Drug Development.

Background: Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder with limited treatment options. As it progresses, synapse degeneration is the most important feature contributing to cognitive dysfunction. Mitochondria supply synapses with ATP for neurotransmitter release and vesicle recycling and buffer calcium concentrations.

Methods for Studying Motor-Driven Viral DNA Packaging in Bacteriophages phi29, Lambda, and T4 via Single DNA Molecule Manipulation and Rapid Solution Exchange.

Viral DNA packaging is a required step in the assembly of many dsDNA viruses. A molecular motor fueled by ATP hydrolysis packages the viral genome to near crystalline density inside a pre-formed prohead shell in ~5 min at room temperature in vitro. We describe procedures for measuring the packaging of single DNA molecules into single viral proheads with optical tweezers.

Characterization of a novel SNP identified in Australian group A isolates derived from the M1 lineage.

Group A (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1 lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections. However, the basis for its evolutionary success is not yet fully understood.

[Female urinary incontinence - diagnostics and therapies].

Urinary incontinence is a common complaint of both general practitioners and specialists. An accurate basic diagnosis with a structured medical history and bladder diary, urine analysis, gynaecological examination including pelvic floor assessment and a full bladder cough test can be supplemented by sonography, cystoscopy and urodynamic testing. This will help to differentiate between the different types of urinary incontinence, such as urge incontinence, stress incontinence and overflow incontinence.

A conserved burn wound infection model for diverse pathogenic fungi.

Unlabelled: Secondary fungal infections represent a major complication following thermal injuries. However, the mechanisms of fungal colonization of burn tissue and how the host subsequently responds to fungi within this niche remain unclear. We have previously reported a zebrafish model of thermal injury that recapitulates many of the features of human burn wounds.

The Influence of Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility.

can cause invasive pulmonary aspergillosis (IPA). Fungicidal azoles and fungistatic caspofungin (CAS) are the first- and second-line therapies, respectively, used to treat IPA. Treatment of with CAS or micafungin induces the production of the oxylipin 5,8-diHODE by the fungal oxygenase PpoA.

Comparing Outcomes Between Advanced Practice Providers and Housestaff Teams in the Cardiac Intensive Care Unit.

Background: With an increasing demand for critical care expertise and limitations in intensivist availability, innovative staffing models, such as the utilization of advanced practice providers (APPs), have emerged.

Objectives: The purpose of the study was to compare patient outcomes between APP and housestaff teams in the cardiac intensive care unit (CICU).

Methods: This retrospective study, spanning March 2022 to July 2023, compares patient characteristics and outcomes between two CICU teams embedded in the same CICU at a large urban academic hospital: one staffed by housestaff and the other by APPs (80% physician assistants, 20% nurse practitioners) who each had approximately 1 to 2 years of experience in the CICU.

Association between psychopharmacotherapy and postpartum hemorrhage.

Background: Prior studies evaluating the relationship between psychopharmacotherapy (PPT), and postpartum hemorrhage (PPH) have yielded inconsistent findings. Clarifying this potential relationship is important for effective counseling and risk stratification.

Objectives: Our primary objective was to evaluate the association between prenatal exposure to PPT (any drug class) and the occurrence of PPH requiring transfusion of packed red blood cells (PPH+pRBC) after systematically adjusting for known hemorrhage risk factors at the time of admission for delivery.

Right Ventricular-Pulmonary Arterial Uncoupling as a Predictor of Invasive Hemodynamics and Normotensive Shock in Acute Pulmonary Embolism.

Right ventricular-pulmonary arterial coupling describes the relation between right ventricular contractility and its afterload and is estimated as the ratio of the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) by way of echocardiography. Whether TAPSE/PASP is reflective of invasive hemodynamics or occult shock in acute pulmonary embolism (PE) is unknown. This was a single-center retrospective study over a 3-year period of consecutive patients with PE who underwent mechanical thrombectomy and simultaneous pulmonary artery catheterization with echocardiograms performed within 24 hours before the procedure.

Enhancing vascular access planning in CKD: validating the 40% KFRE threshold for predicting ESKD in a French retrospective cohort study.

Background: Establishing the optimal timing for creating vascular access in patients with chronic kidney disease (CKD) is a critical and challenging aspect of patient management. The Kidney Disease: Improving Global Outcomes guidelines propose using a 40% 2-year threshold based on the Kidney Failure Risk Equation (KFRE) for this purpose. However, the effectiveness of this threshold compared with traditional methods, such as estimated glomerular filtration rate (eGFR), is not well-established.

GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18.

Neutrophils are critical for host defense against fungi. However, the short life span and lack of genetic tractability of primary human neutrophils has limited analysis of neutrophil-fungal interactions. Human induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) are a genetically tractable alternative to primary human neutrophils.

A New Life for Tionite Industrial Waste: Regeneration Strategy towards Photocatalytic Applications.

Industrial waste management is an urgent problem to solve possibly by recycling, reuse and recovery of resources. In this framework, the sludge of the TiO manufacturing, called tionite, is of certain interest because it contains metallic oxide-bearing impurities, dangerous to the environment. Hence, we propose a strategy to recover TiO from tionite, towards its effective re-use as a photocatalyst.

Inferior vena cava contrast reflux grade is associated with a reduced cardiac index in acute pulmonary embolism.

Background And Aims: Patients with intermediate-risk pulmonary embolism (PE) commonly present with a significantly reduced cardiac index (CI). However, the identification of this more severe profile requires invasive hemodynamic monitoring. Whether inferior vena cava (IVC) contrast reflux, as a marker of worse right ventricular function, can predict invasive hemodynamics has not been explored.

Mitigating health disparities by improving access to catheter-based therapies for vulnerable patients with acute pulmonary embolism.

Introduction: This study explores the implementation and outcomes of catheter-based thrombectomy (CBT) for acute pulmonary embolism (PE) within a safety-net hospital (SNH), addressing a critical gap in the literature concerning CBT in underserved and vulnerable populations.

Methods: This is a retrospective study of patients undergoing CBT between October 2020 and January 2024 at a SNH. The primary outcome was 30-day all-cause mortality.

Correction: Seo et al. A Timeline of Biosynthetic Gene Cluster Discovery in : From Characterization to Future Perspectives. 2024, , 266.

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Investigating group A antibiotic tolerance in necrotizing fasciitis.

Group A (GAS) necrotizing fasciitis (NF) is a difficult-to-treat bacterial infection associated with high morbidity and mortality despite extensive surgery and targeted antibiotic treatment. Difficult-to-treat infections are often characterized by the presence of bacteria surviving prolonged antibiotic exposure without displaying genetic resistance, referred to as persisters. In the present study, we investigated the presence of GAS persisters in tissue freshly debrided from patients as well as in an mouse model of NF and examined the phenomenon of antibiotic tolerance.

Social vulnerability and prenatal diagnosis.

Objectives: There are limited data on how neighborhood-level risk factors affect the likelihood of having prenatal diagnosis. Neighborhood social vulnerability can be quantified and ranked using the social vulnerability index (SVI), a tool that measures the cumulative effect of external stressors in the local environment that may affect health outcomes. The objective of the study was to determine the relationship between SVI and prenatal diagnosis among pregnant patients who received genetic counseling.

When Should Patients With Less Than 6 Months Sobriety Be Transplanted?

Alcoholic liver disease (ALD) and alcohol-induced deaths have increased dramatically over the last 2 decades. Patients are often referred to liver transplant programs critically ill with a life expectancy of less than 6 months. Historically, less than 6 months sobriety has been an absolute contraindication for transplant listing as ALD is stigmatized as a choice, as patients are responsible for their condition because they did not stop drinking.

Bioactivity-driven fungal metabologenomics identifies antiproliferative stemphone analogs and their biosynthetic gene cluster.

Introduction: Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways.

Metarhizium spp. encode an ochratoxin cluster and a high efficiency ochratoxin-degrading amidohydrolase revealed by genomic analysis.

Introduction: Ochratoxins (OTs) are worldwide regulated mycotoxins contaminating a variety of food-environment and agro-environment. Several Aspergillus and Pencillium species synthesize OTs from a six-gene biosynthetic gene cluster (BGC) to produce the highly toxic final product OTA. Although many studies on OTA-degrading enzymes were performed, high efficiency enzymes with strong stability are extremely needed, and the OTA degrading mechanism is poorly understood.

Cardiovascular autonomic and peripheral sensory neuropathy in women with obesity.

Introduction: A higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters.

Patients And Methods: In our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment.