NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation.

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress.

Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

Background: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses.

Methods And Findings: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs.

Evaluation of pharmacists' awareness of illegal online pharmacies and perceived impact on safe access to medicines.

Background: An estimated 95% of all online pharmacies operate unlawfully. Illegal online pharmacies distribute substandard and falsified medical products that may result in patient harm and suboptimal treatment, leading to an overall mistrust of medications, healthcare providers, and health systems. As medication experts, pharmacists are trusted to guide patients in selection of safe and effective medication therapy.

Rising to the Occasion of This COVID-19-Impacted Nation: Development, Implementation, and Feasibility of the Brief Assessment-Informed Skills Intervention for COVID-19 (BASIC).

The COVID-19 pandemic has had a profound impact on the global economy, physical health, and mental health. This pandemic, like previous viral outbreaks, has resulted in spikes in anxiety, depression, and stress. Even though millions of individuals face the physical health consequences of infection by COVID-19, even more individuals are confronted with the mental health consequences of this pandemic.

Sleeve Gastrectomy Is Associated with a Greater Reduction in Plasma Liver Enzymes Than Bypass Surgeries-A Registry-Based Two-Year Follow-Up Analysis.

Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) on the levels of ALT by analysis of two-year follow-up data from 4980 patients in the Israeli Bariatric Registry that included laboratory tests and demographic information. Pre-operative characteristics of patients, and particularly levels of liver enzymes, were similar across surgery types.

New Brucella variant isolated from Croatian cattle.

Background: A novel Brucella strain closely related to Brucella (B.) melitensis biovar (bv) 3 was found in Croatian cattle during testing within a brucellosis eradication programme.

Case Presentation: Standardised serological, brucellin skin test, bacteriological and molecular diagnostic screening for Brucella infection led to positive detection in one dairy cattle herd.

Association Between Contact Precautions and Transmission of Methicillin-Resistant Staphylococcus aureus in Veterans Affairs Hospitals.

Importance: The effectiveness and importance of contact precautions for endemic pathogens has long been debated, and their use has broad implications for infection control of other pathogens.

Objective: To estimate the association between contact precautions and transmission of methicillin-resistant Staphylococcus aureus (MRSA) across US Department of Veterans Affairs (VA) hospitals.

Design, Setting, And Participants: This retrospective cohort study used mathematical models applied to data from a population-based sample of adults hospitalized in 108 VA acute care hospitals for at least 24 hours from January 1, 2008, to December 31, 2017.

Referral Patterns and Treatment Delays in Medulloblastoma: A Large Academic Proton Center Experience.

Purpose: Patient travel time can cause treatment delays when providers and families decide to seek proton therapy. We examined whether travel distance or referral pattern (domestic versus international) affects time to radiation therapy and subsequent disease outcomes in patients with medulloblastoma at a large academic proton center.

Patients And Methods: Children with medulloblastoma treated at MD Anderson (MDA) with a protocol of proton beam therapy (PBT) between January 4, 2007, and June 25, 2014, were included in the analysis.

Patient-derived xenografts and organoids model therapy response in prostate cancer.

Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor.

The tumor immune contexture of salivary duct carcinoma.

Background: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. Recently, biomarker studies found promising targetable alterations. In this study, we provide a descriptive analysis of tumor and immune biomarkers and survival associations.

Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?

Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function.

Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer.

Purpose: Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.

Patient And Methods: We present a case of whole-genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available.

Endoscopic Phenotype of the J Pouch in Patients With Inflammatory Bowel Disease: A New Classification for Pouch Outcomes.

Background & Aims: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype.

Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer.

Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP.

Ulcerative Colitis Narrative Global Survey Findings: The Impact of Living With Ulcerative Colitis-Patients' and Physicians' View.

Background: The Ulcerative Colitis (UC) Narrative is a global patient and physician survey aimed at identifying the impact of UC and comparing and contrasting perceptions of UC burden and management approaches.

Methods: Surveys of patients with UC (self-reported diagnosis; n = 2100) and physicians (n = 1254) were completed across 10 countries by The Harris Poll between August 2017 and February 2018. Questionnaires covered multiple aspects of UC, including diagnosis, treatment, and impact on patient quality of life, in addition to standard demographic information.

Matching Methods to Problems: Using Data Science and Transmission Modeling to Combat Antimicrobial Resistance.

Antimicrobial resistance is a growing worldwide crisis, declared by the World Health Organization as "one of the principal threats to global public health today." The emergence and spread of antimicrobial resistance is a multifaceted problem that spans all aspects of healthcare, and research efforts to advance the field must likewise employ investigators with a diverse set of expertise and a variety of approaches and study designs who recognize and address the unique challenges of infectious-disease and antimicrobial-resistance research. An understanding of transmission dynamics and externalities, both positive and negative, is critical to any assessment of the impact of an intervention or policy related to infectious disease, infection prevention, or antimicrobial stewardship, in order to create a more comprehensive and accurate estimate of the costs and outcomes associated with an intervention.

Expanding an Economic Evaluation of the Veterans Affairs (VA) Methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative to Include Prevention of Infections From Other Pathogens.

Background: In October 2007, Veterans Affairs (VA) launched a nationwide effort to reduce methicillin-resistant Staphylococcus aureus (MRSA) transmission called the National MRSA Prevention Initiative. Although the initiative focused on MRSA, recent evidence suggests that it also led to a significant decrease in hospital-onset (HO) gram-negative rod (GNR) bacteremia, vancomycin-resistant Enterococci (VRE), and Clostridioides difficile infections. The objective of this analysis was to evaluate the cost-effectiveness and the budget impact of the initiative taking into account MRSA, GNR, VRE, and C.

Loss and revival of androgen receptor signaling in advanced prostate cancer.

Targeting the androgen receptor (AR) signaling axis has been, over decades, the mainstay of prostate cancer therapy. More potent inhibitors of androgen synthesis and antiandrogens have emerged and have been successfully implemented in clinical practice. That said, the stronger inhibition of the AR signaling axis has led in recent years to an increase of prostate cancers that de-differentiate into AR-negative disease.

Guidance for Physicians Who Wish to Influence Policy Development on Determination of Death by Neurologic Criteria.

Physicians have a long-standing obligation to consider social implications of their practice and its potential influences on health policy. One example of a practice's influence on policy is determining death by neurologic criteria. By lobbying policymakers, maintaining their diagnostic skills, participating in national medical societies, and contributing to robust discourse, physicians can positively influence practice and policy about death determination by neurologic criteria.

Preparation of spiro[indole-3,5'-isoxazoles] Grignard conjugate addition/spirocyclization sequence.

A highly efficient one-pot procedure combining conjugate addition of Grignard reagents to (2-nitroalkenyl)indoles and sub-sequent Brønsted acid-assisted spirocyclization allowed for preparation of 4'-spiro[indole-3,5'-isoxazoles] in a diastereomerically selective fashion. Utilization of alkyl Grignard reagents provided an easy access to 4'-alkylsubstituted derivatives hardly available by other means.

[Molecular pathology of urogenital tumors : Recommendations from the 2019 International Society of Urological Pathology (ISUP) Consensus Conference].

Comprehensive understanding of molecular principles in cancer and the diversification of oncological therapy promise individual therapeutic concepts, which have not yet found their way into urogenital cancer therapy. In March 2019 the International Society of Urogenital Pathology (ISUP) therefore held a consensus conference on recommendations for molecular diagnostics of genitourinary tumors, which were published in five separate manuscripts and are summarized in this article.In preparation for the conference, a comprehensive survey of current practices for molecular testing of urogenital tumors was carried out by members of the ISUP.

Vitamin D Status and COVID-19 Clinical Outcomes in Hospitalized Patients.

: Populations severely affected by COVID-19 are also at risk for vitamin D deficiency. Common risk factors include older age, chronic illness, obesity, and non-Caucasian race. Vitamin D deficiency has been associated with risk for respiratory infections and failure, susceptibility and response to therapy for enveloped virus infection, and immune-mediated inflammatory reaction.