Conversion of pyridoxal to pyridoxamine with NH and H on nickel generates a protometabolic nitrogen shuttle under serpentinizing conditions.

Serpentinizing hydrothermal vents are likely sites for the origin of metabolism because they produce H as a source of electrons for CO reduction while depositing zero-valent iron, cobalt, and nickel as catalysts for organic reactions. Recent work has shown that solid-state nickel can catalyze the H-dependent reduction of CO to various organic acids and their reductive amination with H and NH to biological amino acids under the conditions of H-producing hydrothermal vents and that amino acid synthesis from NH, H, and 2-oxoacids is facile in the presence of Ni. Such reactions suggest a metallic origin of metabolism during early biochemical evolution because single metals replace the function of over 130 enzymatic reactions at the core of metabolism in microbes that use the acetyl-CoA pathway of CO fixation.

Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

Objectives: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.

Methods: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States.

Real-world community hospital hyperglycemia management in noncritically ill, type 2 diabetic patients: a comparison between basal-bolus insulin and correctional insulin.

Purpose: This study evaluated the safety and efficacy of two insulin regimens for inpatient hyperglycemia management: combination short-plus long-acting insulin (basal-bolus insulin regimen, BBIR) vs. short-acting insulin only (correctional insulin only regimen, CIOR).

Methods: Chart reviews identified noncritically ill patients with pre-existing type 2 diabetes mellitus receiving insulin injections.

Differential effects of cannabis constituents on schizophrenia-related psychosis: a rationale for incorporating cannabidiol into a schizophrenia therapeutic regimen.

Schizophrenia is a serious mental health disorder that confers one of the highest mortality rates of all psychiatric illnesses. Although the disorder's psychotic symptoms are treatable with conventional antipsychotics, they remain incurable. Moreover, medication adherence is poor, and individuals with schizophrenia choose to self-medicate with illicit substances, including cannabis.

Assessment of education in a community hospital on healthcare providers' knowledge of and attitudes toward medical marijuana.

Introduction: Although medical marijuana usage continues to become more socially acceptable and is increasingly regarded as a legitimate treatment alternative for certain medical conditions such as cancer and epilepsy, stigma remains.

Methods: This study examined whether offering an educational session addressing several key aspects of medical marijuana (e.g.

Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.

Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2, a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome.

Hypomorphic variants of SEL1L-HRD1 ER-associated degradation are associated with neurodevelopmental disorders.

Recent studies using cell type-specific knockout mouse models have improved our understanding of the pathophysiological relevance of suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) endoplasmic reticulum-associated (ER-associated) degradation (ERAD); however, its importance in humans remains unclear, as no disease variant has been identified. Here, we report the identification of 3 biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia. These SEL1L (p.

Exome-wide association study of treatment-resistant depression suggests novel treatment targets.

Treatment-resistant depression (TRD) is a severe form of major depressive disorder (MDD) with substantial public health impact and poor treatment outcome. Treatment outcome in MDD is significantly heritable, but genome-wide association studies have failed to identify replicable common marker alleles, suggesting a potential role for uncommon variants. Here we investigated the hypothesis that uncommon, putatively functional genetic variants are associated with TRD.

Evidence for proton-pump inhibitor (PPI)-associated dysbiosis in metabolically unhealthy obesity.

Obesity adversely impacts millions of American adults by predisposing them to significant health risks and further complications. Obesity is differentiated into two groups: metabolically healthy and metabolically unhealthy. In contrast to metabolically healthy counterparts, obese individuals who are metabolically unhealthy display hallmark symptoms of metabolic syndrome (, hypertension, dyslipidemia, hyperglycemia, abdominal obesity).

Investigation of the stress reduction and temperature increase due to ultrasonic vibrations with different amplitudes during compression tests of steels with varying specimen sizes.

High-frequency vibrations in the ultrasonic range influence the plasticity of metals during metal forming: there is stress and force reduction during ultrasonic treatment compared to metal forming without ultrasound. Different reasons for this behavior are discussed: a combination of stress superposition, energy absorption in dislocations, temperature increase, and frictional changes. This investigation shows the influence of partially superimposed ultrasonic vibrations with amplitudes in the range of ∼ 1.

The pharmacist's role in reducing infusion-related phlebitis.

Purpose: Pharmacists oversee parenteral drug preparation and administration in hospitals, clinics, infusion centers, and home infusion settings. Infusion-related phlebitis (IRP), the most common complication of intravenous infusion therapy, significantly impacts therapeutic outcomes, patient satisfaction, cost of care, and provider workload. Here we review the major etiologies of IRP and describe potential pharmacological and nonpharmacological interventions for preventing and managing the condition as well as for improving vascular access health in multiple-drug administration settings.

Effectiveness of gamified team competition as mHealth intervention for medical interns: a cluster micro-randomized trial.

Gamification, the application of gaming elements to increase enjoyment and engagement, has the potential to improve the effectiveness of digital health interventions, while the effectiveness of competition gamification components remains poorly understood on residency. To address this gap, we evaluate the effect of smartphone-based gamified team competition intervention on daily step count and sleep duration via a micro-randomized trial on medical interns. Our aim is to assess potential improvements in the factors (namely step count and sleep) that may help interns cope with stress and improve well-being.

Polygenic Risk and Social Support in Predicting Depression Under Stress.

Objective: Despite substantial progress in identifying genomic variation associated with major depression, the mechanisms by which genomic and environmental factors jointly influence depression risk remain unclear. Genomically conferred sensitivity to the social environment may be one mechanism linking genomic variation and depressive symptoms. The authors assessed whether social support affects the likelihood of depression development differently across the spectrum of genomic risk in two samples that experienced substantial life stress: 1,011 first-year training physicians (interns) in the Intern Health Study (IHS) and 435 recently widowed Health and Retirement Study (HRS) participants.

Three-Fluorophore FRET Enables the Analysis of Ternary Protein Association in Living Plant Cells.

Protein-protein interaction studies provide valuable insights into cellular signaling. Brassinosteroid (BR) signaling is initiated by the hormone-binding receptor Brassinosteroid Insensitive 1 (BRI1) and its co-receptor BRI1 Associated Kinase 1 (BAK1). BRI1 and BAK1 were shown to interact independently with the Receptor-Like Protein 44 (RLP44), which is implicated in BRI1/BAK1-dependent cell wall integrity perception.

FIBCD1 is an endocytic GAG receptor associated with a novel neurodevelopmental disorder.

Whole-exome sequencing of two patients with idiopathic complex neurodevelopmental disorder (NDD) identified biallelic variants of unknown significance within FIBCD1, encoding an endocytic acetyl group-binding transmembrane receptor with no known function in the central nervous system. We found that FIBCD1 preferentially binds and endocytoses glycosaminoglycan (GAG) chondroitin sulphate-4S (CS-4S) and regulates GAG content of the brain extracellular matrix (ECM). In silico molecular simulation studies and GAG binding analyses of patient variants determined that such variants are loss-of-function by disrupting FIBCD1-CS-4S association.

Prevalence and risk factors for depression among training physicians in China and the United States.

During their first year of medical residency (internship), 35% of training physicians in the United States suffer at least one depression episode. We assessed whether there is a similar increase of depression among first year residents in China, and identified predictors of depression in the two systems. 1006 residents across three cohorts (2016-2017, 2017-2018 and 2018-2019) at Shanghai Jiao Tong University and Peking Union Medical College were assessed in parallel with three cohorts of 7028 residents at 100 + US institutions.

Genetic interactions with stressful environments in depression and addiction.

Stress is the most important proximal precipitant of depression, yet most large genome-wide association studies (GWAS) do not include stress as a variable. Here, we review how gene × environment (G × E) interaction might impede the discovery of genetic factors, discuss two examples of G × E interaction in depression and addiction, studies incorporating high-stress environments, as well as upcoming waves of genome-wide environment interaction studies (GWEIS). We discuss recent studies which have shown that genetic distributions can be affected by social factors such as migrations and socioeconomic background.

Functional Study of Gene Variants Associated with Hypomyelination Leukodystrophy.

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants.

Neuropeptide Y Variation Is Associated With Altered Static and Dynamic Functional Connectivity of the Salience Network.

Neuropeptide Y (NPY) is a neurotransmitter that has been implicated in the development of anxiety and mood disorders. Low levels of NPY have been associated with risk for these disorders, and high levels with resilience. Anxiety and depression are associated with altered intrinsic functional connectivity of brain networks, but the effect of NPY on functional connectivity is not known.