Search

Background&aimsSpecial Operations Forces Veterans (SOFV) have unique treatment needs stemming from multiple repeated forms of combat exposure resulting in a complex sequela of problems including alcohol misuse and post-traumatic stress symptoms. Current approved pharmacologic treatments for alcohol misuse and PTSD are lacking in adherence and efficacy, warranting novel treatment development. The current study examined the correlations between psychedelic treatment and changes in alcohol misuse among trauma exposed United States SOFV.MethodAn anonymous internet-based survey was conducted among SOFV who completed a specific psychedelic clinical program in Mexico. Retrospective questions probed alcohol use and post-traumatic stress symptoms during the 30-days before and 30-days after the psychedelic treatment. A total of 65 SOFV completed treatment and were eligible for contact. Of these, 51 (78%) completed the survey, and 27 (42%) reported alcohol misuse (≥4 on the AUDIT-C) in the 30 days prior to treatment and were included in analyses (Mean Age = 40; male = 96%; Caucasian/White = 96%).ResultsThere were significant and very large reductions in retrospective reports of alcohol use (P< 0.001;d= –2.4) and post-traumatic stress symptoms (P< 0.001;d= –2.8) and a significant and large increase in psychological flexibility (P< 0.001;d= –1.8), from before-to-after the psychedelic treatment. In the 30 days after treatment, 85% reduced their alcohol consumption to non-risky levels (33% abstinent; 52% non-risky drinking). Increases in psychological flexibility were strongly associated with reductions in alcohol use and post-traumatic stress symptoms (rs range 0.38–0.90; ps < 0.05).ConclusionRigorous longitudinal studies should be conducted to determine whether psychedelic-assisted therapy holds promise as an intervention in this population.

OBJECTIVE: Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT. METHODS: To explore these unexpected differences in genetic correlations, the authors conducted the first item-level and the largest GWAS of AUDIT items (N=160,824) and applied a multivariate framework to mitigate previous biases. RESULTS: The authors identified novel patterns of similarity (and dissimilarity) among the AUDIT items and found evidence of a correlated two-factor structure at the genetic level ("consumption" and "problems," rg=0.80). Moreover, by applying empirically derived weights to each of the AUDIT items, the authors constructed an aggregate measure of alcohol consumption that was strongly associated with alcohol dependence (rg=0.67), moderately associated with several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, the authors identified novel genetic associations between alcohol consumption, alcohol misuse, and health. CONCLUSIONS: This work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

Interscalene brachial plexus block is the standard regional analgesic technique for shoulder surgery. Given its adverse effects, alternative techniques have been explored. Reports suggest that the erector spinae plane block may potentially provide effective analgesia following shoulder surgery. However, its analgesic efficacy for shoulder surgery compared with placebo or local anaesthetic infiltration has never been established. We conducted a randomised controlled trial to compare the analgesic efficacy of pre-operative T2 erector spinae plane block with peri-articular infiltration at the end of surgery. Sixty-two patients undergoing arthroscopic shoulder repair were randomly assigned to receive active erector spinae plane block with saline peri-articular injection (n = 31) or active peri-articular injection with saline erector spinae plane block (n = 31) in a blinded double-dummy design. Primary outcome was resting pain score in recovery. Secondary outcomes included pain scores with movement; opioid use; patient satisfaction; adverse effects in hospital; and outcomes at 24 h and 1 month. There was no difference in pain scores in recovery, with a median difference (95%CI) of 0.6 (-1.9-3.1), p = 0.65. Median postoperative oral morphine equivalent utilisation was significantly higher in the erector spinae plane group (21 mg vs. 12 mg; p = 0.028). Itching was observed in 10% of patients who received erector spinae plane block and there was no difference in the incidence of significant nausea and vomiting. Patient satisfaction scores, and pain scores and opioid use at 24 h were similar. At 1 month, six (peri-articular injection) and eight (erector spinae plane block) patients reported persistent pain. Erector spinae plane block was not superior to peri-articular injection for arthroscopic shoulder surgery.

Trauma exposure across the lifespan produces risks for posttraumatic stress disorder (PTSD), depression, anxiety, as well as global disability in functioning. This retrospective clinical chart review is the first of its kind to assess the utility of sublingual ketamine-assisted body-centered psychotherapy in trauma-exposed patients in a real world clinic setting. De-identified clinical records data on self-reported symptom measures were retrospectively analyzed for patients (N = 18; M age = 45.22, SD = 12.90) entering ketamine-assisted psychotherapy treatment in an outpatient clinic between 2018 and 2020. Patients who completed six sessions of ketamine therapy reported meaningful (e.g., medium effect size) improvements in PTSD symptoms (P = 0.058; d = −0.48) and global disability in functioning (P = 0.050; d = −0.52) and statistically significant and meaningful improvements in depression (P = 0.019; d = −0.53). There were no improvements in anxiety symptoms. Sublingual ketamine-assisted psychotherapy was associated with heterogenous clinical utility among patients with trauma-exposure in an outpatient setting. This study was underpowered and unrepresentative of the population of ketamine patients in the United States. Replication of these findings is needed with larger and more diverse patient samples.

Diagnoses of depression, anxiety, or other mental illness capture just one aspect of the psychosocial elements of the perinatal period. Perinatal loss; trauma; unstable, unsafe, or inhumane work environments; structural racism and gendered oppression in health care and society; and the lack of a social safety net threaten the overall well-being of birthing people, their families, and communities. Developing relevant policies for perinatal mental health thus requires attending to the intersecting effects of racism, poverty, lack of child care, inadequate postpartum support, and other structural violence on health. To fully understand and address this issue, we use a human rights framework to articulate how and why policy makers must take progressive action toward this goal. This commentary, written by an interdisciplinary and intergenerational team, employs personal and professional expertise to disrupt underlying assumptions about psychosocial aspects of the perinatal experience and reimagines a new way forward to facilitate well-being in the perinatal period.

We present a case in which a patient developed fever and leukocytosis subsequent to each monthly haloperidol decanoate injection, an adverse reaction that does not meet the diagnostic criteria of neuroleptic malignant syndrome (NMS) or any previously reported adverse reaction for this medication. A patient being treated with haloperidol decanoate for psychosis experienced a fever within 3 days of injection and leukocytosis along with swelling, pain, and a “knot” feeling at the injection site. This recurred after each injection for several months. Muscle rigidity or changes in vital signs other than temperature were not noted. Temperature and injection site reactions resolved with administration of acetaminophen and ibuprofen. The elevation in temperature was discovered as a result of universal twice daily temperature monitoring implemented due to the COVID-19 pandemic. Reports of fever with antipsychotics are typically associated with NMS or heat stroke; the details of this case do not meet the clinical criteria for either. Similar reactions are reported for other antipsychotics, such as clozapine and olanzapine, but not for haloperidol. The recommendation was to discontinue use of the medication due to an unclear mechanism of the reaction.

Previous studies suggest that musicians may be at higher risk for a set of medical problems; however, this literature has been limited by relatively small sample sizes, self-reports, and lack of controls. To address such limitations, we examined trends in the medical care of musicians in an Electronic Health Record database. On the basis of a collection of keywords and regular expressions in the patients' clinical notes, we identified 9803 "musicians" that we matched for sex, median age (across the medical record), ethnicity, race, the length of record, and the number of visits with 49,015 controls. We fitted 1263 logistic regression models to determine whether the phenotype was correlated with musicianship. Two hundred fifty-seven phenotypes were more prevalent in musicians than controls after Bonferroni adjustment (P < 7.6 × 10-6 ), including diseases of the larynx and vocal cords (OR = 2.32 (95% CI: 2.25-2.40)), and hearing loss (OR = 1.36 (95% CI: 1.32-1.39)). Fifteen phenotypes were significantly more prevalent in controls than musicians, including coronary atherosclerosis (OR = 0.91 (95% CI: 0.89-0.94)). Although being a musician was related to many occupational health problems, we identified protective effects of musicianship in which certain disorders were less common in musicians than in controls, indicating that active musical engagement could have health benefits analogous to athletic engagement.

Purpose The COVID-19 pandemic has had a profound impact on American life. However, the burden of the pandemic has not been distributed equally. The purpose of this study was to investigate whether racial and economic residential segregation were associated with COVID-19 related factors in the nation's capital, Washington D.C., during the first year of the pandemic. Methods Racial, economic, and racialized economic segregation were assessed using the Index of Concentration at the Extremes measure and data from the 2014–2018 American Community Survey. COVID-19 related factors (i.e., incidence, testing rate, and percent positivity) were assessed using data from the Washington D.C. government. Spearman rank correlation was used to assess the relationship between each segregation measure and each COVID-19 related factor. Results Washington D.C. neighborhoods with a higher concentration of African Americans, lower income residents, and African Americans with low income had a higher incidence of COVID-19 and greater percent positivity, but lower testing rates compared to their counterparts. Conclusions There is a geographic mismatch between neighborhoods most vulnerable to COVID-19 and the neighborhoods where the testing resources are being used. More resources should be allocated to the most vulnerable neighborhoods to address the COVID-19 pandemic in an equitable manner.

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well.

University human research ethics application procedures can be complicated and daunting, especially for international students unfamiliar with the process and the language. We conducted focus groups and interviews with four research higher degree and 21 Master’s coursework international students at an Australian university to gain their views on the human ethics application process. We found the most important influences on their experience were: the time it took to do an application; support from supervisors, peers and others; their own language skills; and their lack of familiarity with research ethics procedures. To improve the experience of international students undertaking research involving human research ethics applications, we recommend universities provide guidance on institutional ethics review processes, concepts and terminology, with translations in a range of languages, together with guidance on how to conduct research ethically within and outside the students’ own countries. We also recommend curricula be developed to further students’ understanding of the importance of ethical research practice, and that these curricula be embedded in undergraduate and postgraduate degree programs and reflected in course learning outcomes.

Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P0.05 was considered to be statistically significant.A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Purpose We examined if childhood socioeconomic status (SES) was related to adult leucocyte telomere length (TL) using the data of 361 African American (AA) participants from the GENE-FORECAST Study. We also assessed the mediating role of behavioral and psychosocial factors in the association between childhood SES and adult TL. Methods Childhood SES was assessed individually by using participant’s mother’s education and occupation, father’s education and occupation, parental home ownership, and family structure. TL was assessed using the quantitative polymerase chain reaction method. Information on potential confounders and mediators were collected. The associations of childhood SES with TL were assessed using multivariable linear regression models. We used path analysis to quantify and test the share of these associations that was statistically explained by each of the mediators (participant’s educational attainment, smoking status, physical activity, dietary habit, perceived stress, and depressive symptoms). Results Mother’s education was associated with longer average TL (β: 0.021; 95% CI: 0.001, 0.04, p=0.038) in confounder adjusted models. Once mediators were introduced in the model, the estimates were reduced and remained marginally significant (β: 0.017; 95% CI: −0.003, 0.038, p=0.061). According to path model, approximately 19% of the effect of mother’s education on TL (β: 0.004; 95% CI: −0.001, 0.01, p < 0.10) was mediated through participant’s own education level. No significant mediation effect was observed for any other mediators. Conclusions These data provide evidence that participant’s mother’s education was positively linked to adult TL in AA population. Participant’s own educational level partially explained this association.

OBJECTIVE To identify risk factors and generate hypotheses for pediatric persistent postconcussion symptoms (PPCS). SETTING A regional healthcare system in the Southeastern United States. PARTICIPANTS An electronic health record-based algorithm was developed and validated to identify PPCS cases and controls from an institutional database of more than 2.8 million patients. PPCS cases (n = 274) were patients aged 5 to 18 years with PPCS-related diagnostic codes or with PPCS key words identified by natural language processing of clinical notes. Age, sex, and year of index event-matched controls (n = 1096) were patients with mild traumatic brain injury codes only. Patients with moderate or severe traumatic brain injury were excluded. All patients used our healthcare system at least 3 times 180 days before their injury. DESIGN Case-control study. MAIN MEASURES The outcome was algorithmic classification of PPCS. Exposures were all preinjury medical diagnoses assigned at least 180 days before the injury. RESULTS Cases and controls both had a mean of more than 9 years of healthcare system use preinjury. Of 221 preinjury medical diagnoses, headache disorder was associated with PPCS after accounting for multiple testing (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.6-5.0; P = 2.1e-4). Six diagnoses were associated with PPCS at a suggestive threshold for statistical significance (false discovery rate P < .10): gastritis/duodenitis (OR = 2.8; 95% CI: 1.6-5.1; P = 5.0e-4), sleep disorders (OR = 2.3; 95% CI: 1.4-3.7; P = 7.4e-4), abdominal pain (OR = 1.6; 95% CI: 1.2-2.2; P = 9.2e-4), chronic sinusitis (OR = 2.8; 95% CI: 1.5-5.2; P = 1.3e-3), congenital anomalies of the skin (OR = 2.9; 95% CI: 1.5-5.5; P = 1.9e-3), and chronic pharyngitis/nasopharyngitis (OR = 2.4; 95% CI: 1.4-4.3; P = 2.5e-3). CONCLUSIONS These results support the strong association of preinjury headache disorders with PPCS. An association of PPCS with prior gastritis/duodenitis, sinusitis, and pharyngitis/nasopharyngitis suggests a role for chronic inflammation in PPCS pathophysiology and risk, although results could equally be attributable to a higher likelihood of somatization among PPCS cases. Identified risk factors should be investigated further and potentially considered during the management of pediatric mild traumatic brain injury cases.

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics., Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Background Preeclampsia is a major pregnancy complication associated with long-term maternal cardiometabolic disease. Research generally is focused on metabolic and pathophysiological changes during pregnancy; however, there is much less focus on the early postpartum period in subjects who suffered preeclampsia. The aim of this study was to (1) characterize energy intake and expenditure 6 months following normotensive and preeclamptic pregnancies and (2) examine associations between energy balance, body composition, insulin resistance measures (HOMA-IR), and clinical characteristics. Design A cross-sectional study 6 months following normotensive (n = 75) and preeclamptic (n = 22) pregnancies was performed. Metabolic measurements included anthropometrics measures, body composition via bioelectrical impedance analysis, 24-h energy expenditure via SenseWear Armbands, energy intake via a 3-day food diary, and serum metabolic parameters. Results Six months following preeclampsia, women had a significantly higher weight (77.3 ± 20.9 kg vs 64.5 ± 11.4 kg, P = 0.01), fat mass percentage (FM%; 40.7 ± 7.4% vs 34.9 ± 8.1%, P = 0.004), and insulin resistance (HOMA-IR 2.2 ± 1.5 vs 1.0 ± 0.7, P = 0.003), as well as reduced HDL levels (1.5 ± 0.4 mmol/L vs 1.8 ± 0.4 mmol/L, P = 0.01) compared to normotensive women. Women post-preeclampsia had lower activity-related energy expenditure (P = 0.02) but a decreased total energy intake (P = 0.02), leading to a more negative energy balance compared to their normotensive counterparts (−1942 kJ/24 h vs −480 kJ/24 h, P = 0.02). Conclusion Increases in insulin resistance and FM%, reduced high-density lipoprotein, and more sedentary lifestyles characterize the postpartum period following preeclamptic compared with normotensive pregnancies. Early post-preeclampsia interventions, such as lifestyle behavior change, should be implemented and assessed to determine whether they reduce long-term cardiometabolic risk in women who experienced preeclampsia during pregnancy.

To minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease (COVID-19), the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend wearing face masks in public. Some have expressed concern that these may affect the cardiopulmonary system by increasing the work of breathing, altering pulmonary gas exchange and increasing dyspnea, especially during physical activity. These concerns have been derived largely from studies evaluating devices intentionally designed to severely affect respiratory mechanics and gas exchange. We review the literature on the effects of various face masks and respirators on the respiratory system during physical activity using data from several models: cloth face coverings and surgical masks, N95 respirators, industrial respirators, and applied highly resistive or high–dead space respiratory loads. Overall, the available data suggest that although dyspnea may be increased and alter perceived effort with activity, the effects on work of breathing, blood gases, and other physiological parameters imposed by face masks during physical activity are small, often too small to be detected, even during very heavy exercise. There is no current evidence to support sex-based or age-based differences in the physiological responses to exercise while wearing a face mask. Although the available data suggest that negative effects of using cloth or surgical face masks during physical activity in healthy individuals are negligible and unlikely to impact exercise tolerance significantly, for some individuals with severe cardiopulmonary disease, any added resistance and/or minor changes in blood gases may evoke considerably more dyspnea and, thus, affect exercise capacity.

The European intelligence space is reaching a new level of maturity because of an increasingly consolidated transgovernmental network of intelligence professionals. What explains the change in this key security network, especially given the challenges inherent in intelligence sharing? The overall strengthening of the European transgovernmental intelligence network is a product of both informal, bottom-up networking and formal, top-down policies to enhance intelligence sharing. Yet, it is clear that the informal side is of utmost importance given the difficulties inherent in trusting outsiders with valuable information. It is through informality that the transgovernmental network shares best practices and knowhow, strengthening the backbone of the European intelligence space. At the same time, there is a realm of intelligence sharing that is still subject to deep secrecy, the dynamics of which are very difficult to truly know. As a result, there is a disjuncture between expert-level intelligence sharing and community governance practices.

OBJECTIVE This study examined the feasibility and comparison of two styles of yoga within the context of a standard behavioral weight-loss intervention (SBWI). METHODS Fifty adults with obesity (BMI: 31.3 ± 3.8 kg/m2 ) participated in this 6-month study that included a SBWI and a calorie- and fat-reduced diet. Randomization was to restorative Hatha (SBWI+RES) or Vinyasa (SBWI+VIN) yoga. Yoga was prescribed to increase from 20 to 40 to 60 minutes per session across the intervention. Weight was assessed at baseline and 6 months. Perceptions of yoga were assessed at the completion of the intervention. RESULTS Adjusted weight loss was -3.4 kg (95% CI: -6.4 to -0.5) in SBWI+RES and -3.8 kg (95% CI: -6.8 to -0.9) in SBWI+VIN (P

Obtaining measured synthetic aperture radar (SAR) data for training automatic target recognition (ATR) models can be too expensive (in terms of time and money) and complex of a process in many situations. In response, researchers have developed methods for creating synthetic SAR data for targets using electro-magnetic prediction software, which is then used to enrich an existing measured training dataset. However, this approach relies on the availability of some amount of measured data. In this work, we focus on the case of having 100% synthetic training data, while testing on only measured data. We use the SAMPLE dataset public released by AFRL, and find significant challenges to learning generalizable representations from the synthetic data due to distributional differences between the two modalities and extremely limited training sample quantities. Using deep learning-based ATR models, we propose data augmentation, model construction, loss function choices, and ensembling techniques to enhance the representation learned from the synthetic data, and ultimately achieved over 95% accuracy on the SAMPLE dataset. We then analyze the functionality of our ATR models using saliency and feature-space investigations and find them to learn a more cohesive representation of the measured and synthetic data. Finally, we evaluate the out-of-library detection performance of our synthetic-only models and find that they are nearly 10% more effective than baseline methods at identifying measured test samples that do not belong to the training class set. Overall, our techniques and their compositions significantly enhance the feasibility of using ATR models trained exclusively on synthetic data.

Background: African Americans (AA) are disproportionally affected by cardiovascular disease as compared to other racial-ethnic groups. Exposure to adverse socioeconomic conditions may partially explain disparities in risk factors and prevalence and cardiovascular diseases for AA. We aim to study the impact of poverty status on metabolic syndrome (MetS) and its components among African Americans. Methods: We used data from the National Health and Nutritional Examination Survey (NHANES) cycles 2001-2006. We defined MetS using the Joint Scientific Definition as the presence of any 3/5 components: elevated blood pressure (BP), elevated triglycerides (TGL), lower high-density lipoprotein cholesterol (LDL), elevated fasting plasma glucose (FPG), and elevated waist circumference (WC). Poverty to income ratio (PIR) was categorized as below poverty ( 3) groups. We used multivariable survey-weighted logistic regression models to study the impact of poverty status of prevalence of MetS and its components among AA men and women. Results: Overall, the average aggregate prevalence of MetS among AA sample was 22% in our study with prevalence being 25% for women and 18% among men (p 3) (OR = 1.57, 95%CI = 1.00 - 2.46, p = 0.05) with no association observed among men (OR (PIR = 1) = 0.70, 95%CI = 0.43 - 1.19, p = 0.13). Further, similar associations were observed for individual components among women including: elevated waist circumference (OR = 2.04, 95%CI = 1.37, 3.01, p 3). No association of poverty status with MetS and its components were observed among AA men. Clustering of factors identified key groups that define MetS among women included WC. Conclusion: African American women living below poverty have a higher likelihood of having MetS and 4 of 5 individual components. Clustering of these factors differ across men and women and should be further explored as tools for clinical management. Main Points: 1) Metabolic syndrome remains an important public health burden among African Americans and shows disparities by socioeconomic status; 2) Women living below poverty were more likely to have MetS and associated components as compared to women living above poverty; 3) Clustering of components gave us snapshot of factors that should be considered to develop gender specific targeted health interventions for MetS among African Americans.

Identifying psychosocial variables associated with physical activity may lead to the development of interventions that better address the challenges to participating in physical activity experienced by postbariatric surgery patients.To examine associations between select psychosocial variables and physical activity in patients who had undergone bariatric surgery within the past 2 years.Bariatric surgery candidates were recruited from the Greater Pittsburgh region.Eighty-three patients who had undergone bariatric surgery self-reported current physical activity and select psychosocial constructs. In addition, participants provided retrospective information on physical activity and psychosocial constructs before surgery.Patients increased physical activity from baseline (median = 156.00 [25th, 75th percentiles: 53.00, 600.00] kcal/week) to post surgery (median = 976.00 [25th, 75th percentiles: 344.00, 1832.00] kcal/week) (P.001). A number of pre- to postsurgery changes in psychosocial variables were associated with change in physical activity; however, only change in fitness orientation (P = .001), change in social support from friends (P = .005), and change in self-reported weight (P = .012) emerged as predictors of change in physical activity from pre- to postsurgery. Several postsurgery psychosocial factors were also significantly associated with postsurgery physical activity, but only postsurgery fitness orientation (P.001), social support from co-workers (P = .002), and physical function (P = .023) emerged as predictive of the amount of postsurgical PA.Pre- and postbariatric surgery interventions aimed at increasing physical activity participation may need to target important constructs that include the encouragement of social support and strategies to enhance the effort individuals put forward to engage in physical activity, as well as a focus on enhancing physical function and awareness of weight status.

This study examined how psychedelics reduced symptoms of racial trauma among black, indigenous, and people of color (BIPOC) subsequent to an experience of racism. A cross-sectional internet-based survey included questions about experiences with racism, mental health symptoms, and acute and enduring psychedelic effects. Changes in mental health were assessed by retrospective report of symptoms in the 30 days before and 30 days after an experience with psilocybin, Lysergic acid diethylamide (LSD), or 3,4-Methylenedioxymethamphetamine (MDMA). We recruited 313 diverse BIPOC in the US and Canada. Results revealed a significant (p < .001) and moderate (d = -.45) reduction in traumatic stress symptoms from before-to-after the psychedelic experience. Similarly, participants reported decreases in depression (p < .001; d = -.52), anxiety (p < .001; d = -.53), and stress (p < .001; d = -.32). There was also a significant relationship (Rc = 0.52, p < .001) between the dimension of acute psychedelic effects (mystical-type, insight, and challenging experiences) and decreases in a cluster of subsequent psychopathology (traumatic stress, depression, anxiety, and stress), while controlling for the frequency of prior discrimination and the time since the psychedelic experience. BIPOC have been underrepresented in psychedelic studies. Psychedelics may decrease the negative impact of racial trauma. Future studies should examine the efficacy of psychedelic-assisted therapy for individuals with a history of race-based trauma.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Organic photovoltaic cells promise cheap, flexible and scalable solar energy. Whereas light directly generates free charges in silicon photovoltaic cells, bound electron and hole pairs known as excitons are understood to be the primary excitations in organic semiconductors due to their low dielectric constants. These excitons must then be split apart at molecular heterojunctions in order to extract current. Recent record efficiency organic photovoltaics utilise the small molecule, Y6, as a key component in the photon-absorbing blend layer. This molecule and its analogues – unlike previous organic semiconductors – have both low band-gaps and high dielectric constants. Here we show that, in a neat film of Y6, these factors lead to intrinsic free charge generation without the need for a molecular heterojunction to split the exciton. We use a suite of intensity-dependent optical spectroscopy measurements to show that a significant (20-90%) fraction of free charges exist in equilibrium with bound states at light intensity equivalent to 1 sun. Rapid bimolecular charge recombination constrains single component Y6 organic photovoltaic devices to low efficiencies, but this recombination is reduced by the introduction of small quantities of donor polymer. Quantum-chemical calculations reveal charge generation pathways through strong coupling between exciton and CT states, and an intermolecular polarisation pattern that drives exciton dissociation. Our results challenge the understanding of how current record efficiency organic photovoltaics operate, and point towards new future possibilities – offering a molecular picture of intrinsic charge generation as a platform to improve charge yields, and renewing the possibility of efficient single-component organic photovoltaic devices.

Objectives Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. Study design Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. Main outcome measures Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. Secondary outcomes: maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. Conclusions BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.

The present study was designed to examine the effects of neonatal genistein exposure on measures of reproductive physiology and behavior. Approximately 24 h after birth, female and male Long-Evans rat pups were injected daily with genistein (150 µg, subcutaneous; n = 29) or olive oil (n = 23) between postnatal days 1 and 5. After weaning, we examined all subjects daily until they reached puberty (i.e. vaginal opening in female rats and preputial separation in male rats). For all female subjects, we also examined vaginal cytology. After monitoring estrous cyclicity, the female subjects were given the opportunity to interact with a gonadally intact male or a sexually receptive female rat on the day of behavioral estrus to assess sexual motivation (i.e. partner-preference test with and without physical contact), which has never been evaluated before. For all male subjects, we assessed the development of copulatory behavior and sexual motivation (partner-preference test without physical contact). Consistent with previous findings, we found that neonatal exposure to genistein did not affect puberty onset in female or male rats. However, female rats exposed to genistein displayed significantly more irregular estrous cycles than controls. Neonatal genistein exposure also altered the development of male copulatory behavior, as indicated by an increase in mount frequency and intromission frequency and shorter interintromission intervals. We extended previous findings confirming that neither female nor male sexual motivation was affected by neonatal genistein. The results of the present study have important implications for the development of reproductive physiology and behavior in human neonates exposed to genistein in soy-based baby formula.

Context Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, yet current diagnostic criteria are ineffective at identifying patients whose symptoms reside outside strict diagnostic criteria. As a result, PCOS is underdiagnosed and its etiology is poorly understood. Objective We aim to characterize the phenotypic spectrum of PCOS clinical features within and across racial and ethnic groups. Methods We developed a strictly defined PCOS algorithm (PCOSkeyword-strict) using the International Classification of Diseases, ninth and tenth revisions and keywords mined from clinical notes in electronic health records (EHRs) data. We then systematically relaxed the inclusion criteria to evaluate the change in epidemiological and genetic associations resulting in 3 subsequent algorithms (PCOScoded-broad, PCOScoded-strict, and PCOSkeyword-broad). We evaluated the performance of each phenotyping approach and characterized prominent clinical features observed in racially and ethnically diverse PCOS patients. Results The best performance came from the PCOScoded-strict algorithm, with a positive predictive value of 98%. Individuals classified as cases by this algorithm had significantly higher body mass index (BMI), insulin levels, free testosterone values, and genetic risk scores for PCOS, compared to controls. Median BMI was higher in African American females with PCOS compared to White and Hispanic females with PCOS. Conclusions PCOS symptoms are observed across a severity spectrum that parallels the continuous genetic liability to PCOS in the general population. Racial and ethnic group differences exist in PCOS symptomology and metabolic health across different phenotyping strategies.

Purpose Data mining algorithms using electronic health records (EHRs) are useful in large-scale population-wide studies to classify etiology and comorbidities ( Casey et al., 2016 ). Here, we apply this approach to developmental language disorder (DLD), a prevalent communication disorder whose risk factors and epidemiology remain largely undiscovered. Method We first created a reliable system for manually identifying DLD in EHRs based on speech-language pathologist (SLP) diagnostic expertise. We then developed and validated an automated algorithmic procedure, called, Automated Phenotyping Tool for identifying DLD cases in health systems data (APT-DLD), that classifies a DLD status for patients within EHRs on the basis of ICD (International Statistical Classification of Diseases and Related Health Problems) codes. APT-DLD was validated in a discovery sample ( N = 973) using expert SLP manual phenotype coding as a gold-standard comparison and then applied and further validated in a replication sample of N = 13,652 EHRs. Results In the discovery sample, the APT-DLD algorithm correctly classified 98% (concordance) of DLD cases in concordance with manually coded records in the training set, indicating that APT-DLD successfully mimics a comprehensive chart review. The output of APT-DLD was also validated in relation to independently conducted SLP clinician coding in a subset of records, with a positive predictive value of 95% of cases correctly classified as DLD. We also applied APT-DLD to the replication sample, where it achieved a positive predictive value of 90% in relation to SLP clinician classification of DLD. Conclusions APT-DLD is a reliable, valid, and scalable tool for identifying DLD cohorts in EHRs. This new method has promising public health implications for future large-scale epidemiological investigations of DLD and may inform EHR data mining algorithms for other communication disorders. Supplemental Material https://doi.org/10.23641/asha.12753578

Cesium lead halide perovskite nanocrystals exhibit high photoluminescence quantum efficiencies and tunability across the visible spectrum. This makes these crystals ideal candidates for solar panels, light-emitting diodes, lasers, and especially nanolasers. Due to the versatility of cation substitution in perovskite nanocrystals, they can be grown on amine-functionalized silicon dioxide nanoparticles, where the amine linker replaces the standard cation structure. Selectively growing luminescent nanocrystals on spherical silicon dioxide microspheres results in the opportunity to populate whispering-gallery modes in these spherical silica microspheres. In this case, the nanocrystal halide composition can be used to selectively tune the emission wavelength mode, and microsphere radius to tune the mode spacing. This silicon dioxide attachment also adds to the overall stability of the system. Through photoluminescence microscopy measurements, we show whispering gallery modes in individual perovskite-coated microspheres for CsPbBr

Objective:Natural recovery and treatment outcome studies published over the past four decades indicate that some individuals with substance use problems moderate their consumption of alcohol and ot...

Aims Elevated serum immunoglobulins have been associated with experimental and human hypertension for decades but whether immunoglobulins and B cells play a causal role in hypertension pathology is unclear. In this study, we sought to determine the role of B cells and high-affinity class-switched immunoglobulins on hypertension and hypertensive end-organ damage to determine if they might represent viable therapeutic targets for this disease. Methods and results We purified serum IgG from mice exposed to vehicle or angiotensin (Ang) II to induce hypertension and adoptively transferred these to wild type (WT) recipient mice receiving a subpressor dose of Ang II. We found that transfer of IgG from hypertensive animals leads does not affect blood pressure, endothelial function, renal inflammation, albuminuria, or T cell derived cytokine production compared with transfer of IgG from vehicle infused animals. As an alternative approach to investigate the role of high affinity, class-switched immunoglobulins, we studied mice with genetic deletion of activation-induced deaminase (Aicda-/-). These mice have elevated levels of IgM but virtual absence of class-switched immunoglobulins such as IgG subclasses and IgA. Neither male nor female Aicda-/- mice were protected from Ang II-induced hypertension and renal/vascular damage. To determine if IgM or non-immunoglobulin dependent innate functions of B cells play a role in hypertension, we studied mice with severe global B cell deficiency due to deletion of the membrane exon of the IgM heavy chain (μMT-/-). μMT-/- mice were also not protected from hypertension or end-organ damage induced by Ang II infusion or deoxycorticosterone acetate (DOCA)-salt treatment. Conclusions These results suggest that B cells and serum immunoglobulins do not play a causal role in hypertension pathology. Translational perspective Our results suggest that in most cases of essential hypertension, B cells are not a causal factor in the pathophysiology of disease. Thus, elevated serum immunoglobulins seen in hypertensive animals and humans may reflect a biomarker of aberrant immune activation in hypertension and not a therapeutic target. However, autoantibodies may cause hypertension in special cases, and more work is needed to determine whether specific B cell subsets might play an important role that is masked by global B cell deficiency.

Aim To report an analysis of ~1 year of setmelanotide treatment for obesity and hunger, as well as metabolic and cardiac outcomes, in individuals with Bardet‐Biedl syndrome (BBS). Materials and methods Individuals aged 12 years and older with BBS received once‐daily setmelanotide. The dose was titrated every 2 weeks to establish the individual therapeutic dose (≤3 mg); treatment continued for an additional 10 weeks. Participants who lost 5 kg or more (or ≥5% of body weight if

This research is concerned with the development of a realistic model for e-procurement adoption by organizations and groups observing the Rules of Islamic Sharia (RIS). This model is intended to be based on the behavioural control, subjective norms, and the recognition of the benefits and risks of eprocurement adoption. The developed model, “E-Procurement Adoption Model” (E-PAM), combined and extended two existing models previously used for information technology adoption. Central to the design of the E-PAM is the principle that a realistic model should consider all relevant psychological, social, cultural, demography, and religious factors. The mediating components “mediators” that determine the final model are thus determined by the specific aforementioned factors about of on to the development of an e-procurement approach in the context of the Rules of Islamic Sharia. Therefore, in the design of the research model, factors including perceived usefulness, perceived ease of use, organizational facilitators, organisational leadership, critical success factors, challenges, barriers, and benefits were taken into account. These factors in turn gave rise to the two mediating components of ‘Attitude’ and ‘Rules of Islamic Sharia’.Several hypotheses were made in order to establish links between the contributing factors, the mediators, and the adoption of e-procurement as the final dependent variable output of the model. An online questionnaire survey was conducted to validate the hypotheses using a structural equation model. The descriptive analysis of the survey data provided demographic details of the questionnaire participants and their employers and statistical analysis methods were used to correlate the contributing factors and mediators. The analysis of the survey data confirmed the existence of positive relationships between Benefits and the Rules of Islamic Sharia, organizational Facilitators and the Adoption of e-procurement, Organisational Facilitators, and Organisational Leadership, and Rules of Islamic Sharia and the Adoption of e-procurement. It was observed that Perceived Usefulness and Organisational Leadership do not influence the adoption of e-procurement. Furthermore, the analysis suggested that Rules of Islamic Sharia is not influenced by Critical Success Factors. This model successfully validated most of the initial hypotheses made regarding e-procurement adoption. The results of this research strongly encourage organisations observing Rules of Islamic Sharia to adopt e-procurement practices.

Background: This paper describes the impact evaluation of a large big data platform initiative that is being undertaken in order to increase the probability of its success. The initiative, MIDAS (Meaningful Integration of Data Analytics and Services), is a European health-based Horizon 2020 project comprising a consortium of members from various universities, research institutions, and government agencies. Objectives: The purpose of the paper is to present a pioneering platform that will support healthcare policymakers in their decision-making by enabling greater and more efficient use of their data. The goal is to present and evaluate the results of the MIDAS project across four countries. Methods/Approach: The literature is replete with examples of worthwhile technology projects that have failed due to user resistance. In order to avoid such failure, and ensure the success of the final MIDAS platform, a detailed impact evaluation is being undertaken at timed periods of development. Results: This paper describes the impact evaluation process, outlining the use of Q-methodology and the development of a 36-item concourse using the HTMLQ system for that purpose. Conclusions: This research contributes to the overall understanding of how impact evaluation can be undertaken at timed periods during the development of an innovative technology for organisational purposes.

Supplementation of folic acid (FA) is beneficial to several neurological diseases because it promotes notch signaling and neurogenesis and reduces blood homocysteine levels. We hypothesized that postischemic supplementation of FA is beneficial for neuronal survival and regeneration. The objective of the present study was to determine the postischemic neuroprotective and neuroregenerative efficacy of FA supplementation and its effects on various cellular processes in vitro. This work benefited from the use of FA and glucose-free media to better assess the ischemic neuroprotection provided by FA supplementation. The postischemic supplementation of FA significantly improved cell viability, and the improvement was primarily by obstructing the oxygen-glucose deprivation (OGD)-activated apoptosis. Furthermore, postischemic treatment with FA significantly reduced the mitochondrial membrane depolarization and the formation of acidic organelles triggered by OGD. Moreover, FA's effect on neuroregeneration following OGD was evaluated by measuring the cell proliferation and neurite outgrowth length. Treatment with FA enhanced cell proliferation and neurite outgrowth significantly. Thus, these results revealed some of the mechanisms by which FA supplementation provided neuroprotection and neuroregeneration following ischemic injury and highlighted the need for further research into the potential of folic acid as a clinical drug for ischemic stroke.

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (–0.2%) in the placebo group ( P =0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus –9±193 [–0.9%] mL/min, P =0.012), ventilatory equivalents of carbon dioxide (–0.8 versus –0.06, P =0.014), and work rate (+3.8 versus +0.34 W, P =0.021). There was no an improvement in myocardial performance index (–0.02 vs 0.01, P =0.030), but no change in reactive hyperemia index, or serum brain-type natriuretic peptide level. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02741115.

International audience; In this update, we focus on selected topics of high clinical relevance for health care providers who treat patients with heart failure (HF), on the basis of clinical trials published after 2017. Our objective was to review the evidence, and provide recommendations and practical tips regarding the management of candidates for the following HF therapies: (1) transcatheter mitral valve repair in HF with reduced ejection fraction; (2) a novel treatment for transthyretin amyloidosis or transthyretin cardiac amyloidosis; (3) angiotensin receptor-neprilysin inhibition in patients with HF and preserved ejection fraction (HFpEF); and (4) sodium glucose cotransport inhibitors for the prevention and treatment of HF in patients with and without type 2 diabetes. We emphasize the roles of optimal guideline-directed medical therapy and of multidisciplinary teams when considering transcatheter mitral valve repair, to ensure excellent evaluation and care of those patients. In the presence of suggestive clinical indices, health care providers should consider the possibility of cardiac amyloidosis and proceed with proper investigation. Tafamidis is the first agent shown in a prospective study to alter outcomes in patients with transthyretin cardiac amyloidosis. Patient subgroups with HFpEF might benefit from use of sacubitril/valsartan, however, further data are needed to clarify the effect of this therapy in patients with HFpEF. Sodium glucose cotransport inhibitors reduce the risk of incident HF, HF-related hospitalizations, and cardiovascular death in patients with type 2 diabetes and cardiovascular disease. A large clinical trial recently showed that dapagliflozin provides significant outcome benefits in well treated patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤ 40%), with or without type 2 diabetes.

Context As many as 75% of patients with polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice. Objective Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment. Design, Patients, and Methods Leveraging the electronic health records (EHRs) of 124 852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS). We evaluated its predictive capability across different ancestries and perform a PRS-based phenome-wide association study (PheWAS) to assess the phenomic expression of the heightened risk of PCOS. Results The integrated polygenic prediction improved the average performance (pseudo-R2) for PCOS detection by 0.228 (61.5-fold), 0.224 (58.8-fold), 0.211 (57.0-fold) over the null model across European, African, and multi-ancestry participants respectively. The subsequent PRS-powered PheWAS identified a high level of shared biology between PCOS and a range of metabolic and endocrine outcomes, especially with obesity and diabetes: “morbid obesity”, “type 2 diabetes”, “hypercholesterolemia”, “disorders of lipid metabolism”, “hypertension”, and “sleep apnea” reaching phenome-wide significance. Conclusions Our study has expanded the methodological utility of PRS in patient stratification and risk prediction, especially in a multifactorial condition like PCOS, across different genetic origins. By utilizing the individual genome–phenome data available from the EHR, our approach also demonstrates that polygenic prediction by PRS can provide valuable opportunities to discover the pleiotropic phenomic network associated with PCOS pathogenesis.

In both basic and applied studies, quantification of herbivory on foliage is a key metric in characterizing plant-herbivore interactions, which underpin many ecological, evolutionary, and agricultural processes. Current methods of quantifying herbivory are slow or inaccurate. We present LeafByte, a free iOS application for measuring leaf area and herbivory. LeafByte can save data automatically, read and record barcodes, handle both light and dark colored plant tissue, and be used non-destructively.We evaluate its accuracy and efficiency relative to existing herbivory assessment tools.LeafByte has the same accuracy as ImageJ, the field standard, but is 50% faster. Other tools, such as BioLeaf and grid quantification, are quick and accurate, but limited in the information they can provide. Visual estimation is quickest, but it only provides a coarse measure of leaf damage and tends to overestimate herbivory.LeafByte is a quick and accurate means of measuring leaf area and herbivory, making it a useful tool for research in fields such as ecology, entomology, agronomy, and plant science.

Anthracycline agents are commonly used in early breast cancer but are associated with dose-related cardiotoxicity. Diastolic dysfunction may be more common and occur earlier than systolic dysfunction ([1][1],[2][2]). Eplerenone is an oral mineralocorticoid antagonist (MRA); these agents prevent

Background Malignancy is one of the known leading causes of death among long-term liver transplantation (LT) survivors. Pancreatic cancer has an incidence of 7.6/100,000 in North America and constitutes a diagnostic challenge post-LT. Methods This is a single-center, retrospective review of the electronic health records (EHRs) of LT recipients with pancreatic adenocarcinoma (1990-2019). The prevalence of pancreatic adenocarcinoma in our institutional non-LT population was assessed using an institutional de-identified database (Synthetic Derivative). Results Six out of 2,232 (0.27%) LT recipients were diagnosed with pancreatic adenocarcinoma. Median age at diagnosis was 66.0 years (IQR, 57.8-71.8 years). Median time from LT to pancreatic adenocarcinoma diagnosis was 8.9 years (IQR, 4.7-16.2 years), the median size on imaging was 3.2 cm (IQR, 3.1-4.7 cm), and all tumors were located on the head of the pancreas. Three patients underwent surgical resection (one with adjuvant chemotherapy), two underwent palliative care, and one palliative chemotherapy with gemcitabine and abraxane. Over a median follow-up of 220.5 days (IQR, 144.8-399.5 days), all six patients died due to disease progression (100%). Pancreatic adenocarcinoma was diagnosed in 5,033 out of 2,484,772 (0.20%) individuals in the Synthetic Derivative. Conclusions Our findings identified an increased incidence of pancreatic adenocarcinoma following LT compared to the general population.

BackgroundElectronic health records (EHR) are useful tools for understanding complex medical phenotypes, but they have been underutilized for opioid use disorders (OUD). Patterns of prescription opioid use might provide an objective measure of OUD risk.MethodsWe extracted data for over 2.6 million patients across three health registries (Vanderbilt University Medical Center, Mass General Brigham, Geisinger) between 2005 and 2018. We defined three groups based on levels of opioid exposure: No Prescription, Minimal Exposure (2 prescriptions within 90 days at least once, but never 3 prescriptions ResultsThe prevalence of substance (alcohol, tobacco, cannabis) use disorders was higher in patients with OUD and Chronic Exposure than those with No Prescription or Minimal Exposure. Patients in the OUD and Chronic Exposure groups had more psychiatric (anxiety, depression, schizophrenia, bipolar disorder) and medical comorbidities (pain, hepatitis C, HIV) than those in the Minimal Exposure group. Notably, patients in the Minimal Exposure group had different comorbidity profiles (higher rates of substance use and psychiatric disorders, more pain conditions) than those in the Unscreened or No Prescription groups, highlighting the value of including opioid exposure in studies of OUD.ConclusionsLong-term opioid prescription use may serve as an additional tool to characterize OUD risk.

Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.

BackgroundSleep problems are common in individuals with autism spectrum disorder (ASD). This study reviews one detailed approach to querying the electronic health record (EHR).MethodsWe developed methods for identifying individuals with ASD and defined their sleep problems using International Classification of Diseases (ICD) codes or key words. We examined treatment responses to melatonin.ResultsSleep problems were documented in 86% of patients and using specific keywords yielded more sleep diagnoses than ICD codes alone. About two-thirds of patients benefitted from melatonin.ConclusionsOur study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in ASD. Using specific keywords could be helpful in future work that queries the EHR.

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.

Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this disorder.

Rupert Jones,1– 3 Andrew Davis,1,2 Brooklyn Stanley,1,2 Steven Julious,4 Dermot Ryan,5 David J Jackson,6 David MG Halpin,7 Katherine Hickman,8 Hilary Pinnock,9 Jennifer K Quint,10 Kamlesh Khunti,11 Liam G Heaney,12 Phillip Oliver,4 Salman Siddiqui,13 Ian Pavord,14 David HM Jones,15 Michael Hyland,3,16 Lewis Ritchie,17 Pam Young,18 Tony Megaw,18 Steve Davis,19 Samantha Walker,20 Stephen Holgate,21 Sue Beecroft,22 Anu Kemppinen,1,2 Francis Appiagyei,1,2 Emma-Jane Roberts,1,2 Megan Preston,1,2 Antony Hardjojo,1,2 Victoria Carter,1,2 Marije van Melle,1,2 David Price1,2,17 1Optimum Patient Care, Cambridge, UK; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3Faculty of Health, University of Plymouth, Plymouth, UK; 4University of Sheffield, South Yorkshire, UK; 5Usher Institute, University of Edinburgh, Edinburgh, UK; 6Guy’s & St Thomas’ NHS Trust, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 8Bradford and Leeds Clinical Commissioning Group, Leeds, UK; 9Asthma UK Centre for Applied Research, Usher Institute, The University of Edinburgh, Edinburgh, UK; 10National Heart & Lung Institute, Imperial College London, London, UK; 11Diabetes Research Centre, University of Leicester, Leicester, UK; 12Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 13Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, UK; 14Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 15Box Surgery, Wiltshire, UK; 16Plymouth Marjon University, Plymouth, UK; 17Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 18Wellbeing Software, Mansfield, UK; 19Interface Clinical Services, Leeds, UK; 20Asthma UK & British Lung Foundation, London, UK; 21Clinical and Experimental Sciences, University of Southampton, Southampton, UK; 22OPEN Health, Buckinghamshire, UKCorrespondence: David PriceAcademic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 3105 1489Email dprice@opri.sgIntroduction: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care.Methods: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18– 85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥ 4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration.Results: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥ 40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05– 2.17]), female sex (adjOR=1.37 [1.02– 1.85]), frailty (adjOR=2.39 [1.29– 4.27]), visit to A&E (adjOR=4.28 [2.31– 7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77– 5.79]). Aches and pain (adjOR=1.70 [1.21– 2.39]), appetite loss (adjOR=3.15 [1.78– 5.92]), confusion and disorientation (adjOR=2.17 [1.57– 2.99]), diarrhea (adjOR=1.4 [1.03– 1.89]), and persistent dry cough (adjOR=2.77 [1.94– 3.98]) were symptom features statistically more common in long COVID.Conclusion: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.Keywords: SARS-CoV-2, questionnaire, observational study, frailty, chronic diseases

ObjectivesSARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination.MethodsWe recruited 16 subjects with COVID-19 infection an average of 7 months previously and 15 subjects before and 2 weeks after Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Pre-pandemic plasma, saliva and basal tears from 11 individuals were included as healthy controls. Antibody responses to 5 SARS-CoV-2 antigens were measured via multiplex.ResultsIgG antibodies to Spike and Nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison to uninfected controls. While RBD-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. In contrast, high levels of IgG antibodies to Spike and RBD, but not Nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination, but were unchanged in tears and saliva.ConclusionBoth infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests neutralising antibodies may be low in the tears late following infection.

Inflammation increases the risk of cardiometabolic disease. Delineating specific inflammatory pathways and biomarkers of their activity could identify the mechanistic underpinnings of the increased risk. Plasma levels of kynurenine, a metabolite involved in inflammation, associates with cardiometabolic disease risk. We used genetic approaches to identify inflammatory mechanisms associated with kynurenine variability and their relationship to cardiometabolic disease. We identified single-nucleotide polymorphisms (SNPs) previously associated with plasma kynurenine, including a missense-variant (rs3184504) in the inflammatory gene SH2B3/LNK. We examined the association between rs3184504 and plasma kynurenine in independent human samples, and measured kynurenine levels in SH2B3-knock-out mice and during human LPS-evoked endotoxemia. We conducted phenome scanning to identify clinical phenotypes associated with each kynurenine-related SNP and with a kynurenine polygenic score using the UK-Biobank (n = 456,422), BioVU (n = 62,303), and Electronic Medical Records and Genetics (n = 32,324) databases. The SH2B3 missense variant associated with plasma kynurenine levels and SH2B3−/− mice had significant tissue-specific differences in kynurenine levels.LPS, an acute inflammatory stimulus, increased plasma kynurenine in humans. Mendelian randomization showed increased waist-circumference, a marker of central obesity, associated with increased kynurenine, and increased kynurenine associated with C-reactive protein (CRP). We found 30 diagnoses associated (FDR q SH2B3 variant, but not with SNPs mapping to genes known to regulate tryptophan-kynurenine metabolism. Plasma kynurenine may be a biomarker of acute and chronic inflammation involving the SH2B3 pathways. Its regulation lies upstream of CRP, suggesting that kynurenine may be a biomarker of one inflammatory mechanism contributing to increased cardiometabolic disease risk.