ß-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

Prevalence and risks of tuberculosis multimorbidity in low-income and middle-income countries: a meta-review.

OBJECTIVES: Co-occurrence of tuberculosis (TB) with other chronic conditions (TB multimorbidity) increases complexity of management and adversely affects health outcomes. We aimed to map the prevalence of the co-occurrence of one or more chronic conditions in people with TB and associated health risks by systematically reviewing previously published systematic reviews. DESIGN: Systematic review of systematic reviews (meta-review). SETTING: Low-income and middle-income countries (LMICs). PAPERS: We searched in Medline, Embase, PsycINFO, Social Sciences Citation Index, Science Citation Index, Emerging Sources Citation Index and Conference Proceedings Citation Index, and the WHO Global Index Medicus from inception to 23 October 2020, contacted authors and reviewed reference lists. Pairs of independent reviewers screened titles, abstracts and full texts, extracted data and assessed the included reviews' quality (AMSTAR2). We included systematic reviews reporting data for people in LMICs with TB multimorbidity and synthesised them narratively. We excluded reviews focused on children or specific subgroups (eg, incarcerated people). PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence or risk of TB multimorbidity (primary); any measure of burden of disease (secondary). RESULTS: From the 7557 search results, 54 were included, representing >6 296 000 people with TB. We found that the most prevalent conditions in people with TB were depression (45.19%, 95% CI: 38.04% to 52.55%, 25 studies, 4903 participants, I2=96.28%, high quality), HIV (31.81%, 95% CI: 27.83% to 36.07%, 68 studies, 62 696 participants, I2=98%, high quality) and diabetes mellitus (17.7%, 95% CI: 15.1% to 20.0.5%, 48 studies, 48,036 participants, I2=98.3%, critically low quality). CONCLUSIONS: We identified several chronic conditions that co-occur in a significant proportion of people with TB. Although limited by varying quality and gaps in the literature, this first meta-review of TB multimorbidity highlights the magnitude of additional ill health burden due to chronic conditions on people with TB. PROSPERO REGISTRATION NUMBER: CRD42020209012.

Device-measured sedentary behaviour and anxiety symptoms during adolescence: a 6-year prospective cohort study.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents. METHODS: A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data. RESULTS: We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7-22.4), 12.1% (95% CI 3.4-20.1), and 14.7% (95% CI 4-24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses. CONCLUSION: Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Epicardial adipose tissue and adrenal gland volume in patients with borderline personality disorder.

Borderline personality disorder (BPD) is associated with an elevated mortality risk that is partially attributed to suicide, but few studies examined other possible causes of premature death. The present study compared epicardial adipose tissue (EAT) volume as a known early predictor of premature cardiovascular morbidity, cardiovascular risk indices, and adrenal gland volume (AGV) as an indicator for chronic hypothalamus-pituitary-adrenal (HPA) axis activation in females with borderline personality disorder (BPD), major depressive disorder (MDD) and in healthy individuals. Twenty-eight patients with BPD comorbid with MDD (BPD/MDD), 22 MDD patients and 26 healthy females (CTRL) of comparable age were included. EAT and AGV were assessed by magnetic resonance tomography; 10-year cardiovascular risk and diabetes risk were determined by PROCAM and FINDRISK score; metabolic syndrome was defined following National Cholesterol Education Adult Treatment Panel III R (NCEP/ATP III) criteria. MADRS was used to assess depression severity. After adjustment for age, body mass index (BMI), and physical activity, EAT and AGV were significantly increased in BPD/MDD compared to MDD and CTRL. EAT and AGV displayed a positive correlation. Finally, diabetes risk in BPD/MDD was elevated compared to CTRL and MDD. The present study highlights the increased cardiometabolic risk of BPD patients. We identify EAT accumulation as an early predictor and potential mediator of cardiovascular disease in BPD that appears to be driven at least in part by HPA axis dysregulation. Therefore, interventions that reduce EAT volume (i.e. exercise and diet) should be considered in the clinical management of BPD.

Association between physical activity and leisure-time sedentary behavior among 140,808 adolescents aged 12 to 15 from 47 low- and middle-income countries.

OBJECTIVES: Data from high-income countries (HICs) indicate that sedentary behavior is negatively associated with moderate-to-vigorous physical activity (MVPA) in young people. We examined associations between leisure-time sedentary behavior (LTSB) and MVPA in adolescents from 47 low- and middle-income countries (LMICs). STUDY DESIGN: Cross-sectional study. METHODS: Data from the Global school-based Student Health Survey were analyzed in 140,808 adolescents (13.8 ± 1.0 years; 49% girls). Time spent in LTSB was a composite variable assessing time spent sitting and playing computer games, watching TV, talking with friends during a typical day. The PACE + Adolescent Physical Activity Measure assessed MVPA levels. The association between ≥3 h/day of LTSB and adequate physical activity levels (every day last week 60 min MVPA) was explored with multivariable logistic regression analyses. RESULTS: The prevalence of ≥3 h/day of LTSB and 60 min of MVPA/day last week were 26.3% (girls 26.2%; boys 26.5%) and 15.3% (girls 12.1%; boys 18.4%), respectively. LTSB of ≥3 h/day versus <3 h/day was associated with a 35% increased odds for adequate levels of MVPA in boys [OR = 1.35 (95%CI = 1.23-1.48)] and 22% in girls [1.22 (95%CI = 1.10-1.36)]. CONCLUSIONS: Our data indicate that being physically active 60 min per day every day and at moderate-to-vigorous intensity and being sedentary ≥3 h/day during leisure-time might co-exist in adolescents in some LMICs.

Impact of replacing sedentary behaviour with other movement behaviours on depression and anxiety symptoms: a prospective cohort study in the UK Biobank.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods. METHODS: We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up. RESULTS: Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4-2.1%), 12.5% (95% CI, 11.4-13.5%), and 7.6% (95% CI, 6.9-8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94-0.96), 0.75 (95% CI, 0.74-0.76), and 0.90 (95% CI, 0.90-0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5-7.6%) and 4.5% (95% CI, 3.7-5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89-0.90) and 0.97 (95%CI, 0.96-0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7-5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06-1.08). CONCLUSIONS: Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity.

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses.

OBJECTIVE: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Metabolic syndrome and its components in people with intellectual disability: a meta-analysis.

BACKGROUND: People with intellectual disability have an increased risk for cardiovascular diseases and associated premature mortality. Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The aim of this meta-analysis was to describe the pooled prevalence of MetS and its components in people with intellectual disability taking into account variations in demographic, clinical and treatment-related variables. METHODS: Pubmed, Embase and CINAHL were searched until 5 August 2020 for studies reporting cross-sectional data on prevalences of MetS and its components in people with intellectual disability. Two independent reviewers extracted data. Random effects meta-analyses with subgroup and meta-regression analyses were employed. RESULTS: The pooled MetS prevalence after adjusting for publication bias was 22.5% [95% confidence interval (CI) = 16.8%-29.6%; N studies = 10; n participants = 2443, median age at study level = 38.5 years; 52% male]. Abdominal obesity was observed in 52.0% (95% CI = 42.0%-61.9%; I2  = 86.5; N = 5; n = 844), hypertension in 36.7% (95% CI = 26.1%-48.7%; N = 6; n = 926), hypertriglyceridaemia in 23.5% (95% CI = 18.8%-28.9%; N = 5; n = 845), low high-density-lipoprotein-cholesterol in 23.4% (95% CI = 19.3%-28.0%; N = 6; n = 917), and hyperglycaemia in 10.2% (95% CI = 7.6%-13.3%; N = 5; n = 845). Meta-regression revealed that a higher MetS frequency was moderated by older age (coefficient = 0.03; standard error = 0.01, 95% CI = 0.008 to 0.055; N = 19; n = 2443) and a higher proportion of people on antidepressants in the study (coefficient = 7.24; standard error = 0.90, 95% CI = 5.48-9.00; N = 4; n = 546). There were insufficient data comparing MetS in people with intellectual disability with age-matched and gender-matched controls. CONCLUSIONS: Considering that more than one fifth of people with intellectual disability have MetS, routine screening and multidisciplinary management of metabolic abnormalities in people with intellectual disability is needed. Attention should be given to older people and those on antidepressants.

Physical multimorbidity and sedentary behavior in older adults: Findings from the Irish longitudinal study on ageing (TILDA).

BACKGROUND: Physical multimorbidity, defined as the presence of two or more chronic physical conditions, is widespread and reduces life expectancy and quality of life in older adults. Sedentary behavior (SB) is increasingly identified as a risk factor for a range of chronic physical conditions, independent of physical activity. OBJECTIVES: To investigate associations between physical multimorbidity and SB in older adults. STUDY DESIGN: We used cross-sectional data from a population-based sample of 6903 adults aged ≥50 years who participated in the Irish Longitudinal Study on Ageing (TILDA) in 2009-2011. We conducted multivariable linear and logistic regression analyses to assess associations between multimorbidity and SB. MAIN OUTCOME MEASURES: Self-reported minutes/day of SB and high SB (≥ 8 h/day). RESULTS: We found that most of the 14 individual chronic physical conditions included here were associated with greater SB. Those with stroke (OR = 2.63, 95 % CI = 1.69, 4.10) and cirrhosis (OR = 2.53, 95 %CI = 1.19, 5.41) were the most likely to be classified with high SB. Time spent in SB and the prevalence of high SB increased linearly with number of chronic conditions. Multivariable regression models adjusting for sociodemographic and psychological factors, disability, social network, and physical activity showed that, compared with people with none, those with ≥4 chronic physical conditions had 1.45 times greater odds (OR = 1.45, 95 % CI = 1.09, 1.93) of high SB and higher mean minutes/day of SB (ß = 21.37, 95 % CI = 5.53, 37.20). CONCLUSIONS: Our results suggest that physical multimorbidity is associated with SB and highlight the need for prospective research to examine the directionality and mechanisms of these associations.

Sedentary behaviours, cognitive function, and possible mechanisms in older adults: a systematic review.

BACKGROUND: Physical activity can improve cognitive function of older adults, but the influence of sedentary behaviour on cognition is less clear. This systematic review investigated associations between sedentary behaviour and cognitive function in older adults without dementia, and possible mechanisms involved. METHODS: Major databases were searched for studies in English between 01/01/1999 and 31/10/2019. The systematic review followed COSMOS-E guideline and a pre-registered protocol (CRD42019122229). Risk of bias was assessed using NICE Quality appraisal checklist. Findings were narratively synthesized and presented. FINDINGS: Eighteen studies comprised of 13 cross-sectional and five longitudinal analyses (n = 40,228). Evidence suggested varied associations between varied sedentary behaviours and cognitive function in older adults. 50% of study analyses did not control for physical activity. 3/18 studies demonstrated associations between higher sedentary levels and lower levels of brain biomarkers, while 1/18 showed auto-regulatory effect in the left hippocampus. Conducting a meta-analysis was not justifiable due to considerable methodological, participant, outcome and exposure heterogeneity. CONCLUSION: There is a lack of clarity about the overall and independent association between sedentary behaviour and cognition in older age. Underlying mechanisms are similar to physical activity and probably multi-modal. More studies with robust designs and methodology are needed to confirm effect of sedentary behaviour on cognition.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

The association between cardiorespiratory fitness and the incidence of common mental health disorders: A systematic review and meta-analysis.

BACKGROUND: Physical activity is associated with a lower incidence of common mental health disorder, but less is known about the impact of cardiorespiratory fitness (CRF). METHODS: In this review, we systematically evaluated the relationship between CRF and the incidence of common mental health disorders in prospective cohort studies. We systematically searched six major electronic databases from inception to 23rd of May 2019. We assessed study quality using the Newcastle-Ottawa scale. RESULTS: We were able to pool the hazard ratios (HRs) and 95% confidence intervals (CIs) of four studies including at least 27,733,154 person-years of data. We found that low CRF (HR = 1.47, [95% CI 1.23 - 1.76] p < 0.001 I2 = 85.1) and medium CRF (HR = 1.23, [95% CI 1.09 - 1.38] p < 0.001 I2 = 87.20) CRF are associated with a 47% and 23% greater risk of a common mental health disorders respectively, compared with high CRF. We found evidence to suggest a dose-response relationship between CRF and the risk of common mental health disorders. LIMITATIONS: We were only able to identify a small number of eligible studies from our search and heterogeneity was substantial in the subsequent meta-analysis. CONCLUSIONS: Our findings indicate that there is a longitudinal association between CRF levels and the risk of a common mental health disorder. CRF levels could be useful for identifying and preventing common mental health disorders at a population-level.

Increased mortality from somatic multimorbidity in patients with schizophrenia: a Danish nationwide cohort study.

OBJECTIVE: To investigate the association of single- and multimorbidity with mortality rates in patients with schizophrenia compared to the general population. METHOD: A nationwide cohort study including residents in Denmark between 1995 and 2015. The cohort was dichotomously divided by a diagnosis of schizophrenia. Somatic diseases included infections, cancer, endocrine, neurologic, cardiovascular, respiratory, digestive, skin, musculoskeletal, and urogenital diseases. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated. RESULTS: The cohort included 30 210 patients with schizophrenia [mean age (SD) = 32.6 (11.4), males = 57.2%], and 5 402 611 from the general population [mean age (SD) = 33.0 (14.5), males = 50.4%]. All number of somatic diseases were associated with an increased mortality in schizophrenia [HR = 16.3 (95% CI = 15.4-17.3) for 1 disease to 21.0 (95% CI = 19.1-23.0) for ≥5 diseases], using the general population with no somatic disease as reference. Across all somatic diseases, patients with schizophrenia showed a HR > 2, compared to the general population, and respiratory (PAF = 9.3%), digestive (PAF = 8.2%), and cardiovascular (PAF = 7.9%) diseases showed largest contributions to death. CONCLUSIONS: Patients with schizophrenia showed higher mortality on all levels of multimorbidity, and a doubled mortality rate across all somatic diseases, compared to the general population. The findings suggest that the clusters and trajectories of symptoms associated with schizophrenia is the main driver of the excess mortality.

restfulSE: A semantically rich interface for cloud-scale genomics with Bioconductor.

Bioconductor's SummarizedExperiment class unites numerical assay quantifications with sample- and experiment-level metadata.  SummarizedExperiment is the standard Bioconductor class for assays that produce matrix-like data, used by over 200 packages.  We describe the restfulSE package, a deployment of  this data model that supports remote storage.  We illustrate use of SummarizedExperiment with remote HDF5 and Google BigQuery back ends, with two applications in cancer genomics.  Our intent is to allow the use of familiar and semantically meaningful programmatic idioms to query genomic data, while abstracting the remote interface from end users and developers.

Behavioral addictions in bipolar disorders: A systematic review.

Clinical and epidemiological research suggests that behavioral addictions (BA) are associated with a wide range of psychiatric disorders. However, the relationship between BA and bipolar disorders (BD) has not been thoroughly explored. The aim of this systematic review was to critically summarize and evaluate the current available evidence regarding a possible association between BA and BD. A systematic review of major electronic databases according to PRISMA guidelines was conducted from inception to 31st December 2017. We sought quantitative studies data concerning prevalence of comorbidity, features and treatment related to BA-BD comorbidity. Data were narratively synthesized. Of the 1250 studies returned from the search, a total of 28 articles were included in this review. BA may be overrepresented in BD samples, and the other way around. Pathological gambling and kleptomania were the most prevalent conditions followed by compulsive buying, compulsive sexual behavior and internet addiction. BA was also associated with other mood disorders, anxiety disorders and substance use disorder. BD-BA comorbidity was related with more severe course of illness. Studies on treatment strategies for BD-BA comorbidity are rather limited; only one randomized controlled trial that fulfilled inclusion criteria was identified. Methodological heterogeneity in terms of design and results among studies was found. BD-BA commonly co-occurs although there is a need for rigorous studies. Routine screening and adequate assessment may be helpful in BD patients to identify individuals at risk for BA and to effectively manage the complex consequences associated with BA-BD comorbidity.

Psychotic experiences and subjective cognitive complaints among 224 842 people in 48 low- and middle-income countries.

AIMS: Cognitive deficits are an important factor in the pathogenesis of psychosis. Subjective cognitive complaints (SCCs) are often considered to be a precursor of objective cognitive deficits, but there are no studies specifically on SCC and psychotic experiences (PE). Thus, we assessed the association between SCC and PE using data from 48 low- and middle-income countries. METHODS: Community-based cross-sectional data of the World Health Survey were analysed. Two questions on subjective memory and learning complaints in the past 30 days were used to create a SCC scale ranging from 0 to 10 with higher scores representing more severe SCC. The Composite International Diagnostic Interview was used to identify past 12-month PE. Multivariable logistic regression and mediation analyses were performed. RESULTS: The final sample consisted of 224 842 adults aged ⩾18 years [mean (SD) age 38.3 (16.0) years; 49.3% males]. After adjustment for sociodemographic factors, a one-unit increase in the SCC scale was associated with a 1.17 (95% CI 1.16-1.18) times higher odds for PE in the overall sample, with this association being more pronounced in younger individuals: age 18-44 years OR = 1.19 (95% CI 1.17-1.20); 45-64 years OR = 1.15 (95% CI 1.12-1.17); ⩾65 years OR = 1.14 (95% CI 1.09-1.19). Collectively, other mental health conditions (perceived stress, depression, anxiety, sleep problems) explained 43.4% of this association, and chronic physical conditions partially explained the association but to a lesser extent (11.8%). CONCLUSIONS: SCC were associated with PE. Future longitudinal studies are needed to understand temporal associations and causal inferences, while the utility of SCC as a risk marker for psychosis especially for young adults should be scrutinised.