Adeno-Associated Virus (AAV)-Delivered Exosomal TAT and BiTE Molecule CD4-αCD3 Facilitate the Elimination of CD4 T Cells Harboring Latent HIV-1.

Combinatorial antiretroviral therapy (cART) has transformed HIV infection from a death sentence to a controllable chronic disease, but cannot eliminate the virus. Latent HIV-1 reservoirs are the major obstacles to cure HIV-1 infection. Previously, we engineered exosomal Tat (Exo-Tat) to reactivate latent HIV-1 from the reservoir of resting CD4+ T cells.

Evaluating Child Passenger Restraint Use Education.

Background: Despite recommendations and laws for child restraint use in motor vehicles, evidence of low restraint use remains, and there is a lack of evidence addressing the effectiveness of restraint use education.

Objective: This project aims to measure the impact of an education initiative on child passenger restraint use.

Methods: This pre- and postintervention study was conducted in six elementary schools in a Southwestern U.

GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that has been implicated in numerous oncogenic processes. GSK-3 inhibitor elraglusib (9-ING-41) has shown promising preclinical and clinical antitumor activity across multiple tumor types. Despite promising early-phase clinical trial results, there have been limited efforts to characterize the potential immunomodulatory properties of elraglusib.

GSK-3 inhibitor elraglusib enhances tumor-infiltrating immune cell activation in tumor biopsies and synergizes with anti-PD-L1 in a murine model of colorectal cancer.

Unlabelled: Inhibition of GSK-3 using small-molecule elraglusib has shown promising preclinical antitumor activity. Using in vitro systems, we found that elraglusib promotes immune cell-mediated tumor cell killing, enhances tumor cell pyroptosis, decreases tumor cell NF-κB-regulated survival protein expression, and increases immune cell effector molecule secretion. Using in vivo systems, we observed synergy between elraglusib and anti-PD-L1 in an immunocompetent murine model of colorectal cancer.

Autophagy augmentation alleviates cigarette smoke-induced CFTR-dysfunction, ceramide-accumulation and COPD-emphysema pathogenesis.

In this study, we aimed to investigate precise mechanism(s) of sphingolipid-imbalance and resulting ceramide-accumulation in COPD-emphysema. Where, human and murine emphysema lung tissues or human bronchial epithelial cells (Beas2b) were used for experimental analysis. We found that lungs of smokers and COPD-subjects with increasing emphysema severity demonstrate sphingolipid-imbalance, resulting in significant ceramide-accumulation and increased ceramide/sphingosine ratio, as compared to non-emphysema/non-smoker controls.

Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis.

Background: Cystic Fibrosis (CF) is a genetic disorder caused by mutation(s) in the CF-transmembrane conductance regulator (Cftr) gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa), a common CF pathogen, exacerbates obstructive CF lung pathology.

Augmentation of S-Nitrosoglutathione Controls Cigarette Smoke-Induced Inflammatory-Oxidative Stress and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis by Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function.

Aims: Cigarette smoke (CS)-mediated acquired cystic fibrosis transmembrane conductance regulator (CFTR)-dysfunction, autophagy-impairment, and resulting inflammatory-oxidative/nitrosative stress leads to chronic obstructive pulmonary disease (COPD)-emphysema pathogenesis. Moreover, nitric oxide (NO) signaling regulates lung function decline, and low serum NO levels that correlates with COPD severity. Hence, we aim to evaluate here the effects and mechanism(s) of S-nitrosoglutathione (GSNO) augmentation in regulating inflammatory-oxidative stress and COPD-emphysema pathogenesis.

Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis.

Aims: Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study, we aimed to evaluate the role of master autophagy transcription factor EB (TFEB) in CS-induced COPD-emphysema pathogenesis.

Results: We first observed that TFEB accumulates in perinuclear spaces as aggresome-bodies in COPD lung tissues of tobacco smokers and severe emphysema subjects, compared with non-emphysema or nonsmoker controls.

Surgical treatment of os acromiale with and without associated rotator cuff tears.

Nineteen consecutive patients treated surgically for meso-os acromiale and subacromial pathology were reviewed retrospectively, with a mean length of follow-up of 40 months (range, 24-94 months). Of the patients, 11 (58%) were treated with acromioplasty in the presence of a stable os acromiale; 8 patients (42%) underwent open reduction-internal fixation for an unstable and painful os fragment. Of the 19 patients, 8 (42%) with an os acromiale had an associated full-thickness rotator cuff tear.

Arthroscopy effectively treats ganglion cysts of the shoulder.

Unlabelled: In the hands of an experienced arthroscopist, arthroscopic decompression of a spinoglenoid notch cyst can lead to resolution of a patient's symptoms and complete functional recovery. In our study, we hypothesized that patients with a spinoglenoid notch cyst who were treated arthroscopically would have return to near normal function of their shoulders and that the outcomes for patients with a spinoglenoid notch cyst and associated labral tears would be no different than the outcomes for patients with a spinoglenoid notch cyst without associated labral tears. We retrospectively evaluated 18 consecutive patients who were treated arthroscopically for a spinoglenoid notch cyst.

In vitro analysis of antifungal impregnated polymethylmethacrylate bone cement.

Fungal infection is a rare but devastating complication of total joint arthroplasty. Many patients require removal of the components and resection arthroplasty for cure; however, revision arthroplasty with medicated polymethylmethacrylate bone cement may be used to salvage the joint. Some studies have documented the efficacy of mixing antibiotics with polymethylmethacrylate, but the efficacy of antifungal drugs when mixed with polymethylmethacrylate is unknown.