Postoperative atrial fibrillation following cardiac surgery in severe obesity: the added value of waist circumference.

Introduction: Obesity is an independent risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) surgery. POAF in patients with severe obesity (body mass index [BMI] ≥ 35 kg/m) is less studied. Whether waist circumference (WC) improves prediction of POAF independently of BMI among patients with severe obesity remains unknown.

BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.

Background: Bone morphogenetic protein (BMP) signaling cascade is a phylogenetically conserved stem cell regulator that is aberrantly expressed in non-small cell lung cancer (NSLC) and leukemias. BMP signaling negatively regulates mitochondrial bioenergetics in lung cancer cells. The impact of inhibiting BMP signaling on mitochondrial bioenergetics and the effect this has on the survival of NSLC and leukemia cells are not known.

Rapid induction of allergen-blocking IgG in dogs vaccinated with plant-based, Der f 2-expressing bioparticles.

Background: Allergen-carrying virus-like particles are effective and safe means of allergen immunotherapy (AIT) in rodent models.

Objective: To study the development of allergen-blocking immunoglobulin (Ig)G in dogs injected with Der f 2-carrying enveloped plant-based bioparticles (eBPs).

Materials And Methods: Laboratory beagle dogs were injected intradermally (ID) or subcutaneously (SC) with Der f 2-eBP three times at 2-week intervals.

Fragment Screening to Identify Inhibitors Targeting Ribosome Binding of Shiga Toxin 2.

Shiga toxins are the main virulence factors of Shiga toxin producing (STEC) and . There is no effective therapy to counter the disease caused by these toxins. The A1 subunits of Shiga toxins bind the C-termini of ribosomal P-stalk proteins to depurinate the sarcin/ricin loop.

A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.

The global threat of multidrug-resistant Gram-negative bacterial pathogens necessitates the development of new and effective antibiotics. FtsZ is an essential and highly conserved cytoskeletal protein that is an appealing antibacterial target for new antimicrobial therapeutics. However, the effectiveness of FtsZ inhibitors against Gram-negative species has been limited due in part to poor intracellular accumulation.

Structure-Activity Relationship of a Pyrrole Based Series of PfPKG Inhibitors as Anti-Malarials.

Controlling malaria requires new drugs against . The cGMP-dependent protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite's life cycle. We defined the structure-activity relationship (SAR) of a pyrrole series for PfPKG inhibition.

Sex-Specific Cardiometabolic Determinants of Postoperative Atrial Fibrillation After Cardiac Surgery.

Background: Cardiometabolic diseases increase the risk of postoperative atrial fibrillation (POAF), a complication leading to higher long-term risk of major cardiovascular events (MACE). It remains unknown whether the effect of these risk factors differs according to sex. We sought to evaluate the sex-specific predictors of POAF after coronary artery bypass grafting (CABG).

Structure-based design and optimization of a new class of small molecule inhibitors targeting the P-stalk binding pocket of ricin.

Ricin, a category-B agent for bioterrorism, and Shiga toxins (Stxs), which cause food poisoning bind to the ribosomal P-stalk to depurinate the sarcin/ricin loop. No effective therapy exists for ricin or Stx intoxication. Ribosome binding sites of the toxins have not been targeted by small molecules.

Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo.

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP.

A novel peanut allergy immunotherapy: Plant-based enveloped Ara h 2 Bioparticles activate dendritic cells and polarize T cell responses to Th1.

Introduction: As the only market-authorized allergen immunotherapy (AIT) for peanut allergy is accompanied by a high risk of side effects and mainly induces robust desensitization without sustained efficacy, novel treatment options are required. Peanut-specific plant-derived Bioparticles (BPs) surface expressing Ara h 2 at high density have been shown to be very hypoallergenic. Here, we assessed the dendritic cell (DC)-activating and T cell polarization capacity of these peanut-specific BPs.

Acylpyrazoline-Based Third-Generation Selective Antichlamydial Compounds with Enhanced Potency.

Chlamydiae are obligate intracellular Gram-negative bacteria and widespread pathogens in humans and animals. Broad-spectrum antibiotics are currently used to treat chlamydial infections. However, broad-spectrum drugs also kill beneficial bacteria.

Shuttle Peptide Delivers Base Editor RNPs to Rhesus Monkey Airway Epithelial Cells .

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, to improve base editor RNP delivery, we optimized S10 to derive the S315 peptide.

A Retrospective Evaluation of the Impacts of a Multidisciplinary Care Model for Managing Patients with Advanced Illness on Acute Care Utilization and Quality of Care at End of Life.

A home-based goal-concordant care model targeting patients with advanced illnesses may reduce acute care utilization and improve quality outcomes at end of life. Study aim was to determine impact of the Advanced Illness Management (AIM) program on end-of-life utilization and quality of care. A retrospective observational study design using propensity score fine stratum weighting methodologies was applied to decedent patients identified for AIM enrollment/eligibility in 2018 to 2019.

The Anticancer Drug Bleomycin Shows Potent Antifungal Activity by Altering Phospholipid Biosynthesis.

Invasive fungal infections are difficult to treat with limited drug options, mainly because fungi are eukaryotes and share many cellular mechanisms with the human host. Most current antifungal drugs are either fungistatic or highly toxic. Therefore, there is a critical need to identify important fungal specific drug targets for novel antifungal development.

Ym155 localizes to the mitochondria leading to mitochondria dysfunction and activation of AMPK that inhibits BMP signaling in lung cancer cells.

The imidazolium compound Ym155 was first reported to be a survivin inhibitor. Ym155 potently induces cell death of many types of cancer cells in preclinical studies. However, in phase II clinical trials Ym155 failed to demonstrate a significant benefit.

Bone morphogenetic protein inhibitors and mitochondria targeting agents synergistically induce apoptosis-inducing factor (AIF) caspase-independent cell death in lung cancer cells.

Background: Bone morphogenetic proteins (BMP) are evolutionarily conserved morphogens that are reactivated in lung carcinomas. In lung cancer cells, BMP signaling suppresses AMP activated kinase (AMPK) by inhibiting LKB1. AMPK is activated by mitochondrial stress that inhibits ATP production, which is enhanced 100-fold when phosphorylated by LKB1.

Bone morphogenetic protein signaling regulation of AMPK and PI3K in lung cancer cells and C. elegans.

Background: Bone morphogenetic protein (BMP) is a phylogenetically conserved signaling pathway required for development that is aberrantly expressed in several age-related diseases including cancer, Alzheimer's disease, obesity, and cardiovascular disease. Aberrant BMP signaling in mice leads to obesity, suggesting it may alter normal metabolism. The role of BMP signaling regulating cancer metabolism is not known.

TXH11106: A Third-Generation MreB Inhibitor with Enhanced Activity against a Broad Range of Gram-Negative Bacterial Pathogens.

The emergence of multi-drug-resistant Gram-negative pathogens highlights an urgent clinical need to explore and develop new antibiotics with novel antibacterial targets. MreB is a promising antibacterial target that functions as an essential elongasome protein in most Gram-negative bacterial rods. Here, we describe a third-generation MreB inhibitor (TXH11106) with enhanced bactericidal activity versus the Gram-negative pathogens , , , and compared to the first- and second-generation compounds A22 and CBR-4830, respectively.

Validation of desk-based audits using Google Street View to monitor the obesogenic potential of neighbourhoods in a pediatric sample: a pilot study in the QUALITY cohort.

Background: The suitability of geospatial services for auditing neighbourhood features relevant to pediatric obesity remains largely unexplored. Our objectives were to (i) establish the measurement properties of a desk-based audit instrument that uses Google Street View to assess street- and neighbourhood-level features relevant to pediatric obesity (QUALITY-NHOOD tool, the test method) and (ii) comment on its capacity to detect changes in the built environment over an 8-year period. In order to do so, we compared this tool with an on-site auditing instrument (the reference method).

Heart rate variability after bariatric surgery: The add-on value of exercise.

Purpose: To assess the impact of bariatric surgery and an added supervised exercise training programme on heart rate variability (HRV) in patients with severe obesity.

Methods: Fifty-nine patients who underwent bariatric surgery were randomised in the post-operative period to a 12-week supervised exercise training programme (moderate intensity combination aerobic/resistance exercise training programme) or a control group. Indices of HRV including time-domain, spectral-domain, and nonlinear parameters were measured preoperatively, and at 3, 6, and 12 months.

Synthesis and Structural Characterization of Ricin Inhibitors Targeting Ribosome Binding Using Fragment-Based Methods and Structure-Based Design.

Ricin toxin A subunit (RTA) is the catalytic subunit of ricin, which depurinates an adenine from the sarcin/ricin loop in eukaryotic ribosomes. There are no approved inhibitors against ricin. We used a new strategy to disrupt RTA-ribosome interactions by fragment screening using surface plasmon resonance.