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We aimed to assess the associations of peripheral neuropathy (PN) with vision and hearing impairment among adults aged ≥40 years who attended the lower-extremity disease exam for the National Health and Nutrition Examination Survey (United States, 1999–2004). Overall, 11.8% (standard error (SE), 0.5) of adults had diabetes, 13.2% (SE, 0.5) had PN (26.6% (SE, 1.4) with diabetes, 11.4% (SE, 0.5) without diabetes), 1.6% (SE, 0.1) had vision impairment, and 15.4% (SE, 1.1) had hearing impairment. The prevalence of vision impairment was 3.89% (95% CI: 2.99, 5.05) among adults with PN and 1.29% (95% CI: 1.04, 1.60) among adults without PN (P < 0.001). After adjustment, PN was associated with vision impairment overall (odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.03, 2.13) and among adults without diabetes (OR = 1.80, 95% CI: 1.17, 2.77) but not among adults with diabetes (P for interaction = 0.018). The prevalence of hearing impairment was 26.5% (95% CI: 20.4, 33.7) among adults with PN and 14.2% (95% CI: 12.4, 16.3) among adults without PN (P < 0.001). The association of PN with moderate/severe hearing impairment was significant overall (OR = 2.55, 95% CI: 1.40, 4.64) and among adults without diabetes (OR = 3.26, 95% CI: 1.80, 5.91). Overall, these findings suggest an association between peripheral and audiovisual sensory impairment that is unrelated to diabetes.

Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 years or older while increasing in adults under age 50 years. Understanding these trends is challenging because of the multiple related time scales of age, diagnosis period, and birth cohort. We analyzed incidence rates of rectal, distal colon, and proximal colon cancer for individuals aged 20 years or more from the Surveillance, Epidemiology, and End Results Program for diagnosis years 1978–2017. We used a 2-stage generalized linear model to determine age, period, and cohort effects for CRC incidence. We first estimated birth cohort effects among people under age 45 years. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people aged 45 years or more. There was no evidence of period effects for people under age 45 years. Risks of rectal and distal colon cancer increased for later birth cohorts. Compared with the 1943–1952 birth cohort, the 1983–1992 birth cohort had 2.2 times the risk of rectal cancer, 1.9 times the risk of distal colon cancer, and 1.3 times the risk of proximal colon cancer. For people aged ≥45 years, period effects showed declines in CRC risk that were attributable to screening.

Racial/ethnic and sex/gender disparities in sleep duration have been documented in adolescence and adulthood. Identifying racial/ethnic and sex/gender differences in sleep duration trajectories from adolescence to adulthood can inform interventions on the developmental periods individuals are most at risk for short sleep duration. We examined racial/ethnic and sex/gender differences in self-reported sleep duration trajectories from adolescence to adulthood using data from waves I, III, IV, and V of the National Longitudinal Study of Adolescent to Adult Health (1994–2018; n = 12,593). Multigroup growth mixture modeling was used to enumerate sleep duration trajectories from adolescence to adulthood. There were 3 common trajectory types across race/ethnicity and sex/gender groups: 1) consistent increasing short sleepers (i.e., increasing probability of short sleep into adulthood) (67.3%); 2) late-onset short sleepers (i.e., no probability of short sleep duration in adolescence until adulthood) (20.2%); and 3) early-onset short sleepers (i.e., declining probability of short sleep duration from adolescence into adulthood) (12.5%). The prevalence of the consistent-increasing trajectory was highest among Black male respondents, while late onset was highest among White female respondents and early onset greatest among Latinx male respondents. Findings underscore the need to intervene in early adolescence to prevent short sleep duration in adulthood.

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.

Multimorbidity (≥2 chronic conditions) is a common and important marker of aging. To better understand racial differences in multimorbidity burden and associations with important health-related outcomes, we assessed differences in the contribution of chronic conditions to hospitalization, skilled nursing facility admission, and mortality among non-Hispanic Black and non-Hispanic White older adults in the United States. We used data from a nationally representative study, the National Health and Aging Trends Study, linked to Medicare claims from 2011–2015 (n = 4,871 respondents). This analysis improved upon prior research by identifying the absolute contributions of chronic conditions using a longitudinal extension of the average attributable fraction for Black and White Medicare beneficiaries. We found that cardiovascular conditions were the greatest contributors to outcomes among White respondents, while the greatest contributor to outcomes for Black respondents was renal morbidity. This study provides important insights into racial differences in the contributions of chronic conditions to costly health-care utilization and mortality, and it prompts policy-makers to champion delivery reforms that will expand access to preventive and ongoing care for diverse Medicare beneficiaries.

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (−0.56 points (95% confidence interval: −1.63, 0.52) and −0.89 points (95% confidence interval: −2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Smoke-free housing policies are intended to reduce the deleterious health effects of secondhand smoke exposure, but there is limited evidence regarding their health impacts. We examined associations between implementation of a federal smoke-free housing rule by the New York City Housing Authority (NYCHA) and pediatric Medicaid claims for asthma, lower respiratory tract infections, and upper respiratory tract infections in the early post–policy intervention period. We used geocoded address data to match children living in tax lots with NYCHA buildings (exposed to the policy) to children living in lots with other subsidized housing (unexposed to the policy). We constructed longitudinal difference-in-differences models to assess relative changes in monthly rates of claims between November 1, 2015, and December 31, 2019 (the policy was introduced on July 30, 2018). We also examined effect modification by baseline age group (≤2, 3–6, or 7–15 years). In New York City, introduction of a smoke-free policy was not associated with lower rates of Medicaid claims for any outcomes in the early postpolicy period. Exposure to the smoke-free policy was associated with slightly higher than expected rates of outpatient upper respiratory tract infection claims (incidence rate ratio = 1.05, 95% confidence interval: 1.01, 1.08), a result most pronounced among children aged 3–6 years. Ongoing monitoring is essential to understanding long-term health impacts of smoke-free housing policies.

Few prospective studies have examined associations between diet quality and pancreatic ductal adenocarcinoma (PDAC), or comprehensively compared diet quality indices. We conducted a prospective analysis of adherence to the Healthy Eating Index (HEI)-2015, alternative HEI-2010, alternate Mediterranean diet (aMed), and 2 versions of Dietary Approaches to Stop Hypertension (DASH; Fung and Mellen) and PDAC within the National Institutes of Health (NIH)-AARP Diet and Health Study (United States, 1995–2011). The dietary quality indices were calculated using responses from a 124-item food frequency questionnaire completed by 535,824 participants (315,780 men and 220,044 women). We used Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each diet quality index and PDAC. During follow-up through 2011 (15.5-year median), 3,137 incident PDAC cases were identified. Compared with those with the lowest adherence quintile, participants with the highest adherence to the HEI-2015 (HR = 0.84, 95% CI: 0.75, 0.94), aMed (HR = 0.82, 95% CI: 0.73, 0.93), DASH-Fung (HR = 0.85, 95% CI: 0.77, 0.95), and DASH-Mellen (HR = 0.86, 95% CI: 0.77, 0.96) had a statistically significant, lower PDAC risk; this was not found for the alternative HEI-2010 (HR = 0.93, 95% CI: 0.83, 1.04). This prospective observational study supports the hypothesis that greater adherence to the HEI-2015, aMed, and DASH dietary recommendations may reduce PDAC.

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991–1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs–Boston University–Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school–level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players’ lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE.

Internet usage among adolescents has increased substantially over the last years, concurrently with emerging concerns that an abusive use is associated with detrimental health outcomes. Our objective was to examine the association between age of first exposure and heavy Internet usage in different domains. Data from the 2018 wave of the Programme for International Student Assessment (PISA) were retrieved. This included a total of 317,443 participants (49.2% boys) aged 15 and 16 years from 52 countries. Data from both Internet use and age of first exposure were retrieved and used to conduct metanalyses with random effects. Adolescents reporting an age of first exposure of Internet usage at ≥ 13 years old had the lowest odds for heavy Internet use (> 2 h/day) (reference group: ≤ 9 years) during weekends (odds ratio, 0.41 [95% CI, 0.35–0.48]), weekdays (odds ratio, 0.45 [95% CI, 0.37–0.56]), and during school time (odds ratio (odds ratio, 0.86 [95% CI, 0.77–0.96]) even when adjusted for sex, socioeconomic status, and country. A stronger association was observed in adolescents from South and Central America and Eastern Mediterranean regions in the domain of weekends and weekdays. The results indicate that early internet exposure is associated with heavy Internet use, particularly during weekends and weekdays, regardless the geographical region, in a linear fashion. Further research should aim to examine if better education and parental control in specific areas may avoid excessive Internet use that possibly have a negative influence on both mental and physical health. Supplementary Information The online version contains supplementary material available at 10.1007/s00787-021-01869-5.

The impact of school-closings on adolescents’ mental health and well-being in the management of the ongoing COVID-19 pandemic is subject to ongoing public debate. Reliable data to inform a balanced discussion are limited. Drawing on a large ongoing multi-site project in Germany, we assessed differences in self-reported psychopathology in a matched convenience-sample of adolescents assessed pre- (November 26, 2018 to March 13, 2020; n = 324) and post the first lockdown (March 18, 2020 to August 29, 2020; n = 324) early 2020 in Germany. We found no evidence for an increase in emotional and behavioral problems, depression, thoughts of suicide or suicide attempts, eating disorder symptoms, or a decrease in general health-related quality of life. Reported suicide plans significantly decreased from 6.14 to 2.16%. Similarly, conduct problems decreased in the post-lockdown period. Family risk-factors did not moderate these findings. The influence of socioeconomic status on emotional and behavioral problems as well as depression decreased during the lockdown. Based on the present findings, the first school-closing in Germany had no immediate and severe impact on adolescents’ well-being. However, caution is warranted as our data covers a fairly small, affluent sample over a limited time-span and long-term consequences cannot be ruled out.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998–2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

It has been reported that residents of low–socioeconomic-status (SES) neighborhoods have a higher risk of developing cardiovascular disease (CVD). However, most of the previous studies focused on 1-time measurement of neighborhood SES in middle-to-older adulthood and lacked demographic diversity to allow for comparisons across different race/ethnicity and sex groups. We examined neighborhood SES in childhood and young, middle, and older adulthood in association with CVD risk among Black and White men and women in the Atherosclerosis Risk in Communities Study (1996–2019). We found that lower neighborhood SES in young, middle, and older adulthood, but not in childhood, was associated with a higher risk of CVD later in life. When compared with the highest quartile, the lowest quartile of neighborhood SES in young, middle, and older adulthood was associated with 18% (hazard ratio (HR) = 1.18, 95% confidence interval (CI): 1.02, 1.36), 21% (HR = 1.21, 95% CI: 1.04, 1.39), and 12% (HR = 1.12, 95% CI: 0.99, 1.26) increases in the hazard of total CVD, respectively. The association between lower neighborhood SES in older adulthood and higher CVD hazard was particularly strong among Black women. Our study findings support the role of neighborhood SES in cardiovascular health in both Black and White adults.

Studies of statins and amyotrophic lateral sclerosis (ALS) incidence and survival have had conflicting findings possibly related to difficulties with confounding by indication. We considered potency of statins used and duration of use to explore confounding by indication. Within the Clalit Health Services in Israel, we identified 948 ALS case patients from 2004 through 2017 and matched them with 1,000 control subjects each. Any statin use up to 3 years before ALS onset was not associated with ALS incidence but was associated with a reduced hazard ratio (HR) for death. Odds of ALS did not vary by statin potency, but use of only lower-potency statins was associated with longer survival (HR = 0.82, 95% CI: 0.68, 0.98), whereas the association with higher-potency statins was null compared with those case patients who did not use statins. However, duration of statin use appeared to account for these findings. Those who used statins only up to 3 years had longer survival (HR = 0.77, 95% CI: 0.61, 0.96) than did case patients who did not use statins, but those who used statins for >3 years did not. Although other explanations are possible, these findings could suggest a protective effect of statins on ALS survival that is partially masked by a worse prognosis from underlying reasons for taking statins that deserves further exploration.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women’s Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations.

To evaluate the association of nonesterified fatty acids (NEFA) with dysglycemia in older adults, NEFA levels were measured among participants in the Cardiovascular Health Study (United States; enrolled 1989–1993). Associations with insulin sensitivity and pancreatic β-cell function, and with incident type 2 diabetes mellitus (DM), were examined. The sample comprised 2,144 participants (aged 77.9 (standard deviation, 4.5) years). Participant data from the Cardiovascular Health Study visit in 1996–1997 was used with prospective follow-up through 2010. Fasting and postload NEFA showed significant associations with lower insulin sensitivity and pancreatic β-cell function, individually and on concurrent adjustment. Over median follow-up of 9.7 years, 236 cases of DM occurred. Postload NEFA were associated with risk of DM (per standard deviation, hazard ratio = 1.18, 95% confidence interval: 1.08, 1.29), but fasting NEFA were not (hazard ratio = 1.12, 95% confidence interval: 0.97, 1.29). The association for postload NEFA persisted after adjustment for putative intermediates, and after adjustment for fasting NEFA. Sex and body mass index modified these associations, which were stronger for fasting NEFA with DM in men but were accentuated for postload NEFA in women and among leaner individuals. Fasting and postload NEFA were related to lower insulin sensitivity and pancreatic β-cell function, but only postload NEFA were associated with increased DM. Additional study into NEFA metabolism could uncover novel potential targets for diabetes prevention in elders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause severe placental lesions leading rapidly to intrauterine fetal death (IUFD). From August 2020 to September 2021, in the pathology department of Toulouse Oncopole, we analyzed 50 placentas from COVID-19-positive unvaccinated mothers. The purpose of our study is to describe the clinicopathological characteristics of these placental damages and to understand the pathophysiology. Ten of them (20%) showed placental lesions with positive immunohistochemistry for SARS-CoV-2 in villous trophoblasts. In five cases (10%), we observed massive placental damage associating trophoblastic necrosis, fibrinous deposits, intervillositis, as well as extensive hemorrhagic changes due to SARS-CoV-2 infection probably responsible of IUFD by functional placental insufficiency. In five other cases, we found similar placental lesions but with a focal distribution that did not lead to IUFD but live birth. These lesions are independent of maternal clinical severity of COVID-19 infection because they occur despite mild maternal symptoms and are therefore difficult to predict. In our cases, they occurred 1-3 weeks after positive SARS-CoV-2 maternal real-time polymerase chain reaction testing and were observed in the 2nd and 3rd trimesters of pregnancies. When these lesions are focal, they do not lead to IUFD and can be involved in intrauterine growth restriction. Our findings, together with recent observations, suggest that future pregnancy guidance should include stricter pandemic precautions such as screening for a wider array of COVID-19 symptoms, enhanced ultrasound monitoring, as well as newborn medical surveillance.

Case reports and a pharmacovigilance analysis have linked glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with anaphylactic reactions, but real-world evidence for this possible association is lacking. Using databases from the United Kingdom (Clinical Practice Research Datalink) and the United States (Medicare, Optum (Optum, Inc., Eden Prairie, Minnesota), and IBM MarketScan (IBM, Armonk, New York)), we employed a new-user, active comparator study design wherein initiators of GLP-1 RAs were compared with 2 different active comparator groups (initiators of dipeptidyl peptidase 4 (DPP-4) inhibitors and initiators of sodium-glucose cotransporter 2 (SGLT-2) inhibitors) between 2007 and 2019. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for an anaphylactic reaction. Database-specific HRs were pooled using random-effects models. Compared with the use of DPP-4 inhibitors (n = 1,641,520), use of GLP-1 RAs (n = 324,098) generated a modest increase in the HR for anaphylactic reaction, with a wide 95% CI (36.9 per 100,000 person-years vs. 32.1 per 100,000 person-years, respectively; HR = 1.15, 95% CI: 0.94, 1.42). Compared with SGLT-2 inhibitors (n = 366,067), GLP-1 RAs (n = 259,929) were associated with a 38% increased risk of anaphylactic reaction (40.7 per 100,000 person-years vs. 29.4 per 100,000 person-years, respectively; HR = 1.38, 95% CI: 1.02, 1.87). In this large, multisite population-based cohort study, GLP-1 RAs were associated with a modestly increased risk of anaphylactic reaction when compared with DPP-4 inhibitors and SGLT-2 inhibitors.

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women’s Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women.

The volume of E-commerce transactions had accelerated on huge scale due to COVID-19. Telemedicine comes under the segment of E-commerce, where the patients can get their treatments from isolates. Patients’ information security is a basic challenge in this COVID-19 telemedicine segment. The majority of the non-obtrusive and non-emergency patients are encouraged and treated distantly from their secludes without the inclusion of COVID-19 transmission. Anxiety, depressive disorders, stress, dementia, mood disorder, OCD, aggression, etc. are the critical mental challenges that have abruptly occurred during this COVID period. The present work focused on “New Normal Mode” of COVID-19 telepsychiatry so that the patients’ mental illness can be treated remotely in a secure way. An episode of dual neural-genetic firefly (DNGF) has been proposed on COVID-19 "New Normal Mode" 2nd wave telepsychiatry. The pool of transmission keys was generated with the help of firefly algorithm, neural perceptron, and genetic operations. Besides these, the proposed DNGF keys are effective to be used for different online psychiatric transactions. The objectivity of this paper is to generate a robust pool of transmission keys in order to nullify different types of intruding. It has effectively cleared Avalanche test and Strict Avalanche test. The outcome of parameterized functional security test has been recorded with adequacy. These were: 0.327933, 0.350467, 0.332533, 0.317867, and 0.350267 on the generated pool of DNGF. The correlation coefficient between the key generation time and parameterized functional security has been found to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r_{GT,FS} = - 0.53404.$$\end{document}rGT,FS=-0.53404. Distinctive mathematical arranged examinations were directed on the proposed key pool. It has shown better reasonability on the part of the COVID-19 2nd wave telepsychiatry, which is a component of E-commerce.

We recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women’s Health Initiative (1993–present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables.

Simplified drug regimens may improve retention in care for persons with chronic diseases. In April 2013, South Africa adopted a once-daily single-pill human immunodeficiency virus (HIV) treatment regimen as the standard of care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offered a real-world test of the impact of simplified drug-delivery mechanisms on patient behavior. Using a quasi-experimental regression discontinuity design, we assessed retention in care among patients starting HIV treatment just before and just after the guideline change. The study included 4,484 patients starting treatment at a large public sector clinic in Johannesburg, South Africa. The share of patients prescribed a single-pill regimen increased by over 40 percentage points between March and April 2013. Initiating treatment after the policy change was associated with 11.7–percentage-points’ higher retention at 12 months (95% confidence interval: −2.2, 29.4). Findings were robust to different measures of retention, different bandwidths, and different statistical models. Patients starting treatment early in HIV infection—a key population in the test-and-treat era—experienced the greatest improvements in retention from single-pill regimens.

Recent studies have provided key information about SARS-CoV-2 vaccines’ efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptible individuals between vaccinated and unvaccinated groups. We examined the extent to which biases occur under different scenarios and assessed whether serological testing has the potential to correct this bias. By identifying nonvaccine antibodies, these tests could identify individuals with prior infection. We found that in scenarios with high baseline VE, differential depletion of susceptible individuals created minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE was lower, the bias for leaky vaccines (which reduce individual probability of infection given contact) was larger and should be corrected for by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serological testing, on this critical variable.

Background Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a simplification of the duodenal switch (DS) in which the alimentary limb is eliminated, and the common channel is lengthened from 200 to 300 cm. Short-term results have demonstrated that SADI-S is safe and reproducible and that weight loss and comorbidities resolution are comparable to biliopancreatic diversion or DS. Objective To analyze the long-term outcomes of SADI-S. Methods From May 2007 to December 2015, 164 patients were consecutively submitted to a one-step SADI-S. The mean age was 47 years, and the mean body mass index (BMI) was 45.8 kg/m2. A total of 101 patients had type 2 diabetes, 91 arterial hypertension, 81 obstructive apnea, and 118 dyslipidemia. Limb length was 200 cm in 50 cases, 250 cm in 99, and 300 cm in 15. Results There was no mortality. One patient had a gastric leak, and 2 patients had an anastomotic leak. A total of 25% of the patients were lost to follow-up at 10 years. Excess weight loss and total weight loss were 87% and 38% at 5 years and 80% and 34% at 10 years. A total of 12 patients were submitted to revisional surgery for hypoproteinemia. Preoperatively 41 diabetics were under insulin treatment; at 5 years, 7 remained with insulin and 12 at 10 years. Mean glycemia was 104 mg/dL at 5 years and 118 mg/dL at 10 years. Mean HbA1c was 5.51% at 5 years and 5.86 at 10 years. Conclusion In the long term, SADI-S offers satisfactory weight loss and comorbidities resolution. Graphical Abstract

Endometriosis, psoriasis, and psoriatic arthritis (PsA) are chronic inflammatory disorders whose etiologies remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bidirectional associations between laparoscopically confirmed endometriosis and physician-diagnosed psoriasis and PsA in the Nurses’ Health Study II cohort (n = 116,429, United States, 1991–2013). We confirmed 4,112 incident cases of laparoscopically confirmed endometriosis (mean age at diagnosis = 40.3 years) and 697 validated physician-diagnosed cases of psoriasis (mean age at diagnosis = 43.6 years), 110 of which presented with concomitant PsA. A history of psoriasis with concomitant PsA was associated with a 2-fold higher risk of endometriosis (hazard ratio (HR) = 2.01, 95% CI: 1.23, 3.30); however, no association was observed between psoriasis without PsA and endometriosis risk (HR = 0.93, 95% CI: 0.68, 1.26). When endometriosis was the exposure, it was not associated with a risk of subsequent psoriasis (HR = 1.28, 95% CI: 0.95, 1.72). The risk of psoriasis with PsA was notably higher; however, the sample size was small and the confidence intervals wide (HR = 1.77, 95% CI: 0.89, 3.52). Our findings suggest that psoriasis with concomitant PsA is associated with greater risk of laparoscopically confirmed endometriosis. In addition, there was a suggestive association between endometriosis diagnosis and subsequent risk of psoriasis with PsA.

We aimed to determine whether intake of pesticide residues from fruits and vegetables was associated with glioma. Within 3 prospective cohorts from 1998–2016—the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow-up Study—we computed multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CI) for glioma by quintiles of intake of low- and high-pesticide-residue fruits and vegetables using Cox proportional hazards regression. Fruits and vegetables were categorized as high or low residue using a validated method based on pesticide surveillance data. We confirmed 275 glioma cases across 2,745,862 person-years. A significant association was observed between intake of high-residue fruits and vegetables and glioma in NHS (MVHR = 2.99, 95% CI: 1.38, 6.44 comparing highest with lowest quintile, P for trend = 0.02). This was not identified in NHSII (MVHR = 0.52, 95% CI: 0.19, 1.45, P for trend = 0.20) or Health Professionals Follow-up Study (MVHR = 1.01, 95% CI: 0.42, 2.45, P for trend = 0.39). No significant associations were observed by intake of low-residue fruits and vegetables; overall intake was not significantly associated with glioma in any cohort. We found no evidence for an inverse relationship of fruit and vegetable intake with glioma. Although limited in power, this study suggests a possible association between fruit-and-vegetable pesticide residue intake and risk of glioma that merits further study.

We estimated the trends and correlates of vaccine hesitancy and its association with subsequent vaccine uptake among 5,458 adults in the United States. Participants belonged to the Communities, Households, and SARS-CoV-2 Epidemiology COVID (CHASING COVID) Cohort, a national longitudinal study. Trends and correlates of vaccine hesitancy were examined longitudinally in 8 interview rounds from October 2020 to July 2021. We also estimated the association between willingness to vaccinate and subsequent vaccine uptake through July 2021. Vaccine delay and refusal decreased from 51% and 8% in October 2020 to 8% and 6% in July 2021, respectively. Compared with non-Hispanic (NH) White participants, NH Black and Hispanic participants had higher adjusted odds ratios (aOR) for both vaccine delay (for NH Black, aOR = 2.0 (95% confidence interval (CI): 1.5, 2.7), and for Hispanic, 1.3 (95% CI: 1.0, 1.7)) and vaccine refusal (for NH Black, aOR = 2.5 (95% CI: 1.8, 3.6), and for Hispanic, 1.4 (95% CI: 1.0, 2.0)) in June 2021. COVID-19 vaccine hesitancy, compared with vaccine-willingness, was associated with lower odds of subsequent vaccine uptake (for vaccine delayers, aOR = 0.15, 95% CI: 0.13, 0.18; for vaccine refusers, aOR = 0.02; 95% CI: 0.01, 0.03 ), adjusted for sociodemographic factors and COVID-19 history. Vaccination awareness and distribution efforts should focus on vaccine delayers.

In today’s world, life-threatening diseases have become a pre-eminent issue in healthcare due to the higher mortality rate. It is possible to lower this mortality rate by utilizing healthcare intelligence to detect diseases early. Patient’s medical data is stored in the EHR system, which is kept up to date by the healthcare provider. Data mining techniques like Association Rule Mining can detect a patient’s disease from their symptoms using digital healthcare data stored in the EHR system. Association rule mining’s efficacy can be improved by using global data from various EHR systems. It mandates that all EHR systems exchange healthcare records to a central server. When personal health information is made available on an untrusted server, several privacy laws may be violated. As a result, the challenge of privacy preserving distributed healthcare data mining has become a well-known study field in the healthcare industry. This research uses an efficient ElGamal homomorphic encryption technique to protect privacy in a distributed association rule mining. The proposed approach to discover the risk factor of most life-threatening diseases like breast cancer and heart disease with its symptoms and discuss the scope for combating COVID-19. Theoretical analysis of the proposed approach shows that it is efficient and maintains privacy in an insecure communication environment. An experimental study with a real dataset shows the proposed approach’s benefit compared to the local single EHR system results.

Background Little is known about voluntary divestment of firearms among US firearm owners. Here, we aim to estimate the proportion of handgun owners who divest their handguns in the years following their initial acquisition; examine the timing, duration, and dynamics of those divestments; and describe characteristics of those who divest. Methods We use data from the Longitudinal Study of Handgun Ownership and Transfer, a cohort of registered voters in California with detailed information on 626,756 adults who became handgun owners during the 12-year study period, 2004–2016. For the current study, persons were followed from the time of their initial handgun acquisition until divestment, loss to follow-up, death, or the end of the study period. We describe the cumulative proportion who divest overall and by personal and area-level characteristics. We also estimate the proportion who reacquired handguns among persons who divested. Results Overall, 4.5% (95% CI 4.5–4.6) of handgun owners divested within 5 years of their first acquisition, with divestment relatively more common among women and among younger adults. Among those who divested, 36.6% (95% CI 35.8–37.5) reacquired a handgun within 5 years. Conclusions Handgun divestment is rare, with the vast majority of new handgun owners retaining them for years.

Sugar chain immobilized polymer particles having both magnetic and fluorescent properties can be expected to be useful in a wide variety of biomedical applications such as the detection, separation, and purification of proteins, viruses, or bacteria, because sugar chains specifically adsorb them. Since high magnetic responsiveness is required for such applications, we attempted to fabricate core-shell particles consisting of a submicron-sized magnetic core and a thin polymer shell (nano- to dozens of nanometers thick) that incorporates a fluorescent dye, with sugar molecules immobilized on the surface. Soap-free emulsion polymerization using methyl methacrylate (MMA) monomer and potassium persulfate (KPS) initiator in the presence of aminopropyltrimethoxysilane-treated Ni particles, octyl-β-D-glucopyranoside (octyl-glc), and rhodamine B (RhB) produced a glucose-immobilized fluorescent PMMA thin shell on a Ni particle (Ni/PMMA/RhB/octyl-glc). Electrostatic interaction was used both to incorporate RhB into the PMMA shell and to coat the Ni core with the PMMA-RhB shell. Glucose was immobilized on the PMMA shell by embedding a hydrophobic octyl group derived from octyl-glc in the PMMA matrix, and the resulting sugar-immobilized PMMA shell was able to adsorb protein (concanavalin A; a protein that specifically adsorbs glucose). The resulting Ni/PMMA/RhB/octyl-glc particles were well-dispersed in water, detected by highly sensitive fluorescence techniques, and could be collected by a magnet within 10 sec. They are expected to be applied to detect biological substances such as various proteins and viruses by changing the glucose moiety of the particle surface to other functional glycans. Supplementary information The online version contains supplementary material available at 10.1007/s00396-022-04945-7.

Background Traditionally, the herb Byttneria pilosa Roxb. is used for bone fractures, boils, scabies, rheumatalgia, snake bites, syphilis, elephantiasis, poisoning, and eye infection. Scientific reports suggest that it has significant anti-inflammatory, analgesic, anti-diarrheal, anxiolytic, locomotion, sedative and anti-obesity effects. This study aims at the investigation of the phytochemical and pharmacological properties of the ethanol extract of this herb. Methods Fresh whole plant was extracted with absolute ethanol. A preliminary phytochemical investigation was followed by the evaluation of thrombolytic, anti-inflammatory, and anti-nociceptive activities by applying human clotted blood lysis, egg albumin, and acetic acid-induced writhing models, respectively. Results Phytochemical investigation suggests that B. pilosa possesses alkaloids, flavonoids, glycosides, terpenoids, tannins, saponins, and reducing sugars. The extract exhibited clot lysis and anti-inflammatory effects in a concentration-dependent manner. B. pilosa extract at 250 and 500 mg/kg also showed significant (p Swiss albino mice. Conclusion The B. pilosa ethanol extract contains many important secondary metabolites and has thrombolytic, anti-inflammatory, and anti-nociceptive activities. More research is necessary on this hopeful medicinal herb.

This work was supported by grants from Ministerio de Ciencia e Innovacion (DI-16-08943), Junta de Andalucia, Consejeria de Economia, Conocimiento, Empresas y Universidad and FEDER funds (AT17_5489_USE), Centro para el Desarrollo Tecnologico Industrial (IDI-20180051) and Corporacion Tecnologica de Andalucia (17/957)., Purpose Determination of Gluten Immunogenic Peptides (GIP) in feces is a direct tool for gluten exposure detection. The sensitivity of GIP detection methods for cases of unintentional low gluten intakes is unknown. We studied the interindividual variability in the kinetic of excretion under homogeneously controlled dietary conditions, and the sensitivity of fecal GIP tests after low amounts of punctual gluten ingestions. Methods Participants (n = 20) followed the same gluten-free menu for 12 days in which two separated doses of gluten (50 mg and 2 g) were ingested and all the depositions were collected. GIP from stool samples were analyzed by ELISA and lateral flow immunoassay (LFIA) tests. Results Most participants had detectable GIP after 50 mg and 2 g gluten ingestions using ELISA test (72.2% and 95%, respectively), whereas the LFIA test showed less sensitivity (22.2% and 80%, respectively). GIP were detected at higher either frequency or concentration in the range of 12–36 h after 50 mg intake, and 12–84 h after 2 g consumption. Considering this period, diagnostic sensitivity of GIP detection after a single 50 mg ingestion may be significatively increased analyzing three stool samples per individual. High variability among participants was found in the time and amount of GIP excretion; however, some individuals showed common patterns for both gluten intakes. Conclusion Sporadic gluten exposure detection may require several fecal samples to achieve level of sensitivity above 90%. Interindividual variability in the dynamic of GIP excretion may suggest patterns of gluten metabolism., Instituto de Salud Carlos III Spanish Government European Commission DI-16-08943, Junta de Andalucia Consejeria de Economia, Conocimiento, Empresas y Universidad European Commission AT17_5489_USE, Centro para el Desarrollo Tecnologico Industrial IDI-20180051, Corporacion Tecnologica de Andalucia 17/957

Background: Pregnancy-related risk factors for necrotizing fasciitis are poorly understood. We investigated pregnancy-related characteristics associated with the long-term risk of developing necrotizing fasciitis, a rare life-threatening infectious disease. Methods: We analyzed a longitudinal cohort of 1,344,996 parous women in Quebec, Canada between 1989 and 2020. The main exposure measures included complications of pregnancy such as gestational diabetes, preterm delivery, metabolic disorder, and other maternal characteristics. We followed the women over time to identify future hospitalizations for necrotizing fasciitis up to three decades after delivery. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association of pregnancy characteristics with risk of necrotizing fasciitis in time-varying Cox proportional hazards regression models. Results: A total of 420 women were hospitalized for necrotizing fasciitis during follow-up, including 83 (19.8%) with diabetes-related necrotizing fasciitis. The incidence of necrotizing fasciitis was elevated for women with gestational diabetes (2.9 per 100,000 person-years), preterm delivery (3.2 per 100,000 person-years), and metabolic disorders (5.4 per 100,000 person-years), compared with no pregnancy complication (1.1 per 100,000 person-years). Compared with no pregnancy complication, gestational diabetes was associated with 1.87 times the risk (95% CI 1.38-2.53), preterm delivery with 2.10 times the risk (95% CI 1.65-2.66), and metabolic disorder with 3.72 times the risk (95% CI 2.92-4.74) of developing necrotizing fasciitis over time. Pregnancy complications were more strongly associated with the risk of necrotizing fasciitis 5 years or more after delivery. Conclusions: Complications of pregnancy may be associated with the long-term risk of necrotizing fasciitis in women.

Siblings of children with chronic disorders are at increased risk of psychosocial problems. The risk may be exacerbated when the chronic disorder is rare and limited medical knowledge is available, due to more uncertainty and feelings of isolation. We examined mental health, parent-child communication, child-parent relationship quality, and social support among 100 children aged 8 to 16 years (M age 11.5 years, SD = 2.2; 50.0% boys, 50.0% girls). Fifty-six were siblings of children with rare disorders, and 44 were controls. The siblings of children with rare disorders (herein, siblings) were recruited from a resource centre for rare disorders and comprised siblings of children with a range of rare disorders including neuromuscular disorders and rare chromosomal disorders with intellectual disability. Controls were recruited from schools. Self-reported child mental health was significantly poorer for siblings compared to controls (effect size difference d = 0.75). Parent-reported child mental health was not significantly different between the groups (d = -0.06 to 0.16). Most child-parent relationships (anxiety/avoidance; mothers/fathers) were significantly poorer for siblings compared to controls (d = 0.47 to 0.91). There was no difference between groups in anxious relation with mother. Parent-child communication was significantly poorer for siblings compared to controls (d = -0.87 to -0.75). Social support was significantly poorer for siblings compared to controls (d = 0.61). We conclude that siblings of children with rare disorders display more psychosocial problems than controls. Interventions are indicated to prevent further maladjustment for siblings.

Purpose Cancer of unknown primary (CUP) is a metastasised cancer for which no primary lesion could be identified during life. Research into CUP aetiology with respect to dietary factors is particularly scarce. This study investigates whether meat consumption is associated with CUP risk. Methods Data was utilised from the prospective Netherlands cohort study that includes 1,20,852 participants aged 55–69 years. All participants completed a self-administered questionnaire on diet and other cancer risk factors at baseline. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and the Dutch Pathology Registry. A total of 899 CUP cases and 4111 subcohort members with complete and consistent dietary data were available for case–cohort analyses after 20.3 years of follow-up. Multivariable adjusted hazard ratios (HRs) were calculated using proportional hazards models. Results We found a statistically significant positive association with beef and processed meat consumption and CUP risk in women (multivariable adjusted HR Q4 vs. Q1 1.47, 95% CI 1.04–2.07, Ptrend = 0.004 and Q4 vs. Q1 1.53, 95% CI 1.08–2.16, Ptrend = 0.001, respectively), and a non-significant positive association with processed meat consumption and CUP risk in men (multivariable adjusted HR Q4 vs. Q1 1.33, 95% CI 0.99–1.79, Ptrend = 0.15). No associations were observed between red meat (overall), poultry or fish consumption and CUP risk. Conclusion In this cohort, beef and processed meat consumption were positively associated with increased CUP risk in women, whereas a non-significant positive association was observed between processed meat consumption and CUP risk in men.

CPS1 deficiency is an inborn error of metabolism caused by loss-of-function mutations in the CPS1 gene, catalyzing the initial reaction of the urea cycle. Deficiency typically leads to toxic levels of plasma ammonia, cerebral edema, coma, and death, with the only curative treatment being liver transplantation; due to limited donor availability and the invasiveness and complications of the procedure, however, alternative therapies are needed. Induced pluripotent stem cells offer an alternative cell source to partial or whole liver grafts that theoretically would not require immune suppression regimens and additionally are amenable to genetic modifications. Here, we genetically modified CPS1 deficient patient-derived stem cells to constitutively express human codon optimized CPS1 from the AAVS1 safe harbor site. While edited stem cells efficiently differentiated to hepatocyte-like cells, they failed to metabolize ammonia more efficiently than their unedited counterparts. This unexpected result appears to have arisen in part due to transgene promoter methylation, and thus transcriptional silencing, in undifferentiated cells, impacting their capacity to restore the complete urea cycle function upon differentiation. As pluripotent stem cell strategies are being expanded widely for potential cell therapies, these results highlight the need for strict quality control and functional analysis to ensure the integrity of cell products.

Clostridium perfringens is an important food-borne zoonotic pathogen and a member of the commensal gut microbiome of many mammals. Predisposing factors such as coinfection with other pathogens or diet change can, however, cause overgrowth and subsequent disease development. Here we investigated the occurrence of C. perfringens in a free-ranging badger population with up to 100% prevalence of herpesvirus infection. Herpesvirus reactivation is known to be associated with increased susceptibility bacterial infections. PCR screening of rectal swabs from 69 free-ranging badgers revealed 15.9% (11/69, 95% CI = 9.1–26.3%) prevalence of detectable C. perfringens (Type A) DNA in the digestive tracts of assymptomatic animals. The results of Fisher’s exact test revealed C. perfringens detection was not biased by age, sex and seasons. However, badgers with genital tract gammaherpesvirus (MusGHV-1) reactivation (p = 0.007) and infection with a specific MusGHV-1 genotype (p = 0.019) were more prone to of C. perfringens proliferation, indicating coinfection biased dynamics of intestinal C. perfringens. An inclusion pattern analysis further indicated that, causally, MusGHV-1 reactivation potentiated C. perfringens detection. Whether or not specific MusGHV-1 genotype infection or reactivation plays a role in C. perfringens overgrowth or disease development in badgers will require further investigation. Nevertheless, a postmortem examination of a single badger that died of fatal disease, likely associated with C. perfringens, revealed MusGHV-1 detection in the small intestine.

Purpose The development of probiotics has seen tremendous growth over the years, with health benefits ranging from gut health to respiratory. We thus aimed to investigate the effects of probiotic Bifidobacterium lactis Probio-M8 (2 × 1010 log CFU/day) against acute respiratory tract infections (RTI), use of antibiotics, hospitalization period and elucidate the possible mechanisms of action in hospitalized young children. Method A prospective, randomized, double-blind and placebo-controlled study was performed in RTI-hospitalized children. Patients were randomized to either the probiotic (n = 60, mean age 13.81 ± 0.90 months) or placebo (n = 60, mean age 12.11 ± 0.73 months) which were administered upon admission, continued during hospitalization and 4-week post-discharged. RTI and gut health parameters were assessed at these time points using validated questionnaires while concentrations of inflammatory cytokines were assessed via oral swabs. Results Probio-M8 reduced the duration of nasal, pharyngeal and general flu-like symptoms compared to the placebo during the hospitalization period and 4-week post-discharged (P

Previous epidemiologic investigations suggested that maternal thyroid anomalies are a possible causal factor in attention-deficit hyperactivity disorder (ADHD) in progeny, yet clinical trials indicated that levothyroxine treatment was ineffective in preventing neurodevelopmental impairments. We used an Israeli cohort of 385,542 singleton births from 1999–2012 to explore the interrelated roles of maternal thyroid conditions, laboratory gestational thyroid hormone measurements, use of thyroid medications, and offspring ADHD. Analyses were performed using Cox proportional hazards models. Results indicated that maternal hypothyroidism diagnosis was associated with an elevated progeny ADHD hazard (adjusted hazard ratio = 1.14, 95% confidence interval = 1.10, 1.18). However, this association was unmitigated by gestational use of levothyroxine and was unexplained by maternal gestational thyroid hormone levels. Associations with gestational thyrotropin values and hypothyroxinemia were also observed but were robust only in mothers without other records indicative of a thyroid problem. Results indicated that maternal thyroid hypofunction was associated with progeny ADHD but possibly not due to a direct causal relationship. Instead, maternal thyroid hypofunction may serve as a proxy indicator for other factors that affect neurodevelopment through thyroid hormone independent pathways, which are thus unaffected by pharmaceutical treatments for thyroid hypofunction. Factors known to disrupt thyroid functioning should be examined for their independent ADHD-related effects.

The coronavirus pandemic and related restrictions impacted the daily lives of children and youth, partly due to the closure of schools and the absence of outdoor activities. The aim of this study was to investigate, quantify, and critically discuss the effect of the pandemic and related restrictions on consultations pertaining to depression and anxiety disorders in children and adolescents. This retrospective cross-sectional study was based on medical record data from the Disease Analyzer database (IQVIA) and included all children and adolescents aged 2–17 years with at least one visit to one of 168 German pediatric practices between April 2019 and December 2019 (n = 454,741) or between April 2020 and December 2020 (n = 417,979). The number of children and adolescents with depression and anxiety disorder diagnoses per practice and the prevalence of these diagnoses were compared for April 2020–December 2020 versus April 2019–December 2019. The number of children and adolescents with depression and anxiety diagnoses per practice increased in April 2020–December 2020 compared to the same period in 2019 (anxiety: + 9%, depression: + 12%). The increase was much greater in girls than in boys (anxiety: + 13% vs. + 5%; depression + 19% vs. + 1%). The prevalence of anxiety disorder increased from 0.31 to 0.59% (p

Anthropogenic land-use changes increase the frequency of interactions and habitat overlap between humans and macaques which play an important role in zoonotic disease transmission. This exploratory qualitative study aimed to examine connections between land-use change and macaque-human interactions and assess the chance of zoonotic disease transmission. We conducted ethnographic interviews and focus group discussions in Old Dhaka, Madaripur, and Chandpur, Bangladesh. Participants reported significant anthropogenic landscape transformations leading to increased human-macaque contact in the study areas. Participants also reported that all three sites underwent substantial landscape alteration from natural or agricultural land to a human-altered environment with roads, commercial, and residential buildings. Participants noted that the disappearance of forestland appeared to increase the macaque dependence on backyard fruit trees. Where rivers and ponds were filled to support local construction, macaques were also observed as becoming more dependent upon human water sources. These changed may help expanding the macaques' foraging areas, and they appear to be invading new areas where people are not culturally habituated to living with them. In response, many residents reported reacting aggressively toward the macaques, which they believed led to more bites and scratches. However, other respondents accepted the presence of macaques around their homes. Few participants considered macaques to be a source of disease transmission. This study revealed that local environmental changes, deforestation, urban expansion, construction, and water bodies' disappearance are linked to increasing human-macaque interactions. Understanding these interactions is critical to develop successful mitigation interventions at interfaces with a high risk for viral disease spillover.

Child and adolescent mental health systems are facing limited resources of available psychosocial interventions, often leading to long waiting lists for acceptance to treatment. We describe the feasibility of a short-term (8–10 sessions) psychological crisis intervention (CI) protocol for children and adolescents aged 8–17 years (n = 30, mean ± standard deviation 12.9 ± 2.4 years) who were referred to an outpatient mental health clinic due to suicidal ideation, aggression, severe anxiety, or extreme family conflict. The participants were assessed before and after the CI, and at a 3–6-months follow-up visit. The psychiatric assessments included clinical evaluation by a senior psychiatrist, and the completion of self-report questionnaires by both the participants and their parents. Following the establishment of the CI unit, the waiting lists for urgent cases were reduced from a median of 84 days in the two preceding years to 23 days in the following 3 years (H[2] = 18.5, p

Objectives of this study were to assess (1) prevalence of worries and symptoms of distress, and (2) perceived change in symptoms of distress by sociodemographic factors and preexisting vulnerabilities, among young Danes under the first COVID-19 related lockdown. Data were derived from online surveys, collected 7th–18th of May 2020. The study population included 11,245 young people (15–20 years of age), of which 1807 had participated in The Danish National Youth Study 2019 (DNYS19). Descriptive statistics and linear regressions analyses, including robust standard errors, were performed. All analyses were based on cross-sectional data, except analyses of preexisting vulnerabilities among responders from DNYS19. Few young people were very worried to get infected with coronavirus. Females reported a higher frequency of symptoms of distress than males. Perceived change in symptoms of distress, did not vary systematically based on age, cohabitation, nor physical health conditions. Individuals working, perceived a lower increase in symptoms of distress, than those studying etc. Females with symptoms of anxiety pre-pandemic, mental health disorders, and in families with economic hardship had a marginal higher perceived increase in symptoms of distress, than females without these difficulties. The tendencies were similar but nonsignificant among males, and for symptoms of depression pre-pandemic. In conclusion, during the lockdown, young females reported a higher frequency of symptoms of distress than males, and individuals with symptoms of anxiety pre-pandemic, mental health disorders, and in families with economic hardship were more likely to perceive the lockdown to be associated with an increase in symptoms of distress, than individuals without these difficulties.

Men who have sex with men (MSM) in the United States are stigmatized for their same-sex practices, which can lead to risky sexual behavior, potentiating risk for human immunodeficiency virus (HIV) infection. Improved measurement is necessary for accurately reporting and mitigating sexual behavior stigma. We added 13 sexual behavior stigma items to local surveys administered in 2017 at 9 sites in the Centers for Disease Control and Prevention’s National HIV Behavioral Surveillance system, which uses venue-based, time-sampling procedures to survey cisgender MSM in US Census Metropolitan Statistical Areas. We performed exploratory factor analytical procedures on site-specific (Baltimore, Maryland; Denver, Colorado; Detroit, Michigan; Houston, Texas; Nassau-Suffolk, New York; Portland, Oregon; Los Angeles, California; San Diego, California; and Virginia Beach-Norfolk, Virginia) and pooled responses to the survey items. A 3-factor solution—“stigma from family” (α = 0.70), “anticipated health-care stigma” (α = 0.75), and “general social stigma” (α = 0.66)—best fitted the pooled data and was the best-fitting solution across sites. Findings demonstrate that MSM across the United States experience sexual behavior stigma similarly. The results reflect the programmatic utility of enhanced stigma measurement, including tracking trends in stigma over time, making regional comparisons of stigma burden, and supporting evaluation of stigma-mitigation interventions among MSM across the United States.

BACKGROUND: Widespread vaccination is an essential component of the public health response to the COVID-19 pandemic, yet vaccine hesitancy remains pervasive. This prospective survey investigation aimed to measure the prevalence of vaccine hesitancy in a patient cohort at two urban emergency departments (EDs) and characterize underlying factors contributing to hesitancy. METHODS: Adult ED patients with stable clinical status (Emergency Severity Index 3-5) and without active COVID-19 disease or altered mental status were considered for participation. Demographic elements were collected as well as reported barriers/concerns related to vaccination and trusted sources of health information. Data were collected in person via a survey instrument proctored by trained research assistants. RESULTS: A total of 1,555 patients were approached, and 1,068 patients completed surveys (completion rate = 68.7%). Mean (±SD) age was 44.1 (±15.5) years (range = 18-93 years), 61% were female, and 70% were Black. A total of 31.6% of ED patients reported vaccine hesitancy. Of note, 19.7% of the hesitant cohort were health care workers. In multivariable regression analysis, Black race (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.62 to 6.85) and younger age (age 18-24 years-OR = 4.57, 95% CI = 2.66 to 7.86; age 25-35 years-OR = 5.71, 95% CI = 3.71 to 8.81) were independently associated with hesitancy, to a greater degree than level of education (high school education or less-OR = 2.27, 95% CI = 1.23 to 4.19). Hesitant patients were significantly less likely to trust governmental sources of vaccine information than nonhesitant patients (39.6% vs. 78.9%, p

Purpose Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. Methods In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. Results Postprandial concentrations of triacylglycerol (diet-effect: − 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: − 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC0–8 h) and first meal (iAUC0–4 h) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC4–8 h) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC0–8 h, dAUC0–4 h, and dAUC4–8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC4–8 h) tended to be lower after stearic-acid intake (p Conclusion Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.

Background Apprehensions of undocumented immigrants in the Rio Grande Valley sector of the U.S.-Mexico border have grown to account for nearly half of all apprehensions at the border. The purpose of this study is to report the prevalence, mechanism, and pattern of traumatic injuries sustained by undocumented immigrants who crossed the U.S.-Mexico border at the Rio Grande Valley sector over a span of 5 years and were treated at a local American College of Surgeons verified Level II trauma center. Methods A retrospective chart review was conducted from January 2014 to December 2019. Demographics, comorbidities, injury severity score (ISS), mechanism of injury, anatomical part of the body affected, hospital and ICU length of stay (LOS), and treatment costs were analyzed. Descriptive statistics for demographics, injury location and cause, and temporal trends are reported. The impact of ISS or surgical intervention on hospital LOS was analyzed using an analysis of covariance (ANCOVA). Results Of 178 patients, 65.2% were male with an average age of 31 (range 0–67) years old and few comorbidities (88.8%) or social risk factors (86%). Patients most commonly sustained injuries secondary to a border fence-related incident (33.7%), fleeing (22.5%), or motor vehicle accident (16.9%). There were no clear temporal trends in the total number of patients injured, or in causes of injury, between 2014 and 2019. The majority of patients (60.7%) sustained extremity injuries, followed by spine injuries (20.2%). Border fence-related incidents and fleeing increased risk of extremity injuries (Odds ratio (OR) > 3; p < 0.005), whereas motor vehicle accidents increased risk of head and chest injuries (OR > 4; p < 0.004). Extremity injuries increased the odds (OR: 9.4, p p Conclusion In addition to border fence related injuries, undocumented immigrants also sustained injuries while fleeing and in motor vehicle accidents, among others. Extremity injuries, which were more likely with border fence-related incidents, were the most common type. This type of injury often requires surgical intervention and, therefore, a longer hospital stay for severe injuries.

Background Intimate Partner Violence (IPV) is prevalent in women presenting to orthopaedic fracture clinics. Rates of IPV have increased during the COVID-19 global pandemic. Our aim was to determine the effect of educational experiences on IPV knowledge and IPV screening to inform best-practices in resident education. Methods Cross-sectional online survey of orthopaedic surgery residency programs in Canada. Demographics, IPV educational experiences, IPV knowledge, and frequency of IPV screening were collected via a modified version of the Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS). Descriptive statistics and regression modeling identified predictors of IPV knowledge and frequency of IPV screening. Results Responses were obtained from 105 orthopaedic residents; 84% participated in classroom training, 39% underwent mentorship training, 32% received both classroom training and mentorship, and 10% reported neither. Classroom training had no statistically significant association with IPV knowledge or frequency of IPV screening. Residents who received mentorship were 4.1 times more likely to screen for IPV (95% CI: 1.72–10.05), older residents were more likely to screen for IPV (OR: 8.3, 95% CI: 2.64–29.84), and senior residents were less likely to screen for IPV than junior residents (OR: 0.29, 95% CI: 0.09–0.82). Conclusions Classroom training was not associated with any effect on IPV knowledge nor the frequency of IPV screening. Educational efforts should be targeted at increasing mentorship opportunities in order to improve IPV screening practices in Canadian orthopaedic residents.