Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.

Streptococcal pyogenic exotoxins (Spe proteins) secreted by (group A , GAS) are responsible for scarlet fever and streptococcal toxic shock syndrome. Most Spes are superantigens that cause excessive inflammation by activating large numbers of T cells. However, Streptococcal pyogenic exotoxin B (SpeB) is an exception, which is pro-inflammatory through its protease activity.

Cervical cancer stage distribution and survival outcomes in Africa: a systematic review and meta-analysis.

Objective: Cervical cancer is a leading cause of cancer-related deaths among women, with a disproportionate burden in sub-Saharan Africa. Understanding the cervical cancer stage and outcomes is crucial for developing effective interventions and reducing its burden. We aimed to undertake a systematic review and meta-analysis of cervical cancer stage distribution and survival outcomes in Africa.

PP2A Attenuates Thoracic Aneurysm and Dissection in Mouse Models of Marfan Syndrome.

Background: Recent studies show that hyperactivation of mTOR (mammalian target of rapamycin) signaling plays a causal role in the development of thoracic aortic aneurysm and dissection. Modulation of PP2A (protein phosphatase 2A) activity has been shown to be of significant therapeutic value. In light of the effects that PP2A can exert on the mTOR pathway, we hypothesized that PP2A activation by small-molecule activators of PP2A could mitigate AA progression in Marfan syndrome (MFS).

ALS Motor Observational Telemedicine Objective Rasch-Built Assessment: A Quantitative Scale for the Era of Teleneurology.

Background And Objectives: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.

Methods: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors.

Capture of Patient Itch Scores in Practice Reveals Disparate Itch Impact on the Basis of Age, Gender, and Race: A Cross-Sectional Survey Analysis.

Background: Skin symptom burden, varying with patient populations, may not be readily observed by clinicians, resulting in incomplete appreciation of total skin disease burden.

Objective: The purpose of this study was to define patient itch burdens and associated health-related QOL affecting different patient demographics and to identify potential population health disparities.

Methods: This is a cross-sectional, secondary data analysis of data captured using an automated routine electronic previsit survey completed by patients who visited Emory Healthcare Dermatology clinic between March 2021 and October 2022 (6532 patient visits).

Sexual identity, sexual behavior, and drug use behaviors among people who use drugs in the rural U.S.

Introduction: People who use drugs (PWUD) are at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within rural communities is not well understood. Further, while interventions designed to more explicitly affirm individuals' sexual orientation and behaviors may be more effective, descriptions of behavior variability by orientation are lacking. We sought to describe how disease transmission behaviors and overdose risk vary by sexual orientation and activity among rural PWUD.

Longitudinal Associations of PFAS Exposure With Insulin Sensitivity and β-Cell Function Among Hispanic Women With Gestational Diabetes Mellitus History.

Objective: We investigated associations between per- and polyfluoroalkyl substances (PFAS) and changes in diabetes indicators from pregnancy to 12 years after delivery among women with a history of gestational diabetes mellitus (GDM).

Research Design And Methods: Eighty Hispanic women with GDM history were followed from the third trimester of pregnancy to 12 years after delivery. Oral and intravenous glucose tolerance tests were conducted during follow-up.

Demographic, medical, and neighborhood barriers to clinical neuropsychological services in pediatric medulloblastoma patients treated in the United States.

Background: Medulloblastoma is the most commonly occurring malignant brain tumor of childhood. Treatment includes a combination of surgery, radiation therapy, and chemotherapy, all of which are associated with cognitive impairments. Despite appreciation of the value of neuropsychological evaluations to assess for cognitive impairments, there are barriers to these evaluations.

Restoring cefepime activity against multidrug-resistant KPC-producing by combination with boronic acid inhibitors, MB076 and S02030.

Foremost in the design of new β-lactamase inhibitors (BLIs) are the boronic acid transition state inhibitors (BATSIs). Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of expressing a variety of class A and class C β-lactamases, including and .

Policy Recommendations to Support Equitable Access to Long-Acting Injectables for Human Immunodeficiency Virus Prevention and Treatment: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured.

Social epidemiology of early adolescent nutrition.

Background: This study aimed to investigate associations between sociodemographic factors and dietary intake among a diverse population of early adolescents ages 10-13 years in the United States.

Methods: We examined data from the Adolescent Brain Cognitive Development (ABCD) Study in Year 2 (2018-2020, ages 10-13 years, N = 10,280). Multivariable linear regression models were conducted to estimate the adjusted associations between sociodemographic factors (age, sex, race and ethnicity, household income, parental education) and dietary intake of various food groups, measured by the Block Kids Food Screener.

Patterns in progression from early-stage melanoma to late-stage melanoma: implications for survivorship follow-up.

This study determined the characteristics of patients with early-stage melanoma (IA-IIA) who later had stage IV recurrence. We retrospectively examined 880 melanoma patients and identified those who progressed to stage IV disease from an initial early-stage (n = 50). We observed a median latent period of 4 years between early-stage diagnosis and metastatic disease.

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC.

Impact of molecular diagnostic techniques on the acute respiratory infection sentinel surveillance program, Antioquia, Colombia, 2022.

Objectives: Surveillance of acute respiratory infection (ARI) informs vaccination, preventive, and management decisions. In many countries, immunofluorescence is the cornerstone for ARI surveillance. We aimed to determine the effect of adding multiplex polymerase chain reaction (mPCR) to conventional surveillance in ARI.

Optimizing care for gastric cancer with overt bleeding: Is systemic therapy a valid option?

Gastric cancer (GC) and gastroesophageal junction cancer (GEJC) represent a significant burden globally, with complications such as overt bleeding (OB) further exacerbating patient outcomes. A recent study by Yao evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB. Using propensity score matching, the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.

The PIKASO trial (Preventing Injured Knees from Osteoarthritis: Severity Outcomes): Rationale and design features for a randomized controlled trial.

Objective: Given the high burden and increasing prevalence of post-traumatic osteoarthritis (PTOA), identifying clinically beneficial strategies to prevent or delay its onset could improve the quality of life of those at high risk of developing the disease.

Methods: Preventing Injured Knees from OsteoArthritis: Severity Outcomes (PIKASO) is a multicenter blinded, parallel, two-arm randomized controlled trial of 512 individuals aged 18-45 years undergoing anterior cruciate ligament reconstruction (ACLR). This study is designed to evaluate the efficacy of a 12-month intervention of oral metformin vs.

Understanding the opioid syndemic in North Carolina: A novel approach to modeling and identifying factors.

The opioid epidemic is a significant public health challenge in North Carolina, but limited data restrict our understanding of its complexity. Examining trends and relationships among different outcomes believed to reflect opioid misuse provides an alternative perspective to understand the opioid epidemic. We use a Bayesian dynamic spatial factor model to capture the interrelated dynamics within six different county-level outcomes, such as illicit opioid overdose deaths, emergency department visits related to drug overdose, treatment counts for opioid use disorder, patients receiving prescriptions for buprenorphine, and newly diagnosed cases of acute and chronic hepatitis C virus and human immunodeficiency virus.

HIV co-infection is associated with increased HLA-DR expression by Mycobacterium tuberculosis-specific CD4 T cells in people with latent tuberculosis infection.

Infection with HIV is associated with dysregulated CD4 T cell responses to Mycobacterium tuberculosis (Mtb) and increased risk of developing tuberculosis. Mtb-specific CD4 T cells in people with HIV have diminished Th1 cytokine production capacity, thus we utilized a flow cytometry-based assay to measure CD40L expression by Mtb-specific CD4 T cells in a cytokine-independent manner. We evaluated the frequency and phenotype of Mtb-specific CD4 responses in Kenyan adults with latent Mtb infection and found that the majority of Mtb-specific CD4 T cells expressed CD40L in the absence of IFN-γ, regardless of HIV infection status.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.