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Abstract Prevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers that recognize specific cell types within a tissue. Such aptamers could potentially improve the development of drugs for several diseases, including neuromuscular disorders, by targeting solely the proteins involved in their pathogenesis. Here, we describe our attempt to utilize in vivo SELEX with a modification in the methodology that drives the selection of intravenously injected aptamers towards a specific cell type of interest. Our data suggest that the incorporation of a cell enrichment step can direct the in vivo localization of RNA aptamers into cardiomyocytes, the cardiac muscle cells, more readily over other cardiac cells. Given the crucial role of cardiomyocytes in the disease pathology in DMD cardiomyopathy and therapy, these aptamers hold great potential as drug delivery vehicles with cardiomyocyte selectivity.

Increasing evidence suggests that the “NACHT-LRR and PYD domain-containing protein 3” (NLRP3) inflammasome plays an important role in atherosclerotic cardiovascular disease (ASCVD). Recent preclinical evidence has suggested that the NLRP3 inflammasome may play a prominent role in the pathogenesis of atrial fibrillation (AF). As such, the therapies that have shown efficacy in reducing ASCVD events may also prove beneficial in AF. In this article, we review the findings that implicate the NLRP3 inflammasome in the pathogenesis of AF, discuss existing evidence behind the use of anti-inflammatory agents for AF, and discuss the future role that colchicine and other anti-inflammatory agents may play in the prevention and treatment of AF.

The quantum Hall effect can be used to study the physics of correlated systems and can reveal different features of the associated phase transitions. Here, the authors consider mass anisotropy and the impact on the phase transitions of quantum Hall charge density wave states in a 2D electron gas.

Abstract Advances in immune checkpoint therapy and targeted therapy have led to improvement in overall survival for patients with advanced melanoma. Single agent checkpoint PD-1 blockade and combination with BRAF/MEK targeted therapy demonstrated benefit in overall survival (OS). Superior response rates have been demonstrated with combined PD-1/CTLA-4 blockade, with a significant OS benefit compared with single-agent PD-1 blockade. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to therapy remain real challenges in melanoma. Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers but they have yet to be fully characterized and implemented clinically. Overall, the progress in melanoma therapeutics and translational research will help to optimize treatment regimens to overcome resistance and develop robust biomarkers to guide clinical decision-making. During the Melanoma Bridge meeting (December 3rd–5th, 2020, Italy) we reviewed the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine.

Abstract Background Smartphone addiction, as with other behavioral addictions, is associated with social, physical, and mental health issues. In this article, we investigated the prevalence of smartphone addiction among postgraduate students and evaluated its correlation with social demographics, depression, attention-deficit/hyperactivity disorder (ADHD), and nicotine dependence. Objectives The objective of this study was to investigate the prevalence of smartphone addiction among Middle Eastern postgraduate students, determine the factors associated with smartphone addiction, and estimate the incidence rate of major depressive disorder (MDD), ADHD, insomnia, and nicotine addiction among postgraduate students with smartphone addiction. Methods As part of a cross-sectional online survey, participants were given a self-questionnaire divided into six sections: Socio-demographics, Smartphone Addiction Scale (SAS), Patient Health Questionnaire (PHQ9) for Depression, Athens Insomnia Scale (AIS), the Fagerström Test for Cigarette Dependence Questionnaire (FTCd), and the adult ADHD Self-Report Scale (ASRS-v1.1). Results Of the 506 patients, 51.0% of the participants demonstrated smartphone addiction. A significant association was also observed between extensive smartphone use and MDD (P = 0.001). Of the smokers in this study, 41.5% were addicted to smartphones (P = 0.039). Smartphone addicts had approximately two times the chance of having insomnia (OR = 2.113) (P = 0.013). In addition, they showcased more ADHD symptoms (OR = 2.712) (P

Objective: To evaluate interest in coronary artery calcium (CAC) among the general public during the past 17 years and to compare trends with real-world data on number of CAC procedures performed. Methods: We used Google Trends, a publicly available database, to access search query data in a systematic and quantitative fashion to search for CAC-related key terms. Search terms included calcium test, heart score, calcium score, coronary calcium, and calcium test score. We accessed Google Trends in January 2021 and analyzed data from 2004 to 2020. Results: From 2004 to December 31, 2020, CAC-related search interest (in relative search volume) increased continually worldwide (+201.9%) and in the United States (+354.8%). Three main events strongly influenced search interest in CAC: reports of a CAC scan of the president of the United States led to a transient 10-fold increase in early January 2018. American College of Cardiology/American Heart Association guideline release led to a sustained increase, and lockdown after the global pandemic due to COVID-19 led to a transient decrease. Real-world data on performed CAC scans showed an increase between 2006 and 2017 (+200.0%); during the same time period, relative search volume for CAC-related search terms increased in a similar pattern (+70.6%-1511.1%). For the search term coronary calcium scan near me, a potential representative of active online search for CAC scanning, we found a +28.8% increase in 2020 compared with 2017. Conclusion: Google Trends, a valuable tool for assessing public interest in health-related topics, suggests increased overall interest in CAC during the last 17 years that mirrors real-world usage data. Increased interest is seemingly linked to reports of CAC testing in world leaders and endorsement in major guidelines.

Background and Aims: We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM). Methods: To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at 50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM. Condensed abstract: This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.

A core principle of the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Chest Pain Guideline is the importance of preventive therapies among patients with nonobstructive or obstructive coronary artery disease (CAD). Accordingly, this editorial provides unique insights that emphasize the role of preventive cardiology throughout the new guideline. For the first time, CAD was defined to also include nonobstructive plaque. This definition was based on the fact that individuals who have nonobstructive plaque are at an increased risk of atherosclerotic events compared with those who do not. Herein, we highlight guideline recommendations related to the diagnosis and management of nonobstructive CAD. We also highlight recommendations which emphasize the importance of preventive therapies. Adoption of these recommendations have the potential to lead to enhanced preventive therapies and improve patient outcomes.

Ketamine is a versatile medication with an emerging role for the treatment of numerous psychiatric conditions, including treatment resistant depression. Current psychiatry guidelines for its intravenous administration to treat depression recommend regular blood pressure monitoring and an aggressive approach to potential transient hypertensive episodes induced by ketamine infusions. While this approach is aimed at ensuring patient safety, it should be updated to align with best practice guidelines in the management of hypertension. This review defines and summarizes the currently recommended approach to the hypertensive emergency, the asymptomatic hypertensive urgency, and discusses their relevance to intravenous ketamine therapy. With an updated protocol informed by these best practice guidelines, ketamine treatment for depression may be more accessible to facilitate psychiatric treatment.

BackgroundWith the rise of fragility, conflict and violence (FCV), understanding the prevalence and risk factors associated with mental disorders is beneficial to direct aid to vulnerable groups. To better understand mental disorders depending on the population and the timeframe, we performed a systematic review to investigate the aggregate prevalence of depression, anxiety and post-traumatic stress symptoms among both civilian and military population exposed to war.MethodsWe used MEDLINE (PubMed), Web of Science, PsycINFO, and Embase to identify studies published from inception or 1–Jan, 1945 (whichever earlier), to 31–May, 2022, to reporting on the prevalence of depression, anxiety and post-traumatic stress symptoms using structured clinical interviews and validated questionnaires as well as variables known to be associated with prevalence to perform meta-regression. We then used random-effects bivariate meta-analysis models to estimate the aggregate prevalence rate.ResultsThe aggregate prevalence of depression, anxiety and post-traumatic stress during times of conflict or war were 28.9, 30.7, and 23.5%, respectively. Our results indicate a significant difference in the levels of depression and anxiety, but not post-traumatic stress, between the civilian group and the military group respectively (depression 34.7 vs 21.1%, p < 0.001; anxiety 38.6 vs 16.2%, p < 0.001; post-traumatic stress: 25.7 vs 21.3%, p = 0.256). The aggregate prevalence of depression during the wars was 38.7% (95% CI: 30.0–48.3, I2 = 98.1%), while the aggregate prevalence of depression post-wars was 29.1% (95% CI: 24.7–33.9, I2 = 99.2%). The aggregate prevalence of anxiety during the wars was 43.4% (95% CI: 27.5–60.7, I2 = 98.6%), while the aggregate prevalence of anxiety post-wars was 30.3% (95% CI: 24.5–36.9, I2 = 99.2%). The subgroup analysis showed significant difference in prevalence of depression, and anxiety between the civilians and military group (p < 0.001).ConclusionThe aggregate prevalence of depression, anxiety and post-traumatic stress in populations experiencing FCV are 28.9, 30.7, and 23.5%, respectively. There is a significant difference in prevalence of depression and anxiety between civilians and the military personnels. Our results show that there is a significant difference in the prevalence of depression and anxiety among individuals in areas affected by FCV during the wars compared to after the wars. Overall, these results highlight that mental health in times of conflict is a public health issue that cannot be ignored, and that appropriate aid made available to at risk populations can reduce the prevalence of psychiatric symptoms during time of FCV.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337486, Identifier 337486.

Objective To perform a systematic and meta-analysis on the prevalence rates of mental health symptoms including anxiety and depression during the COVID-19 pandemic in the general population in Eastern Europe, as well as three select sub-populations: students, general healthcare workers, and frontline healthcare workers. Data sources Studies in PubMed, Embase, Web of Science, PsycINFO, and medRxiv up to 6 February 2021. Eligibility criteria and data analysis Prevalence rates of mental health symptoms in the general population and key sub-populations during the COVID-19 pandemic in Eastern Europe. Data were pooled using a random-effects meta-analysis to estimate the prevalence rates of anxiety and depression. Results The meta-analysis identifies and includes 21 studies and 26 independent samples in Eastern Europe. Poland (n = 4), Serbia (n = 4), Russia (n = 3), and Croatia (n = 3) had the greatest number of studies. To our knowledge, no studies have been conducted in eleven Eastern European countries including Hungary, Slovakia, and Slovenia. The pooled prevalence of anxiety in 18 studies with 22 samples was 30% (95% CI: 24–37%) pooled prevalence of depression in 18 studies with 23 samples was 27% (95% CI: 21–34%). Implications The cumulative evidence from the meta-analysis reveals high prevalence rates of clinically significant symptoms during the COVID-19 pandemic in Eastern Europe. The findings suggest evidence of a potential mental health crisis in Eastern Europe during the ongoing COVID-19 pandemic. Our synthesis also reveals a relative lack of studies in certain Eastern European countries as well as high heterogeneities among the existing studies, calling for more effort to achieve evidence-based mental healthcare in Eastern Europe.

Abstract The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.

Background: This study aimed to compare the severity of psychological impact, anxiety and depression between people from two developing countries, Iran and China, and to correlate mental health parameters with variables relating to the COVID-19 pandemic. Although China and Iran are developing countries based on the World Bank’s criteria, these two countries are different in access to resources and health care systems. We hypothesized that Iranians would show higher levels of depression, anxiety and stress as compared to Chinese. Methods: This study collected information related to the COVID-19 pandemic including physical health, precautionary measures and knowledge about the pandemic. We also used validated questionnaires such as the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21) to assess the mental health status. Results: There were a total of 1411 respondents (550 from Iran; 861 from China). The mean IES-R scores of respondents from both countries were above the cut-off for post-traumatic stress disorder (PTSD) symptoms. Iranians had significantly higher levels of anxiety and depression (p < 0.01). Significantly more Iranians believed COVID-19 was transmitted via contact, practised hand hygiene, were unsatisfied with health information and expressed less confidence in their doctors, but were less likely to wear a facemask (p < 0.001). Significantly more Iranians received health information related to COVID-19 via television while Chinese preferred the Internet (p < 0.001). Conclusions: This cross-country study found that Iranians had significantly higher levels of anxiety and depression as compared to Chinese. The difference in reported measures between respondents from Iran and China were due to differences in access to healthcare services and governments’ responses to the pandemic.

Abstract Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Abstract Studies conducted in primary care as well as in psychiatric settings show that more than half of patients suffering from major depressive disorder (MDD) have poor adherence to antidepressants. Patients prematurely discontinue antidepressant therapy for various reasons, including patient-related (e.g., misperceptions about antidepressants, side-effects, and lack of tolerability), clinician-related (e.g., insufficient instruction received by clinicians about the medication, lack of shared decision-making, and follow-up care), as well as structural factors (e.g., access, cost, and stigma). The high rate of poor adherence to antidepressant treatments provides the impetus for identifying factors that are contributing to noncompliance in an individual patient, to implement a careful education about this phenomenon. As adherence to antidepressants is one of the major unmet needs in MDD treatment, being associated with negative outcomes, we sought to identify a series of priorities to be discussed with persons with MDD with the larger aim to improve treatment adherence. To do so, we analyzed a series of epidemiological findings and clinical reasons for this phenomenon, and then proceeded to define through a multi-step consensus a set of recommendations to be provided by psychiatrists and other practitioners at the time of the first (prescription) visit with patients. Herein, we report the results of this initiative.

Abstract The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including sequential or combination treatment are being tested. Approaches to overcome resistance and to potentiate the immune response are being developed. Increasing evidence emerges that tissue and blood-based biomarkers can predict the response to a therapy. The latest findings in melanoma research, including insights into the tumor microenvironment and new biomarkers, improved understanding of tumor immune response and resistance, novel approaches for combination strategies and the role of neoadjuvant and adjuvant therapy, were the focus of discussions at the Melanoma Bridge meeting (5–7 December, 2019, Naples, Italy), which are summarized in this report.

EHBP1 is an adaptor protein that regulates vesicular trafficking and links endosomes to the actin cytoskeleton. Here, authors show that both termini of EHBP1 have membrane targeting potential and that in the absence of its binding partner Rab8, the bMERB and CH domain of EHBP1 form an intramolecular complex which auto-inhibits actin binding.

Abstract This study demonstrates significant differences between the area of complete spatial summation (Ricco’s area, RA) in eyes with and without non-pathological, axial myopia. Contrast thresholds were measured for six stimuli (0.01–2.07 deg2) presented at 10º eccentricity in 24 myopic subjects and 20 age-similar non-myopic controls, with RA estimated using iterative two-phase regression analysis. To explore the effects of axial length-induced variations in retinal image size (RIS) on the measurement of RA, refractive error was separately corrected with (i) trial lenses at the anterior focal point (near constant inter-participant RIS in mm), and (ii) contact lenses (RIS changed with axial length). For spectacle corrected measurements, RA was significantly larger in the myopic group, with a significant positive correlation also being observed between RA and measures of co-localised peripheral ocular length. With contact lens correction, there was no significant difference in RA between the groups and no relationship with peripheral ocular length. The results suggest RA changes with axial elongation in myopia to compensate for reduced retinal ganglion cell density. Furthermore, as these changes are only observed when axial length induced variations in RIS are accounted for, they may reflect a functional adaptation of the axially-myopic visual system to an enlarged RIS.

Abstract Aim This review will identify, evaluate and synthesize the literature related to evidence‐based design of healthcare environments and to identify impacts of the built environment on the outcomes and experiences of patients, significant others and staff. Design A mixed‐method systematic review of literature 2010–2018. Methods Database searches for evidence in peer‐reviewed journals will be conducted electronically using CINAHL, Medline, SCOPUS and Web of Science. Abstract, full‐text screening and data extraction will be completed independently by the reviewers. Quality assessment will follow Swedish Agency for Health Technology Assessment and Social Services Assessment. Results This review will offer knowledge for informed decisions about the design of the healthcare environment. The review is comprehensive, includes a large volume of literature various research designs and will highlight the knowledge gap in evidence‐based design and provide a breadth of knowledge about the built environments and its impact on health and well‐being.

Abstract Background Heart failure (HF) represents an accumulated burden of systemic vascular damage and is the fastest growing form of cardiovascular disease (CVD). Due to increasing HF-attributable mortality rates, we sought to assess the association of the new 2019 Pooled Cohort equations to Prevent Heart Failure (PCP-HF) risk score with CVD and all-cause mortality. Methods We linked data for 6333 black and white men and women aged 40–79 years, whom underwent electrocardiographic examination from the Third National Health and Nutrition Exam Survey, to National Death Index record matches. Sex- and race-specific PCP-HF risk scores were calculated using data on age, smoking, body mass index, systolic blood pressure, total cholesterol, HDL-cholesterol, fasting blood glucose, QRS complex duration, and antihypertensive and/or glucose-lowering medications. Cox regression estimated hazard ratios for the association of the PCP-HF risk score with CVD and all-cause mortality. Results Individuals were on average 54.9 years old (51.7% women, 25.4% black) and the median 10-year HF risk was 1.6% (Q1 = 0.5, Q3 = 4.8). There were 3178 deaths, 1116 from CVD, over a median follow-up time of 22.3 years. Black women had a higher 10-year HF risk compared to white women (2.1% vs. 1.1%; p

Despite numerous advances in all areas of cardiovascular care, cardiovascular disease (CVD) is the leading cause of death in the United States (US). There is compelling evidence that interventions to improve diet are effective in cardiovascular disease prevention. This clinical practice statement emphasizes the importance of evidence-based dietary patterns in the prevention of atherosclerotic cardiovascular disease (ASCVD), and ASCVD risk factors, including hyperlipidemia, hypertension, diabetes, and obesity. A diet consisting predominantly of fruits, vegetables, legumes, nuts, seeds, plant protein and fatty fish is optimal for the prevention of ASCVD. Consuming more of these foods, while reducing consumption of foods with saturated fat, dietary cholesterol, salt, refined grain, and ultra-processed food intake are the common components of a healthful dietary pattern. Dietary recommendations for special populations including pediatrics, older persons, and nutrition and social determinants of health for ASCVD prevention are discussed.

Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996–1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018–2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34–2.47), CAC (aOR, 1.40; 95% CI, 1.08–1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07–1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06–1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05–1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Investigations into the pathogenetic mechanisms underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have provided significant insight into the disease. At the cellular level, ALS and FTD are classified as proteinopathies, which is motor neuron degeneration and death characterized by pathological protein aggregates or dysregulated proteostasis. At both the clinical and molecular level there are common signaling pathways dysregulated across the ALS and FTD spectrum (ALS/FTD). Sequestosome-1/p62 is a multifunctional scaffold protein with roles in several signaling pathways including proteostasis, protein degradation via the ubiquitin proteasome system and autophagy, the antioxidant response, inflammatory response, and apoptosis. Notably these pathways are dysregulated in ALS and FTD. Mutations in the functional domains of p62 provide links to the pathogenetic mechanisms of p62 and dyshomeostasis of p62 levels is noted in several types of ALS and FTD. We present here that the dysregulated ALS and FTD signaling pathways are linked, with p62 converging the molecular mechanisms. This review summarizes the current literature on the complex role of p62 in the pathogenesis across the ALS/FTD spectrum. The focus is on the underlying convergent molecular mechanisms of ALS and FTD-associated proteins and pathways that dysregulate p62 levels or are dysregulated by p62, with emphasis on how p62 is implicated across the ALS/FTD spectrum.

There is interest in the role of peripheral interleukin-6 (IL-6) in depression and the effect of treatment (e. g., pharmacologic, psychosocial, neurostimulation). However, the relationship between cognitive behavioral therapy (CBT), IL-6 and depression has not yet been established. We conducted a meta-analysis to explore the association between CBT and change of peripheral IL-6 levels in depressive symptoms or major depressive disorder (MDD). A systematic search of online databases (i.e., PubMed, Web of Science, Google Scholar, PsycINFO, and Cochrane Library) was completed from inception to May 2021. In total, 10 eligible papers with 940 participants reporting peripheral IL-6 levels before and after CBT were included in the analysis. The main result indicates that peripheral levels of IL-6 were significantly lower after CBT intervention in individuals with depression, with a small effect (SMD = 0.38, 95% CI: 0.07, 0.69, p = 0.02). The results of subgroup analyses demonstrate that (1) there was a significant decrease in IL-6 for studies that were equal to or

ObjectivePrior research has shown that ketamine has anti-suicide effects. Additional evidence also suggests that ketamine may offer pro-cognitive effects. Herein, we propose that the anti-suicide effects of ketamine are partially mediated via pro-cognitive effects. We aimed to determine whether improvement in cognitive function mediated change in suicidal ideation was associated with ketamine treatment.MethodsUnipolar or bipolar depressive patients (n = 86) with suicidal ideation received six infusions of ketamine (0.5 mg/kg) over 2 weeks. The current severity of suicidal ideation and depression symptoms were assessed with the Beck Scale for Suicide Ideation (SSI) and the Montgomery–Asberg Depression Rating Scale (MADRS), respectively, at baseline, days 13 and 26. Cognitive domains, including processing speed, working memory, visual learning, and verbal learning were measured with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery at the same time points.ResultsMediation analysis showed a significant total effect of ketamine treatment on SSI score (coef = –1.853, 95%CI [–2.2, –1.5]). The direct and total indirect (MADRS total score and any of cognitive domains) effects of ketamine on suicidal ideation both were statistically significant (direct: coef = –1.064 to –1.352; total indirect: coef = –0.501 to –0.788). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.ConclusionDepressive symptoms severity and processing speed performance partially mediated improvements in suicidal ideation after repeated ketamine infusions in persons with unipolar or bipolar depressive disorder.

Background Hepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary arteries. However, knowledge is limited on the role HGF may play in extracoronary calcification (ECC). This study examined whether HGF is associated with ECC in the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta and descending thoracic aortic (DTAC).Methods At baseline, adults aged 45–84 years, free of CVD, in the Multi-Ethnic Study of Atherosclerosis had HGF and ECC measured by ELISA and cardiac CT scan, respectively. ECC measurements were repeated after an average of 2.4 years of follow-up. Prevalent ECC was defined as Agatston score >0 at baseline. Incident ECC was defined as Agatston score >0 at follow-up among participants with Agatston score=0 at baseline. We used Poisson and linear mixed-effects regression models to estimate the association between HGF and ECC, adjusted for sociodemographic and CVD risk factors.Results Of 6648 participants, 53% were women. Mean (SD) age was 62 (10) years. Median (IQR) of HGF was 905 (757-1087) pg/mL. After adjustment for CVD risk factors, the highest HGF levels (tertile 3) were associated with greater prevalence and extent of AVC, MAC and DTAC at baseline compared with the lowest tertile (tertile 1). Additionally, the risk of incident AVC and MAC increased by 62% and 45%, respectively, in demographic-adjusted models. However, the associations were not statistically significant in fully adjusted models. The highest HGF levels were also associated with 10% and 13% increase in MAC and DTAC progression, respectively, even after adjustment for CVD risk factors.Conclusion Higher HGF levels were significantly associated with a greater risk of calcification at some extracoronary sites, suggesting an alternate biological pathway that could be targeted to reduce CVD risk.

Abstract Studies on herbal medicine have exposed some toxic effects on humans. Peperomia pellucida (L.) HBK (P. pellucida) is one of the herbal medicines recommended as an alternative to synthetic medicine for diseases. Studies exist on the pharmacological activities of P. pellucida extracts, but studies on the potential hepatotoxic and mutagenic effects of subchronic administration of P. pellucida aqueous extracts, which is very important knowledge when we venture into alternative medicine, are lacking. In this study, two concentrations (60 mg/kg and 30 mg/kg) of P. pellucida aqueous extracts — decoction and freeze-dried extracts —were administered in vivo to BALB/c mice for nine (9) weeks. Significant differences were observed between the 60 mg/kg freeze-dried extract and the control in terms of mice weight and micronucleus frequency at 7-8 weeks of treatment. Also, no significant differences were found between groups in serum transaminases levels. Generally, there is no sufficient evidence to show that subchronic exposure to P. pellucida aqueous extracts is hepatotoxic though 60 mg/kg concentration may be mutagenic. This study suggests that although the herbal medicine is safe for prolonged consumption, users are advised to take precautions and moderations of its use due to the possibility of potential mutagenic effects.

Summary: Background: Early diagnosis of major depressive disorder (MDD) could enable timely interventions and effective management which subsequently improve clinical outcomes. However, quantitative and objective assessment tools for the suspected cases who present with depressive symptoms have not been fully established. Methods: Based on a large-scale dataset (n = 363 subjects) collected with functional near-infrared spectroscopy (fNIRS) measurements during the verbal fluency task (VFT), this study proposed a data representation method for extracting spatiotemporal characteristics of NIRS signals, which emerged as candidate predictors in a two-phase machine learning framework to detect distinctive biomarkers for MDD. Supervised classifiers (e.g., support vector machine (SVM), k-nearest neighbors (KNN)) cooperated with cross-validation were implemented to evaluate the predictive capability of selected features in a training set. Another test set that was not involved in developing the algorithms enabled the independent assessment of the model's generalization. Findings: For the classification with the optimal fusion features, the SVM classifier achieved the highest accuracy of 75.6% ± 4.7% in the nested cross-validation, and the correct prediction rate of 78.0% with a sensitivity of 75.0% and a specificity of 81.4% in the test set. Moreover, the multiway ANOVA test on clinical and demographic factors confirmed that twenty out of 39 optimal features were significantly correlated with the MDD-distinctive consequence. Interpretation: The abnormal prefrontal activity of MDD may be quantified as diminished relative intensity and inappropriate activation timing of hemodynamic response, resulting in an objectively measurable biomarker for assessing cognitive deficits and screening MDD at the early stage. Funding: This study was funded by NUS iHeathtech Other Operating Expenses (R-722-000-004-731).

Abstract. An increasing number of studies have demonstrated the bidirectional hemostatic effect of selective serotonin reuptake inhibitors (SSRIs) on the risk of cerebrovascular and cardiovascular diseases. However, no previous study has focused on the relationship between SSRI and the risk of peripheral artery disease (PAD) in diabetes mellitus (DM). We sought to evaluate the association between SSRIs and the PAD risk in individuals with DM. We conducted a retrospective, population-based cohort study using data from the Longitudinal Health Insurance Database from 1999 to 2010 in Taiwan. A total of 5049 DM patients were included and divided into 2 groups: DM with SSRI users and DM with SSRI non-users. Propensity score matching and 1-year landmark analysis were used for our study design. Stratified Cox proportional hazard regressions were used to analyze the hazard ratio of the PAD risk in certain subgroups. DM with SSRI users did not affect the PAD risk compared to DM with SSRI non-users. These findings were consistent with all sensitivity analyses (i.e., age, sex, SSRI doses, antithrombotic medication use, and medical and psychiatric comorbidities). In this study, we found that there was no significant difference of PAD risk between DM with SSRI users and DM with SSRI non-users. DM with SSRI user did not affect PAD risk across any SSRI dose, age, sex, antithrombotic medications, and multiple comorbidities in the subgroup analysis.

Background Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP‐1RA use by cardiologists compared with other groups of clinicians. Methods and Results We conducted a descriptive analysis of serial, cross‐sectional data derived from IQVIA’s National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population‐level data, to estimate monthly SGLT2is and GLP‐1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association’s Physician Masterfile to calculate average annual SGLT2is and GLP‐1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP‐1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12‐fold for SGLT2is (from 2228 to 25 815) and 4‐fold for GLP‐1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP‐1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP‐1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP‐1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP‐1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions. Conclusions While use of SGLT2is and GLP‐1RAs by cardiologists in the United States increased substantially over a 6‐year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin‐3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996–1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin‐3 (≥75th sex‐specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin‐3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin‐3 (odds ratio [OR], 2.32; 95% CI, 1.88–2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5‐4‐fold higher risk of HF (HR, 4.19; 95% CI, 2.98–5.88) than those with normal weight and galectin‐3

BackgroundDepression is associated with significant morbidity and human capital costs globally. Early screening for depressive symptoms and timely depressive disorder case identification and intervention may improve health outcomes and cost-effectiveness among affected individuals. China’s public and academic communities have reached a consensus on the need to improve access to early screening, diagnosis, and treatment of depression. ObjectiveThis study aims to estimate the screening prevalence and associated factors of subthreshold depressive symptoms among Chinese residents enrolled in the cohort study using a mobile app–based integrated mental health care model and investigate the 12-month incidence rate and related factors of major depressive disorder (MDD) among those with subthreshold depressive symptoms. MethodsData were drawn from the Depression Cohort in China (DCC) study. A total of 4243 community residents aged 18 to 64 years living in Nanshan district, Shenzhen city, in Guangdong province, China, were encouraged to participate in the DCC study when visiting the participating primary health care centers, and 4066 (95.83%) residents who met the DCC study criteria were screened for subthreshold depressive symptoms using the Patient Health Questionnaire-9 at baseline. Of the 4066 screened residents, 3168 (77.91%) with subthreshold depressive symptoms were referred to hospitals to receive a psychiatric diagnosis of MDD within 12 months. Sleep duration, anxiety symptoms, well-being, insomnia symptoms, and resilience were also investigated. The diagnosis of MDD was provided by trained psychiatrists using the Mini-International Neuropsychiatric Interview. Univariate and multivariate logistic regression models were performed to explore the potential factors related to subthreshold depressive symptoms at baseline, and Cox proportional hazards models were performed to explore the potential factors related to incident MDD. ResultsAnxiety symptoms (adjusted odds ratio [AOR] 1.63, 95% CI 1.42-1.87) and insomnia symptoms (AOR 1.13, 95% CI 1.05-1.22) were associated with an increased risk of subthreshold depressive symptoms, whereas well-being (AOR 0.93, 95% CI 0.87-0.99) was negatively associated with depressive symptoms. During the follow-up period, the 12-month incidence rate of MDD among participants with subthreshold depressive symptoms was 5.97% (189/3168). After incorporating all significant variables from the univariate analyses, the multivariate Cox proportional hazards model reported that a history of comorbidities (adjusted hazard ratio [AHR] 1.49, 95% CI 1.04-2.14) and anxiety symptoms (AHR 1.13, 95% CI 1.09-1.17) were independently associated with an increased risk of incident MDD. The 5-item World Health Organization Well-Being Index was associated with a decreased risk of incident MDD (AHR 0.90, 95% CI 0.86-0.94). ConclusionsElevated anxiety symptoms and unfavorable general well-being were significantly associated with subthreshold depressive symptoms and incident MDD among Chinese residents in Shenzhen. Early screening for subthreshold depressive symptoms and related factors may be helpful for identifying populations at high risk of incident MDD.

BackgroundPrimary aldosteronism (PA) is the most common cause of secondary hypertension, and patients are at an increased risk of atrial fibrillation (AF) and stroke. We assessed the prevalence of PA in patients with recent stroke.MethodsWe recruited 300 patients admitted to an acute stroke unit with diagnosis of cerebrovascular accident (haemorrhagic/ischaemic) or transient ischaemic attack. Three months post-stroke, plasma renin and aldosterone were measured. Patients with an elevated aldosterone–renin ratio proceeded to the confirmatory saline loading test.ResultsTwenty-six of 192 (14%) patients had an elevated aldosterone–renin ratio. Three of 14 patients who proceeded to saline loading were confirmed with PA (post-saline aldosterone >138 pmol/l). Another three patients were classified as confirmed/likely PA based on the markedly elevated aldosterone–renin ratio and clinical characteristics. The overall prevalence of PA amongst stroke patients with hypertension was 4.0% (95% confidence interval (CI): 0.9%–7.1%). Prevalence of PA was higher amongst patients with cardioembolic stroke, 11% (95% CI: 1.3%–33%), resistant hypertension, 11% (95% CI: 0.3%–48%), and hypertension and AF, 30% (95%CI: 6.7%–65%). If only young patients or those with hypokalaemia were screened for PA, half of our patients with PA would not have been diagnosed. Our decision tree identified that stroke patients with AF and diastolic blood pressure ≥83mmHg were most likely to have PA.ConclusionWe found that amongst hypertensive patients with stroke, PA was more prevalent in those with AF, or cardioembolic stroke. Screening for PA should be considered for all patients with stroke.

Purpose: To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer.Methods: A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed.Results: The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both in vivo and in vitro results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68–0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61–0.75 for the two-year induction period).Conclusion: The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.

Background Aspirin is widely administered to prevent cardiovascular disease (CVD). However, appropriate use of aspirin depends on patient understanding of its risks, benefits, and indications, especially where aspirin is available over the counter (OTC). Methods and Results We did a survey of patient‐reported 10‐year cardiovascular risk; aspirin therapy status; form of aspirin access (OTC versus prescription); and knowledge of the risks, benefits, and role of aspirin in CVD prevention. Consecutive adults aged ≥50 years with ≥1 cardiovascular risk factor attending outpatient clinics in America and Europe were recruited. We also systematically reviewed national policies regulating access to low‐dose aspirin for CVD prevention. At each site, 150 responses were obtained (300 total). Mean±SD age was 65±10 years, 40% were women, and 41% were secondary prevention patients. More than half of the participants at both sites did not know (1) their own level of 10‐year CVD risk, (2) the expected magnitude of reduction in CVD risk with aspirin, or (3) aspirin’s bleeding risks. Only 62% of all participants reported that aspirin was routinely indicated for secondary prevention, whereas 47% believed it was routinely indicated for primary prevention (P=0.048). In America, 83.5% participants obtained aspirin OTC compared with 2.5% in Europe (P

Background: Alternatives to the Friedewald low-density lipoprotein cholesterol (LDL-C) equation have been proposed. Objective: To compare the accuracy of available LDL-C equations with ultracentrifugation measurement. Methods: We used the second harvest of the Very Large Database of Lipids (VLDbL), which is a population-representative convenience sample of adult and pediatric patients (N = 5,051,467) with clinical lipid measurements obtained via the vertical auto profile (VAP) ultracentrifugation method between October 1, 2015 and June 30, 2019. We performed a systematic literature review to identify available LDL-C equations and compared their accuracy according to guideline-based classification. We also compared the equations by their median error versus ultracentrifugation. We evaluated LDL-C equations overall and stratified by age, sex, fasting status, and triglyceride levels, as well as in patients with atherosclerotic cardiovascular disease, hypertension, diabetes, kidney disease, inflammation, and thyroid dysfunction. Results: Analyzing 23 identified LDL-C equations in 5,051,467 patients (mean±SD age, 56±16 years; 53.3% women), the Martin/Hopkins equation most accurately classified LDL-C to the correct category (89.6%), followed by the Sampson (86.3%), Chen (84.4%), Puavilai (84.1%), Delong (83.3%), and Friedewald (83.2%) equations. The other 17 equations were less accurate than Friedewald, with accuracy as low as 35.1%. The median error of equations ranged from –10.8 to 18.7 mg/dL, and was best optimized using the Martin/Hopkins equation (0.3, IQR–1.6 to 2.4 mg/dL). The Martin/Hopkins equation had the highest accuracy after stratifying by age, sex, fasting status, triglyceride levels, and clinical subgroups. In addition, one in five patients who had Friedewald LDL-C 70 mg/dL by the Martin/Hopkins equation. Conclusions: Most proposed alternatives to the Friedewald equation worsen LDL-C accuracy, and their use could introduce unintended disparities in clinical care. The Martin/Hopkins equation demonstrated the highest LDL-C accuracy overall and across subgroups.

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

Ketamine and esketamine (SPRAVATO) are rapid acting antidepressants that have gained evidence and popularity in recent years in treating depression, and are under investigation for other psychiatric indications. Ketamine is a potential drug of abuse and the addiction potential of these medications has been repeatedly cautioned in the psychiatric literature. However, no studies have included a systematic evaluation of addiction potential in their research so risk of this harm remains theoretically and has not been quantified to place in properly in a risk/benefit perspective. There is currently no easily accessible and ready to use tool for this purpose, which poses a barrier to including measures of addiction potential in ketamine and esketamine research. Based on review of the literature and a recently suggested comprehensive Ketamine Side Effect Tool (KSET), as well as the United States Food and Drug Administration recommendations for evaluation addictive potential of a drug, we created a simple, patient rated visual analog scale specifically for assessing ketamine/esketamine drug likeability, cravings and temptation to misuse. While this scale is not validated, in the absence of other accessible tools, use of this questionnaire would provide researchers and clinicians a simple and easy to use tool to begin monitoring addictive potential in patients taking ketamine or esketamine, and better inform future research, clinical practice and publicy policy regarding these substances.

BackgroundPain strongly coexists with depression. Ketamine has great analgesic and antidepressant effects, acting as a promising role in treating depression with pain. Few studies have evaluated impact of pain symptoms on antidepressant effect of ketamine infusions. Thus, present study investigated whether pain symptoms in individuals with depression moderate response to ketamine.MethodsOne hundred and four individuals with major depressive disorder and bipolar depression received six intravenous infusions of ketamine. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered at baseline, the next morning after each infusion and 2 weeks (Day 26) after the last infusion. Pain symptoms were collected at baseline using the short-form McGill Pain Questionnaire (SF-MPQ).ResultsThe prevalence of pain in patients with depression was 48.8%. Mix model analyses showed that pre-treatment pain symptoms assessed by each domain of SF-MPQ significantly moderated antidepressant response to six infusions of ketamine from baseline to day 26 (all p < 0.05). Then follow-up simple slopes analyses suggested that all patients across groups showed a significant symptomatic improvement after ketamine infusions (all p < 0.05), and patients with severe pain (across all domains of SF-MPQ) had greater improvement in depressive symptoms than those with mild pain or non-pain (all p < 0.05).ConclusionA significant and rapid improvement in depressive symptoms was observed in patients with depression and pain after ketamine treatment. Ketamine may be a novel and promising antidepressant preferentially for the therapy of depression with severe pain.

Background Suboptimal cardiovascular health (CVH) and social determinants of health (SDOH) have a significant impact on maternal morbidity and mortality. We aimed to evaluate the association of SDOH with suboptimal CVH among pregnant women in the United States. Methods and Results We examined cross‐sectional data of pregnant women aged 18 to 49 years from the National Health Interview Survey (2013–2017). We ascertained optimal and suboptimal CVH based on the presence of 0 to 1 and ≥2 risk factors (hypertension, diabetes, hyperlipidemia, current smoking, obesity, and insufficient physical activity), respectively. We calculated an aggregate SDOH score representing 38 variables from 6 domains (economic stability; neighborhood, physical environment, and social cohesion; community and social context; food; education; and healthcare system) and divided into quartiles. We used Poisson regression model to evaluate the association of SDOH with suboptimal CVH and risk factors. Our study included 1433 pregnant women (28.8±5.5 years, 13% non‐Hispanic Black). Overall, 38.4% (95% CI, 33.9–43.0) had suboptimal CVH versus 51.7% (95% CI, 47.0–56.3) among those in the fourth SDOH quartile. Risk ratios of suboptimal CVH, smoking, obesity, and insufficient physical activity were 2.05 (95% CI, 1.46–2.88), 8.37 (95% CI, 3.00–23.43), 1.54 (95% CI, 1.17–2.03), and 1.19 (95% CI, 1.01–1.42), respectively among those in the fourth SDOH quartile compared with the first quartile. Conclusions Over 50% of pregnant women with the highest SDOH burden had suboptimal CVH, highlighting the public health urgency for interventions in socially disadvantaged pregnant women with renewed strategies toward improving modifiable risk factors, especially smoking and insufficient physical activity.

Abstract Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous clinical entity, encompassing multiple different causes, and a cause of substantial morbidity and mortality. Current guidelines suggest a multimodality imaging approach in establishing the underlying cause for MINOCA, which is considered a working diagnosis. Recent studies have suggested that an initial workup consisting of cardiac magnetic resonance and invasive coronary imaging can yield the diagnosis in most patients. Cardiac magnetic resonance is particularly helpful in excluding nonischemic causes that can mimic MINOCA including myocarditis and Takotsubo cardiomyopathy, as well as for long‐term prognostication. Additionally, intracoronary imaging with intravascular ultrasound or optical coherence tomography may be warranted to evaluate plaque composition, or evaluate for plaque disruption or spontaneous coronary dissection. The role of noninvasive imaging modalities such as coronary computed tomography angiography is currently being investigated in the diagnostic approach and follow‐up of MINOCA and may be appropriate in lieu of invasive coronary angiography in select patients. In recent years, many strides have been made in the workup of MINOCA; however, significant knowledge gaps remain in the field, particularly in terms of treatment strategies. In this review, we summarize recent society guideline recommendations and consensus statements on the initial evaluation of MINOCA, review contemporary multimodality imaging approaches, and discuss treatment strategies including an ongoing clinical trial.

Desmoplastic small round cell tumor (DSRCT) is characterized by the t(11;22)(p13;q12) translocation, which fuses the transcriptional regulatory domain of EWSR1 with the DNA-binding domain of WT1, resulting in the oncogenic EWSR1-WT1 fusion protein. The paucity of DSRCT disease models has hampered preclinical therapeutic studies on this aggressive cancer. Here, we developed preclinical disease models and mined DSRCT expression profiles to identify genetic vulnerabilities that could be leveraged for new therapies. We describe four DSRCT cell lines and one patient-derived xenograft model. Transcriptomic, proteomic and biochemical profiling showed evidence of activation of the ERBB pathway. Ectopic expression of EWSR1-WT1 resulted in upregulation of ERRB family ligands. Treatment of DSRCT cell lines with ERBB ligands resulted in activation of EGFR, ERBB2, ERK1/2 and AKT, and stimulation of cell growth. Antagonizing EGFR function with shRNAs, small-molecule inhibitors (afatinib, neratinib) or an anti-EGFR antibody (cetuximab) inhibited proliferation of DSRCT cells. Finally, treatment of mice bearing DSRCT xenografts with a combination of cetuximab and afatinib significantly reduced tumor growth. These data provide a rationale for evaluating EGFR antagonists in patients with DSRCT. This article has an associated First Person interview with the joint first authors of the paper.

Background Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes. Methods and findings Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, pConclusion This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed.