Treatment-Emergent Hypomania Possibly Associated with Over-the-Counter Supplements

The use of complementary and alternative medicine (CAM) is gaining popularity in the Western world. Among the general public, CAM is often perceived to be associated with less stigma, fewer adverse effects, and may be more affordable. A number of patients utilize CAM for the treatment of depression; however, as there is limited scientific evidence, the safety profile of these supplements are largely unknown. In this case, a 42-year-old man developed hypomania approximately 1 week after S-adenosylmethionine (SAMe) and 5-hydroxytryptophan (5-HTP) therapy was initiated for depression. The combination of SAMe and 5-HTP can potentially induce hypomanic episodes

A proposed expert system for nursing practice

The knowledge on which nursing practice is based comes largely from traditional sources, expert nurses passing on the wisdom of their experience to novices. Nursing research, although increasing, is usually parallel to nursing practice, and its findings, at best, are implemented only after long delays. Consequently, the most effective nursing responses to a particular client problem may be undiscovered or unknown. Nursing information systems reflect the nature and usage of nursing knowledge. They offer standard care plans, but the knowledge and decision structures for individualizing care remain exclusively in the mind of the nurse. Nurses may have great freedom to enter information into the information system, but the information is rarely retrievable in a form suitable for evaluation or research. Nursing practice, and the knowledge on which it is based, could be enhanced through the use of a novel expert system. This paper describes how such a system could be developed, with examples from the authors' prototype programs. Taxonomies of data, diagnoses, objectives, and interventions would make it possible to compare patients and to determine the relative effectiveness of nursing interventions. A built-in evaluation component would provide feedback and correction. Everyday nursing practice would become a field for research, and the knowledge gained from research would immediately be fed back into practice. In its development and in its implementation, this kind of system would help to build nursing science.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45001/1/10916_2004_Article_BF00992522.pd

Prioritizing Health-Sector Interventions for Noncommunicable Diseases and Injuries in Low- and Lower-Middle Income Countries: National NCDI Poverty Commissions

Health sector priorities and interventions to prevent and manage noncommunicable diseases and injuries (NCDIs) in low- and lower-middle-income countries (LLMICs) have primarily adopted elements of the World Health Organization Global Action Plan for NCDs 2013–2020. However, there have been limited efforts in LLMICs to prioritize among conditions and health-sector interventions for NCDIs based on local epidemiology and contextually relevant risk factors or that incorporate the equitable distribution of health outcomes. The Lancet Commission on Reframing Noncommunicable Diseases and Injuries for the Poorest Billion supported national NCDI Poverty Commissions to define local NCDI epidemiology, determine an expanded set of priority NCDI conditions, and recommend cost-effective, equitable health-sector interventions. Fifteen national commissions and 1 state-level commission were established from 2016–2019. Six commissions completed the prioritization exercise and selected an average of 25 NCDI conditions; 15 conditions were selected by all commissions, including asthma, breast cancer, cervical cancer, diabetes mellitus type 1 and 2, epilepsy, hypertensive heart disease, intracerebral hemorrhage, ischemic heart disease, ischemic stroke, major depressive disorder, motor vehicle road injuries, rheumatic heart disease, sickle cell disorders, and subarachnoid hemorrhage. The commissions prioritized an average of 35 health-sector interventions based on cost-effectiveness, financial risk protection, and equity-enhancing rankings. The prioritized interventions were estimated to cost an additional US$4.70–US$13.70 per capita or approximately 9.7%–35.6% of current total health expenditure (0.6%–4.0% of current gross domestic product). Semistructured surveys and qualitative interviews of commission representatives demonstrated positive outcomes in several thematic areas, including understanding NCDIs of poverty, informing national planning and implementation of NCDI health-sector interventions, and improving governance and coordination for NCDIs. Overall, national NCDI Poverty Commissions provided a platform for evidence-based, locally driven determination of priorities within NCDIs.publishedVersio

Revisiting the influence of top-down and bottom-up pressures on Wa hia hé:ta (yellow perch Perca flavescens Mitchill, 1814) population dynamics in Kaniatarowanenneh (the Upper St. Lawrence River): Implications for collaborative research

Kaniatarowanenneh (St. Lawrence River) is the outflow of one of the world’s largest freshwater ecosystems and its ecological health has implications for resource management. The population dynamics of an ecologically and economically important fish, the Wa hia hé:ta, Mohawk for yellow perch (Perca flavescens Mitchill, 1814), are considered by including data that extends to the past century to redress temporal gaps in comparative literature. We found both a significant top-down effect from piscivorous fish as well as a significant bottom-up effect related to total phosphorus on yellow perch relative abundance in the Lake Ontario-Upper St. Lawrence system. Regarding the bottom-up effect, the current state of yellow perch reflects the population size prior to cultural eutrophication (pre-1940s/50s) likely responding to the re-oligotrophication of the system. These findings emphasize the importance of considering historical records in fish population dynamics research to incorporate shifting population baselines into fisheries management. The study also demonstrates the need for collaborative approaches that bring critical new insights and multivocality. </jats:p

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders