Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Alteplase Purge Solution for Impella 5.5 Ventricular Assist Device Purge System Occlusion: Case Report and Review of the Literature.

The use of an alteplase (Activase) purge solution to address Impella ventricular assist device "thrombosis" or "purge system occlusion" has been mainly documented with earlier generation Impella devices (CP, 2.5, 5.0).

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Association Between Symptoms of Body Dysmorphia and Social Media Usage: A Cross-Generational Comparison.

The rise of social media parallels a mental health epidemic. The effect of social media usage on rates and severity of body dysmorphic disorder is not well-understood. To determine if an association exists between social media engagement, body dysmorphia symptoms, and/or interest in cosmetic surgery in a demographically diverse cross-section of the U.

Role of tRNA-Derived Fragments in Protozoan Parasite Biology.

tRNA molecules are among the most fundamental and evolutionarily conserved RNA types, primarily facilitating the translation of genetic information from mRNA into proteins. Beyond their canonical role as adaptor molecules during protein synthesis, tRNAs have evolved to perform additional functions. One such non-canonical role for tRNAs is through the generation of tRNA-derived fragments via specific cleavage processes.

Synthesizing the Evidence Base to Enhance Coordination between Humanitarian Mine Action and Emergency Care for Casualties of Explosive Ordnance and Explosive Weapons: A Scoping Review.

Background: Humanitarian mine action (HMA) stakeholders have an organized presence with well-resourced medical capability in many conflict and post-conflict settings. Humanitarian mine action has the potential to positively augment local trauma care capacity for civilian casualties of explosive ordnance (EO) and explosive weapons (EWs). Yet at present, few strategies exist for coordinated engagement between HMA and the health sector to support emergency care system strengthening to improve outcomes among EO/EW casualties.

Temporal Trends of Fungal Infections in Cirrhotic Patients: A Retrospective Cohort Study 2016-2020.

Background: Patients with cirrhosis are susceptible to infections due to abnormalities in humoral and cell-mediated immunity. Fungal infections are associated with delayed diagnosis and high mortality rates, emphasizing the importance of performing fungal cultures and maintaining elevated levels of suspicion in this patient population.

Methods: This retrospective cohort study analyzes cirrhotic patients readmitted with bacterial and fungal infections and investigates outcomes, including in-hospital mortality and hospital resource utilization.

Advancing precision cancer immunotherapy drug development, administration, and response prediction with AI-enabled Raman spectroscopy.

Molecular characterization of tumors is essential to identify predictive biomarkers that inform treatment decisions and improve precision immunotherapy development and administration. However, challenges such as the heterogeneity of tumors and patient responses, limited efficacy of current biomarkers, and the predominant reliance on single-omics data, have hindered advances in accurately predicting treatment outcomes. Standard therapy generally applies a "one size fits all" approach, which not only provides ineffective or limited responses, but also an increased risk of off-target toxicities and acceleration of resistance mechanisms or adverse effects.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

Lung injury in myocardial infarction-associated cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation: a scoping review.

Background: Acute lung injury and acute respiratory failure are frequent complications of cardiogenic shock and are associated with increased morbidity and mortality. Even with increased use of temporary mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), acute lung injury related to cardiogenic shock continues to have a determinantal effect on patient outcomes.

Objectives: To summarize potential mechanisms of acute lung injury described in patients with cardiogenic shock supported by VA-ECMO and determine current knowledge gaps.

Unbound bilirubin and risk of severe neurodevelopmental impairment in extremely low birthweight newborns.

Background: Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.

Methods: UB levels were standardized within laboratories as z-score percentiles.

The relationship between cannabis and cardiovascular disease: clearing the haze.

Cannabis has been consumed for centuries, but global regulatory changes over the past three decades have increased the availability and consumption of cannabis. Cannabinoids are touted to have therapeutic potential for many diseases and could be a replacement for opioids for analgesia and sedation. However, cannabinoids can cause substantial adverse cardiovascular events that would mitigate any potential benefit.

Relationships between structural stigma, societal stigma, and minority stress among gender minority people.

Structural stigma towards gender minority (GM; people whose current gender does not align with sex assigned at birth) people is an important contributor to minority stress (i.e., stress experienced due to one's marginalized GM identity), although existing variables are unclear in their inclusion of social norms, or societal stigma, as a key component of the construct.

The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.

Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.

Background: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.

Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

The family's role in mental health care: Perceptions of Bay Area Muslims.

This qualitative study examines perceptions of Muslims living in the San Francisco Bay Area, California, United States, regarding the family's role in mental health help-seeking and well-being. This study employed a community-based participatory research approach through content analysis of three focus group ( = 37) discussions conducted with the help of a community advisory board comprised San Francisco Bay Area Muslim community members. Four main themes were generated.

Early Motor Signs in Pathologically Verified Alzheimer's Disease and Lewy Body Disease.

Background: The neuropathologies of Alzheimer's disease (AD) and Lewy body disease (LBD) commonly co-occur. Parkinsonism is the hallmark feature in LBD but it can be difficult to predict the presence of these co-pathologies early in the course of clinical disease. Timely diagnosis has crucial implications, especially with the advent of disease-modifying therapies.

Varied terminology by radiologists to describe Bosniak class III and IV cystic renal masses.

Background: The Bosniak classification is designed to standardize evaluation of cystic renal masses and to communicate the risk of malignancy.

Purpose: To determine whether radiologists vary in their communication of Bosniak class III and IV cystic renal masses.

Material And Methods: This retrospective study included 186 patients with CT or MRI reporting a Bosniak class III or IV mass.