A Gut-Restricted Lithocholic Acid Analog as an Inhibitor of Gut Bacterial Bile Salt Hydrolases.

Bile acids play crucial roles in host physiology by acting both as detergents that aid in digestion and as signaling molecules that bind to host receptors. Gut bacterial bile salt hydrolase (BSH) enzymes perform the gateway reaction leading to the conversion of host-produced primary bile acids into bacterially modified secondary bile acids. Small molecule probes that target BSHs will help elucidate the causal roles of these metabolites in host physiology.

Perceived COVID-19-related anti-Asian discrimination predicts post traumatic stress disorder symptoms among Asian and Asian American young adults.

Objective: This study investigates the prevalence of COVID-19-related discrimination and the extent to which COVID-19-related discrimination is associated with mental health symptoms among Asians and Asian American (A/AA) young adults during the first three months of the COVID-19 pandemic.

Methods: We used data from the COVID-19 Adult Resilience Experiences Study (CARES), a cross-sectional online survey conducted in the U.S.

Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19.

Objective: To explore the spectrum of skeletal muscle and nerve pathology of patients who died after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to assess for direct viral invasion of these tissues.

Methods: Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died after SARS-CoV-2 infection and 10 SARS-CoV-2-negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review.

Diminished Learning Over Repeated Exposures (LORE) in preclinical Alzheimer's disease.

Introduction: We determine whether diminished Learning Over Repeated Exposures (LORE) identifies subtle memory decrements in cognitively unimpaired (CU) older adults with Alzheimer's disease (AD) biomarker burden.

Methods: Ninety-four CU participants (mean age = 77.6 ± 5.

Structure, Dynamics and Function of the 26S Proteasome.

The 26S proteasome is the most complex ATP-dependent protease machinery, of ~2.5 MDa mass, ubiquitously found in all eukaryotes. It selectively degrades ubiquitin-conjugated proteins and plays fundamentally indispensable roles in regulating almost all major aspects of cellular activities.

Effect of High-Dose vs Standard-Dose Vitamin D Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D (4000 IU) or standard-dose (400 IU) vitamin D. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks).

PCSK9 loss of function is protective against extra-coronary atherosclerotic cardiovascular disease in a large multi-ethnic cohort.

Background: Therapeutic inhibition of PCSK9 protects against coronary artery disease (CAD) and ischemic stroke (IS). The impact on other diseases remains less well characterized.

Methods: We created a genetic risk score (GRS) for PCSK9 using four single nucleotide polymorphisms (SNPs) at or near the PCSK9 locus known to impact lower LDL-Cholesterol (LDL-C): rs11583680, rs11591147, rs2479409, and rs11206510.

Editor's Choice - Mortality is High Following Elective Open Repair of Complex Abdominal Aortic Aneurysms.

Objective: To evaluate the 30 day mortality of elective open complex abdominal aortic aneurysm (cAAA) repair and identify factors associated with death.

Methods: This was a retrospective cohort study using a Targeted Vascular Module from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP). All patients undergoing elective repair for juxta- and suprarenal abdominal aortic aneurysm (AAA), or type IV thoraco-abdominal aneurysms (TAAA) from 2011 to 2017 were identified.

Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program.

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability.

Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls.

Reduced Nhe1 (Na-H Exchanger-1) Function Protects ApoE-Deficient Mice From Ang II (Angiotensin II)-Induced Abdominal Aortic Aneurysms.

IgE-mediated activation of Nhe1 (Na-H exchanger-1) induces aortic cell extracellular acidification and promotes cell apoptosis. A pH-sensitive probe pHrodo identified acidic regions at positions of macrophage accumulation, IgE expression, and cell apoptosis in human and mouse abdominal aortic aneurysm (AAA) lesions. Ang II (angiotensin II)-induced AAA in Nhe1-insufficient mice and littermates tested Nhe1 activity in experimental AAA, because mice develop ataxia and epileptic-like seizures and die early.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

Background And Purpose: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent.

Materials And Methods: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019.

Thoracic Endovascular Aortic Repair With Left Subclavian Artery Coverage Is Associated With a High 30-Day Stroke Incidence With or Without Concomitant Revascularization.

To evaluate the perioperative stroke incidence following thoracic endovascular aortic repair (TEVAR) with differing left subclavian artery (LSA) coverage and revascularization approaches in a real-world setting of a nationwide clinical registry. The National Surgical Quality Improvement Program registry was interrogated from 2005 to 2017 to identify all nonemergent TEVAR and/or open LSA revascularization procedures. In this time frame, 2346 TEVAR cases met the selection criteria for analysis.

Mortality from abdominal aortic aneurysm: trends in European Union 15+ countries from 1990 to 2017.

Background: This observational study assessed trends in abdominal aortic aneurysm (AAA) death rates in European Union (EU) 15+ countries for the years 1990 to 2017.

Methods: Age-standardized death rates (ASDRs) were extracted from the Global Burden of Disease Study Global Health Data Exchange. Trends were analysed using joinpoint regression analysis.

Contemporary mortality after emergent open repair of complex abdominal aortic aneurysms.

Objective: Mortality after open repair for emergent complex abdominal aortic aneurysm (AAA) is poorly defined. This study evaluated the 30-day mortality of open complex AAA repair performed for rupture or other emergent indication using a national surgical registry. We subsequently identified factors associated with mortality.

COVID-19 and neuromuscular disorders.

The coronavirus 2019 (COVID-19) pandemic has potential to disproportionately and severely affect patients with neuromuscular disorders. In a short period of time, it has already caused reorganization of neuromuscular clinical care delivery and education, which will likely have lasting effects on the field. This article reviews (1) potential neuromuscular complications of COVID-19, (2) assessment and mitigation of COVID-19-related risk for patients with preexisting neuromuscular disease, (3) guidance for management of immunosuppressive and immunomodulatory therapies, (4) practical guidance regarding neuromuscular care delivery, telemedicine, and education, and (5) effect on neuromuscular research.

Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine.

SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development of a selective SRC inhibitor has been challenging, and FDA-approved SRC inhibitors, dasatinib and bosutinib, are multitargeted kinase inhibitors. Here, we describe our efforts to develop a selective SRC covalent inhibitor by targeting cysteine 277 on the P-loop of SRC.

The Impact of Proximal Clamp Location on Peri-Operative Outcomes Following Open Surgical Repair of Juxtarenal Abdominal Aortic Aneurysms.

Objective: Open surgical repair of juxtarenal abdominal aortic aneurysms (AAA) requires an aortic cross clamp location above at least one renal artery. This study investigated the impact of clamp location on peri-operative outcomes using a United States based nationwide clinical registry.

Methods: The National Surgical Quality Improvement Program targetted vascular module was used to identify all elective open juxtarenal AAA repairs (2011-2017).

The case for expanding abdominal aortic aneurysm screening.

Both the U.S. Preventive Services Task Force and the UK National Institute for Health and Care Excellence are re-evaluating their screening paradigms for abdominal aortic aneurysms (AAAs).

Screening for Abdominal Aortic Aneurysm: US Preventive Services Task Force Recommendation Statement.

Importance: An abdominal aortic aneurysm (AAA) is typically defined as aortic enlargement with a diameter of 3.0 cm or larger. The prevalence of AAA has declined over the past 2 decades among screened men 65 years or older in various European countries.

Effect of Aflibercept Plus Modified FOLFOX6 Induction Chemotherapy Before Standard Chemoradiotherapy and Surgery in Patients With High-Risk Rectal Adenocarcinoma: The GEMCAD 1402 Randomized Clinical Trial.

Importance: Preclinical studies suggest that a vascular endothelial growth factor (VEGF) blockade may play a role in the preoperative treatment of rectal adenocarcinoma; however, how to combine anti-VEGF drugs with neoadjuvant chemotherapy (CT) and/or chemoradiotherapy (CRT) remains controversial.

Objective: To study the effect of aflibercept plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) induction CT prior to standard CRT and total mesorectal excision (TME) surgery in patients with high-risk rectal adenocarcinoma.

Design, Setting, And Participants: In the Grupo Español Multidisciplinar En Cancer Digestivo (GEMCAD) 1402 phase 2 randomized clinical trial, 180 patients aged 18 to 75 years, identified by centrally reviewed magnetic resonance imaging to have mrT3c-d/T4/N2 rectal adenocarcinoma, were enrolled from 20 treatment centers in Spain between January 2015 and March 2017.