Impending Backlog of Cleft Palate Patients Due to COVID-19.

Coronavirus disease 2019 (COVID-19) has placed an unprecedented strain on healthcare systems worldwide, but while high-income countries (HICs) have been able to adapt, low- and middle-income countries (LMICs) have been much slower to do so due to a lack of funding, skilled healthcare providers, equipment, and facilities. The redistribution of resources to combat the pandemic in LMICs has resulted in decreased surgical volumes at local surgical centers as well as a dramatic reduction in the number of humanitarian aid missions. Despite recent global investment in improving the surgical capacities of LMICs, even in the pre-COVID-19 era there was a vast unmet surgical need.

Venous thromboembolism risk stratification in trauma using the Caprini risk assessment model.

Introduction: The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients.

Materials And Methods: We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018.

Total Transperineal Laparoscopic Proctectomy for the Treatment of Crohn's Proctitis.

Introduction: Completion proctectomy is traditionally performed using a combination of abdominal and perineal approaches. Access to and exposure of the pelvis through the abdominal cavity can be limited in patients with prior surgery or inflammatory conditions. We describe a novel technique for a total transperineal approach for proctectomy for Crohn's proctitis, avoiding technical challenges, risks, and recovery associated with abdominal surgery.

Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial.

Background: Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1 pathway presents as a potential treatment target. We assessed safety, tolerability, and preliminary efficacy of BVS857, an IGF-1 mimetic, in patients with spinal and bulbar muscular atrophy.

Nucleocytoplasmic transport defect in a North American patient with ALS8.

Amyotrophic lateral sclerosis 8 (ALS8) is a rare progressive neurodegenerative disease resulting from mutation in the gene for vesicle-associated membrane protein-associated protein B. We evaluated a North American patient using exome sequencing, and identified a P56S mutation. The disease protein had similar subcellular localization and expression levels in the patient and control fibroblasts.

Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression.

Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy.

Objective: To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA).

Methods: Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging.

Patient-identified impact of symptoms in spinal and bulbar muscular atrophy.

Introduction: The effects of spinal bulbar muscular atrophy (SBMA) on quality of life (QoL) are not well understood. This study describes symptoms from the patient's perspective and the impact these symptoms have on QoL.

Methods: We conducted open-ended interviews with 21 adult men with genetically confirmed SBMA.

IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation.

Endoplasmic reticulum (ER)-associated degradation (ERAD) represents a principle quality control mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unexplored. Here we discover that IRE1α, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. ERAD-mediated IRE1α degradation occurs under basal conditions in a BiP-dependent manner, requires both the intramembrane hydrophilic residues of IRE1α and the lectin protein OS9, and is attenuated by ER stress.

The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and lipid metabolism.

Sel1L is an essential adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum (ER)-associated degradation (ERAD), a universal quality-control system in the cell; but its physiological role remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Further analyses reveal that Sel1L is indispensable for the secretion of lipoprotein lipase (LPL), independent of its role in Hrd1-mediated ERAD and ER homeostasis.