Mechanism-based approach in designing patient-specific combination therapies for nonsense mutation diseases.

Premature termination codon (PTC) diseases, arising as a consequence of nonsense mutations in a patient's DNA, account for approximately 12% of all human disease mutations. Currently there are no FDA approved treatments for increasing PTC readthrough in nonsense mutation diseases, although one translational readthrough inducing drug, ataluren, has had conditional approval for treatment of Duchenne muscular dystrophy in Europe and elsewhere for 10 years. Ataluren displays consistent low toxicity in clinical trials for treatment of several different PTC diseases, but its therapeutic effects on such diseases are inconsistent.

Antagonistic Effects of Actin-Specific Toxins on Typhimurium Invasion into Mammalian Cells.

Competition between bacterial species is a major factor shaping microbial communities. It is possible but remains largely unexplored that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. Using Typhimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by actin-specific toxins, namely, MARTX actin crosslinking (ACD) and Rho GTPase inactivation (RID) domains, TccC3, and 's own SpvB.

Women in Dental Clinical and Translational Research.

This article presents a summary of the third American Association for Dental, Oral, and Craniofacial Research Meeting within a Meeting, which was held during the 2024 annual meeting in New Orleans, Louisiana. Speakers were challenged to reflect on how women are differentially affected by health and societal issues by factors that go beyond biology. The goal was to promote current research on women's issues that are relevant to dental, oral, and craniofacial scientists.

Stigma-associated attitudes and practices among Romanian clinical providers.

Objectives: People living with HIV/AIDS today expect a typical lifespan, although many continue to encounter psychological and societal challenges, including stigma and discrimination. In healthcare settings, this may manifest as refusal of care or treatment, non-consensual testing, confidentiality breaches, and unfavourable attitudes, among other issues. We sought to better understand stigma-related beliefs and practices within the Romanian clinician community.

The Rochester Model for Spinal CSF Leak Repair Simulation and Scoring.

Background And Objective: Iatrogenic spinal durotomies occur at a rate of 1% to 17%. Surgical simulation for durotomy repair is needed to provide affordable, accessible, and validated practice. This study sought to design and validate a simple 3-dimensional printed model for spinal cerebrospinal fluid (CSF) leak repair and to introduce the Rochester original objective structured assessment of technical skills (OSATS) CSF leak (ROCL) repair criteria for assessment.

Disparities in Breast Cancer Treatment and Reconstruction Among Native Hawaiian and Pacific Islander Women: Systematic Review and Meta-Analysis.

Background: Native Hawaiian and Pacific Islander (NHPI) women experience significant disparities in breast cancer treatment and outcomes, including lower rates of postmastectomy reconstruction, higher refusal rates of radiation therapy, and delays in surgical care. These disparities contribute to poorer survival and increased complications compared to other racial/ethnic groups. This systematic review and meta-analysis aim to quantify these disparities and assess their impact on breast cancer outcomes in NHPI women.

Increases in PM levels in Houston are associated with a highly recirculating sea breeze.

Local land-sea breezes play an important role in coastal air quality because they circulate air between coastal/urban and marine areas, potentially causing the accumulation of pollutants. This has been observed for the secondary photochemical pollutant ozone. However, particulate matter (PM) also warrants investigation.

Sunscreen use associated with elevated prevalence of anti-nuclear antibodies in U.S. adults.

Background: Antinuclear antibody (ANA) prevalence in the U.S. population increased from 1988 to 2012, especially in white and more educated individuals.

Variability in Invasive Bacterial Infection Proportions Among Febrile Infants Aged 8-90 Days Using Administrative Data.

Objective: Despite decades of research, knowledge is limited regarding sociodemographic risk factors (eg, sex, rural/urban residence) for invasive bacterial infections (IBIs; bacteremia, bacterial meningitis) in young febrile infants and outcomes of current management strategies. Population-based administrative datasets can provide epidemiological insights not possible with clinical data but are limited because diagnosis codes alone may not accurately reflect culture-positive bacteremia or meningitis infections. Thus, using different IBI case definitions, we report IBI and missed IBI proportions in a population of febrile infants aged 8-90 days.

Performance of AAP CPG for Ineligible Well-Appearing Febrile Infants Aged 8-60 Days.

Background And Objectives: The AAP's Clinical Practice Guidelines (CPG) for febrile infants provides recommendations in evaluating well-appearing febrile infants aged 8-60 days at risk for invasive bacterial infections (IBIs; ie, bacteremia and bacterial meningitis). However, guidance remains limited for the infants excluded from (ie, ineligible for) the CPG. The objectives are to estimate the proportion of well-appearing CPG-ineligible febrile infants and to examine CPG performance in detecting IBIs for CPG-ineligible febrile infants.

Cyclic peptides targeting the SARS-CoV-2 programmed ribosomal frameshifting RNA from a multiplexed phage display library.

RNA provides the genetic blueprint for many pathogenic viruses, including SARS-CoV-2. The propensity of RNA to fold into specific tertiary structures enables the biomolecular recognition of cavities and crevices suited for the binding of drug-like molecules. Despite increasing interest in RNA as a target for chemical biology and therapeutic applications, the development of molecules that recognize RNA with high affinity and specificity represents a significant challenge.

Source apportionment of ultrafine particles in urban Europe.

There is a body of evidence that ultrafine particles (UFP, those with diameters ≤ 100 nm) might have significant impacts on health. Accordingly, identifying sources of UFP is essential to develop abatement policies. This study focuses on urban Europe, and aims at identifying sources and quantifying their contributions to particle number size distribution (PNSD) using receptor modelling (Positive Matrix Factorization, PMF), and evaluating long-term trends of these source contributions using the non-parametric Theil-Sen's method.

Tapinarof, an Aryl Hydrocarbon Receptor Ligand, Mitigates Fibroblast Activation in Thyroid Eye Disease: Implications for Novel Therapy.

Purpose: In thyroid eye disease (TED), activation and proliferation of orbital fibroblasts (OFs) promotes remodeling and causes an increase in the volume of orbital tissue. Platelet-derived growth factors (PDGFs) are elevated in TED and promote OF activation. The aryl hydrocarbon receptor (AHR), a ligand activated nuclear receptor, is important in regulating OF activation.

Comparative evaluation of human oral fibroblast proliferation on 3D-printed zirconia and silicon nitride as new ceramic materials for implant abutment.

Purpose: Cell adhesion and subsequent proliferation on material surfaces depend on the physical and chemical characteristics of the material. There is a lack of literature on human gingival fibroblast proliferation on comparatively newer additively manufactured materials like silicon nitride. This study focused on the physical characteristics of the materials with the aim to compare the adhesion and proliferation of human gingival fibroblasts on additively manufactured silicon nitride (AMSN) with additively manufactured zirconia, conventional milled titanium (MTi), and milled zirconia.

Identity Work: A Qualitative Study of Residents' Experiences Navigating Identity Struggles.

Introduction: Medical training traditionally holds a deterministic view of professional socialization wherein many medical learners struggle to construct a professional identity. Previous research has demonstrated the dysfunctional norms and conflicting ideologies that create identity struggle, disproportionally affecting women and individuals underrepresented in medicine. Symbolic interactionism can help explain identity struggles, emphasizing the influence of socio-contextual factors on identity construction.