal analyses, our data support many clinical observations about the relationship between vaginal dryness, menopause, and pain during intercourse, and suggest that reporting of vaginal dryness is not related to androgen level or sexual intercourse frequency.

ObjectiveWe conducted a gene-environment interaction study to evaluate whether the association of body mass index (BMI) associated meta genome-wide association study single-nucleotide polymorphisms (SNPs) (as a genetic risk score) and BMI is modified by physical activity and age.MethodsIn 8,206 women of European ancestry from the Women's Health Initiative (WHI), we used linear regression to examine main effects of the 95 SNP BMI genetic risk score (GRS) and physical activity on BMI, and evaluated whether genetic associations are modified by physical activity (two-way interaction) and age (three-way interaction).ResultsWe found evidence for modification of the BMI GRS-BMI association according to both physical activity and age. We observed a significant two-way interaction of BMI GRS × physical activity in the crude model (P interaction = 0.05), where a smaller effect of the BMI GRS on BMI with increasing physical activity. The beta coefficient was 0.05 (standard error [SE] = 0.02, P = 0.01) for the high-activity group compared with beta = 0.13 (SE = 0.02, P = 4.8 × 10) for the sedentary group. The three-way interaction was statistically significant (adjusted P interaction = 0.01). Notably, in the 70+ age group, the BMI GRS-BMI association was attenuated and no longer significant in the high-activity group; the beta coefficient for the 70+ high-activity group was relatively small and nonsignificant (beta = 0.02, SE = 0.03, P = 0.58) compared with 70+ sedentary group (beta = 0.17, SE = 0.03, P = 2.5 × 10).ConclusionOur study suggests that physical activity attenuates the influence of genetic predisposition to obesity, and this effect is more profound in the oldest age group.

PurposeWhile meibography has proven useful in identifying structural changes in the meibomian gland (MG), little is known regarding the MG spectral transmission and absorption characteristics. The purpose of this study was to measure the transmission/absorption spectra of the MG compared to other eyelid tissues.MethodsHuman and rabbit eyelids were fixed in paraformaldehyde, serial sectioned (50 μm) using a cryotome and imaged by brightfield and reflectance microscopy. Eyelid regions (MG, muscle, tarsus and dermis) were then illuminated by a 100 μm spot using a infrared enhanced white light source. Transmission spectra over a 550-950 nm range were then measured using a spectrometer and differences compared using two-way analysis of variance.ResultsBrightfield microscopy of both human and rabbit eyelid tissue showed a marked decrease in light transmission for MG acini compared to other eyelid tissues. In rabbit, the dermis showed 5× and the muscle showed 2× more light transmission compared to MG (P

People can quickly and accurately compute not only the mean size of a set of items but also the size variability of the items. However, it remains unknown how these statistics are estimated. Here we show that neither parallel access to all items nor random subsampling of just a few items is sufficient to explain participants' estimations of size variability. In three experiments, we had participants compare two arrays of circles with different variability in their sizes. In the first two experiments, we manipulated the congruency of the range and variance of the arrays. The arrays with congruent range and variability information were judged more accurately, indicating the use of range as a proxy for variability. Experiments 2B and 3 showed that people also are not invariant to low- or mid-level visual information in the arrays, as comparing arrays with different low-level characteristics (filled vs. outlined circles) led to systematic biases. Together, these experiments indicate that range and low- or mid-level properties are both utilized as proxies for variability discrimination, and people are flexible in adopting these strategies. These strategies are at odds with the claim of parallel extraction of ensemble statistics per se and random subsampling strategies previously proposed in the literature.

The current study examines the association between parental support and adolescent sleep under varying levels of family stress. Participants included 316 adolescents (Mage  = 16.40 years, 43% male) and their parents (Mage  = 45.67 years, 91% mothers) from diverse ethnic backgrounds. Both adolescents and parents completed questionnaires and adolescents wore wrist actigraphs and completed self-reports on their sleep for 7 consecutive days. Results indicated that under contexts of family stress, more parental support was linked to longer sleep duration, less sleep variability, and less time spent awake during the night. Findings suggest that under contexts of family stress, cohesive family relationships may provide a sense of stability and security that is necessary for healthful sleep.

BACKGROUND:Both external levator resection (ELR) and Müller's muscle-conjunctival resection (MMCR) are procedures well known to improve marginal reflex distance (MRD1) in patients with ptosis. This study aims to understand differential post-operative changes in eyelid contour for MMCR and ELR surgery. METHODS:In this cross-sectional cohort study, patients affected by involutional ptosis were randomized into two groups: those who underwent ELR or MMCR surgery. Pre-operative and late post-operative photographs were obtained. Digital analysis of the lid contour was performed by measuring the vertical distance from a line intersecting the center of the pupil to the eyelid margin at 10 positions at 2 mm intervals. Mean distance at each position was compared pre- and post-operatively between the groups. RESULTS:The final sample included 60 eyes from 39 patients, 30 eyes per group. At each time point there was significant variation in height across the eyelid (p

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.