Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Preferential Synaptic Type of GABA-A Receptor Ligands Enhancing Neuronal Survival and Facilitating Functional Recovery After Ischemic Stroke.

Selective enhancement of synaptic GABA signaling mediated by GABA-A receptors has been previously reported to promote functional recovery after ischemic stroke, while tonic GABA signaling has been detrimental. To identify agents that enhance synaptic signaling, we synthesized GABA-A ligands based on three chemotypes with affinity values p= 6.44-8.

Vaccination status of patients with primary immunodeficiencies in Germany-a multicentric epidemiologic analysis.

Background: Vaccinations represent an easily accessible, safe, and important method for preventing infections. Patients with primary immunodeficiencies (PID) are more susceptible to infections and should receive an extended spectrum of immunizations in many countries.

Methods: Between January 2019 and May 2020, vaccination certificates of 70 patients with PID from the regions of Würzburg and Hanover in Germany were evaluated.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD.

Cardiac Arrhythmias in Oncological Patients-Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines.

Purpose Of Review: To provide an update on epidemiology, risk factors, and management of cardiac arrhythmias in oncological patients within the context of the new European Society of Cardiology 2022 guidelines on cardio-oncology.

Recent Findings: One of the side effects of different chemotherapeutics is their pro-arrhythmic activity. Both atrial and ventricular arrhythmias may be induced by cancer itself or by anticancer treatment.

Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis.

Background: Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis.

Virus variant-specific clinical performance of SARS coronavirus two rapid antigen tests in point-of-care use, from November 2020 to January 2022.

Objectives: Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC.

Promising anticonvulsant and/or analgesic compounds among 5-chloro-2- or 5-chloro-4-methyl derivatives of xanthone coupled to aminoalkanol moieties-Design, synthesis and pharmacological evaluation.

A series of 10 aminoalkanol derivatives of 5-chloro-2- or 5-chloro-4-methylxanthone was synthetized and evaluated for anticonvulsant properties (MES test, mice, intraperitoneal) and compared with neurotoxicity rotarod test (NT, mice, i.p.).

Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics.

In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound.

Evaluation of the predictivity of Acute Oral Toxicity (AOT) structure-activity relationship models.

Several public efforts are aimed at discovering patterns or classifiers in the high-dimensional bioactivity space that predict tissue, organ or whole animal toxicological endpoints. The current study sought to assess and compare the predictions of the Globally Harmonized System (GHS) categories and Dangerous Goods (DG) classifications based on Lethal Dose (LD50) from several available tools (ACD/Labs, Leadscope, T.E.

Qualitative coronary artery calcification scores and risk of all cause, COPD and pneumonia hospital admission in a large CT lung cancer screening cohort.

Background: Patients at high-risk for lung cancer and qualified for CT lung cancer screening (CTLS) are at risk for numerous cardio-pulmonary comorbidities. We sought to examine if qualitatively assessed coronary artery calcifications (CAC) on CTLS exams could identify patients at increased risk for non-cardiovascular events such as all cause, COPD and pneumonia related hospitalization and to verify previously reported associations between CAC and mortality and cardiovascular events.

Study Design And Methods: Patients (n = 4673) from Lahey Hospital and Medical Center who underwent CTLS from January 12, 2012 through September 30, 2017 were included with clinical follow-up through September 30, 2019.

Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF.

Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC-MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified.

Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR.

Background: Antigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data from large field studies is sparse.

Methods: In a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®, conducted on different samples) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting.

Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age.

Background: Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified.

Aims: To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval.

Use of Complementary and Alternative Medicine in Patients with Primary Immunodeficiency: a Multicentric Analysis of 101 Patients.

The term complementary and alternative medicine (CAM) describes a broad spectrum of health care practices that are not an integral part of the conventional health care system. Many patients worldwide use CAM on their own initiative, often in combination with their conventional medical therapy. CAM use is attractive especially to patients with primary immunodeficiency, since they suffer from frequent infections and autoimmunity.

Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study.

Background: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission.

Wernicke-Kleist-Leonhard phenotypes of endogenous psychoses: a review of their validity .

While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-Leonhard (WKL) pathway has optimized the descriptions of 35 major phenotypes using common medical heuristics on lifelong diachronic observations.

Identification and characterization of citalopram new metabolites with the use of UHPLC-Q-TOF technique: In silico toxicity assessment of the identified transformation products.

In this study the metabolite profiling of citalopram with the use of human liver microsomes as well as the complementary photocatalytic method were established. This strategy allowed the detection of five metabolites of citalopram including 3-hydroxycitalopram and 3-oxocitalopram which were found as a new and not previously described metabolites of this drug The photocatalytic simulation of metabolism was carried out using tungsten (VI) oxide nanopowders with the different particle sizes, which allowed to examine the effect of this photocatalyst parameter on the mapping of metabolic processes. The accurate characterization of all observed structures was possible due to the use of ultra-high-pressure liquid chromatography and high-resolution mass spectrometry combined system as a highly useful technique in drug metabolism studies.

Hierarchical Composite Meshes of Electrospun PS Microfibers with PA6 Nanofibers for Regenerative Medicine.

One of the most frequently applied polymers in regenerative medicine is polystyrene (PS), which is commonly used as a flat surface and requires surface modifications for cell culture study. Here, hierarchical composite meshes were fabricated via electrospinning PS with nylon 6 (PA6) to obtain enhanced cell proliferation, development, and integration with nondegradable polymer fibers. The biomimetic approach of designed meshes was verified with a scanning electron microscope (SEM) and MTS assay up to 7 days of cell culture.

Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS.

Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO and WS assisted photochemical reactions.