Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans.

Background: Apolipoprotein L1 gene () variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of variants with CKD in West Africans, a major group in the Black population.

Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease.

A deployable curriculum with 3D printed skills trainers for altered airway management.

Background: Altered Airway Anatomy (AAA), including tracheostomies and laryngectomies, may represent an area of unease for non-Otolaryngology trainees, due to a lack of exposure, structured education, or dedicated training in altered airway management. Inability to effectively stabilize an altered airway is associated with significant risk of patient morbidity and mortality. This study aims to assess the efficacy of a concise curriculum using three-dimensional (3D) printed airway models for skill training in improving Anesthesiology trainees' competency in AAA management.

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.

Suppression of Vascular Macrophage Activation by Nitro-Oleic Acid and its Implication for Abdominal Aortic Aneurysm Therapy.

Purpose: Abdominal aortic aneurysm (AAA) is one of the leading causes of death in the developed world and is currently undertreated due to the complicated nature of the disease. Herein, we aimed to address the therapeutic potential of a novel class of pleiotropic mediators, specifically a new drug candidate, nitro-oleic acid (NO-OA), on AAA, in a well-characterized murine AAA model.

Methods: We generated AAA using a mouse model combining AAV.

A Nationwide Study Assessing Preventable Hospitalization Rate on Mortality After Major Cardiovascular Surgery.

Despite the use of various factors to measure hospital quality, most measures have not resulted in long-term improvements in patient outcomes. This study's purpose is to determine the effect of a previously unassessed measure of quality of care-a hospital's preventable hospitalization rate-on 30-day mortality at both the hospital and individual levels after three major cardiovascular surgery procedures. This is a population-based study using Taiwan's National Health Insurance database.

Drug Targeting of Plasminogen Activator Inhibitor-1 Inhibits Metabolic Dysfunction and Atherosclerosis in a Murine Model of Metabolic Syndrome.

Objective: Enhanced expression of PAI-1 (plasminogen activator inhibitor-1) has been implicated in atherosclerosis formation in humans with obesity and metabolic syndrome. However, little is known about the effects of pharmacological targeting of PAI-1 on atherogenesis. This study examined the effects of pharmacological PAI-1 inhibition on atherosclerosis formation in a murine model of obesity and metabolic syndrome.

Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis.

Deciphering novel pathways regulating liver lipid content has profound implications for understanding the pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Recent evidence suggests that the nuclear envelope is a site of regulation of lipid metabolism but there is limited appreciation of the responsible mechanisms and molecular components within this organelle. We showed that conditional hepatocyte deletion of the inner nuclear membrane protein lamina-associated polypeptide 1 (LAP1) caused defective VLDL secretion and steatosis, including intranuclear lipid accumulation.

Early Impact of Medicare Accountable Care Organizations on Inpatient Surgical Spending.

Objective: To evaluate whether hospital participation in accountable care organizations (ACOs) is associated with reduced Medicare spending for inpatient surgery.

Background: ACOs have proliferated rapidly and now cover more than 32 million Americans. Medicare Shared Savings Program (MSSP) ACOs have shown modest success in reducing medical spending.

TorsinA dysfunction causes persistent neuronal nuclear pore defects.

A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons.

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores.

Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C.

Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

Background: This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism.

Methods: Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues.

Mechanism of Vps4 hexamer function revealed by cryo-EM.

Vps4 is a member of AAA ATPase (adenosine triphosphatase associated with diverse cellular activities) that operates as an oligomer to disassemble ESCRT-III (endosomal sorting complex required for transport III) filaments, thereby catalyzing the final step in multiple ESCRT-dependent membrane remodeling events. We used electron cryo-microscopy to visualize oligomers of a hydrolysis-deficient Vps4 (vacuolar protein sorting-associated protein 4) mutant in the presence of adenosine 5'-triphosphate (ATP). We show that Vps4 subunits assemble into an asymmetric hexameric ring following an approximate helical path that sequentially stacks substrate-binding loops along the central pore.

Hospital Teaching Status and Medicare Expenditures for Complex Surgery.

Objective: To evaluate the relationship between hospital teaching intensity, Medicare payments, and perioperative outcomes.

Background: Several emerging payment policies penalize hospitals for low-value healthcare. Teaching hospitals may be at a disadvantage given the perception that they deliver care less efficiently.

Interaction of expanding abdominal aortic aneurysm with surrounding tissue: Retrospective CT image studies.

Objectives: Abdominal aortic aneurysms (AAA) that rupture have a high mortality rate. Rupture occurs when local mechanical stress exceeds the local mechanical strength of an AAA, so stress profiles such as those from finite element analysis (FEA) are useful. The role and effect of surrounding tissues, like the vertebral column, which have not been extensively studied, are examined in this paper.

Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9.

We hypothesized that matrix metalloproteinase secretion in response to cigarette smoke is modulated by cross-talk between resident cells within the aorta, namely, aortic smooth muscles, endothelial cells, and infiltrating macrophages, and this may be crucial for in vivo formation/progression of abdominal aortic aneurysm (AAA). Cigarette smoke extract (CSE) was applied to rat aortic smooth muscle (RASMC), endothelial (RAEC) or RAW cells, and conditioned media (CSE-CM) collected. Fresh cells were treated with CSE-CM for 24 h and then maintained in serum-free medium (SFM) for 72 h to analyze MMP2 and MMP9 in media by zymography and the ratio (pS/pJ) of phospho-Stat3 (pStat3) and phospho-Jak2 (pJak2) inside the cells by Western blot.

Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endoplasmic reticulum.

TorsinA (also known as torsin-1A) is a membrane-embedded AAA+ ATPase that has an important role in the nuclear envelope lumen. However, most torsinA is localized in the peripheral endoplasmic reticulum (ER) lumen where it has a slow mobility that is incompatible with free equilibration between ER subdomains. We now find that nuclear-envelope-localized torsinA is present on the inner nuclear membrane (INM) and ask how torsinA reaches this subdomain.

A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import.

Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE.

Cigarette smoke-induced MMP2 and MMP9 secretion from aortic vascular smooth cells is mediated via the Jak/Stat pathway.

It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 (P = .005) and a modest increase in pro-MMP2 (P = .

Vps4 stimulatory element of the cofactor Vta1 contacts the ATPase Vps4 α7 and α9 to stimulate ATP hydrolysis.

The endosomal sorting complexes required for transport (ESCRTs) function in a variety of membrane remodeling processes including multivesicular body sorting, abscission during cytokinesis, budding of enveloped viruses, and repair of the plasma membrane. Vps4 ATPase activity modulates ESCRT function and is itself modulated by its cofactor Vta1 and its substrate ESCRT-III. The carboxyl-terminal Vta1/SBP-1/Lip5 (VSL) domain of Vta1 binds to the Vps4 β-domain to promote Vps4 oligomerization-dependent ATP hydrolysis.

Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4 stimulatory element.

The endosomal sorting complexes required for transport (ESCRTs) impact multiple cellular processes including multivesicular body sorting, abscission, and viral budding. The AAA-ATPase Vps4 is required for ESCRT function, and its full activity is dependent upon the co-factor Vta1. The Vta1 carboxyl-terminal Vta1 SBP1 Lip5 (VSL) domain stimulates Vps4 function by facilitating oligomerization of Vps4 into its active state.

A cell permeant peptide containing the cytoplasmic tail sequence of Fc receptor type IIA reduces calcium signaling and phagolysosome formation in neutrophils.

Receptors for the Fc domain of IgG mediate target recognition, signal transduction, and effector functions including antibody-dependent cytolysis, phagocytosis, and phagolysosome formation. To better understand FcR-mediated functions and to identify potential therapeutic strategies, we employed cell-penetrating ("Trojan") peptides to deliver "wild-type" (LTL) or modified (AAA) FcgammaRIIA tail sequences to the neutrophil's cytoplasm. The Trojan-LTL peptide appeared to label the endoplasmic reticulum whereas the Trojan-AAA peptide distributed throughout the cytoplasm.