Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.

The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.

Psychiatrists' Experiences, Training Needs, and Preferences Regarding Prescription and Management of HIV Pre-exposure Prophylaxis (PrEP) Within Psychiatric Care.

Background: People living with mental illness (PLWMI) experience a disproportionate prevalence and incidence of HIV. Preventing HIV among PLWMI is a priority for multiple domestic public health agencies. As key clinicians for this group, psychiatrists may have an important role to play in increasing PrEP use among PLWMI.

Commentary: The Effect of Corticosteroid Injection in the Treatment of Greater Trochanter Pain Syndrome.

Greater Trochanteric Pain Syndrome is a broad term employed to characterize lateral hip pain originating from the structures attached to the greater trochanter of the femur. The documented decrease in work participation, elevated levels of pain and dysfunction impeding physical activity, and diminished quality of life align with those observed in individuals with severe hip osteoarthritis. Effectively managing Greater Trochanteric Pain Syndrome can present considerable challenges.

Splenic marginal zone lymphoma with prolymphocytic transformation and cyclin D1 expression in the absence of CCND1 rearrangement.

Splenic marginal zone lymphoma (SMZL) is one of the most common B-cell lymphomas that affect the spleen. We report a case with splenomegaly and lymphocytosis that showed a clonal B-cell population lacking CD5 and CD10 expression. Notably, the atypical lymphoid cells showed prolymphocytoid morphology and expressed cyclin D1.

Flow cytometry assay modifications: Recommendations for method validation based on CLSI H62 guidelines.

The Clinical and Laboratory Standards Institute (CLSI) H62-Validation of Assays Performed by Flow Cytometry guideline, released in 2021, provides recommendations for platform workflow and quality system essentials, instrument setup and standardization, assay development and optimization and fit-for-purpose analytical method validation. In addition, CLSI H62 includes some recommendations for the validation strategies after a validated flow cytometric method has been modified. This manuscript builds on those recommendations and discusses the impact of different types of assay modifications on assay performance.

RHNO1: at the crossroads of DNA replication stress, DNA repair, and cancer.

The DNA replication stress (DRS) response is a crucial homeostatic mechanism for maintaining genome integrity in the face of intrinsic and extrinsic barriers to DNA replication. Importantly, DRS is often significantly increased in tumor cells, making tumors dependent on the cellular DRS response for growth and survival. Rad9-Hus1-Rad1 Interacting Nuclear Orphan 1 (RHNO1), a protein involved in the DRS response, has recently emerged as a potential therapeutic target in cancer.

Application in Parallel to U.S. Residency Training Programs in Multiple Specialties: Trends and Differences by Applicant Educational Background, 2009-2021.

Purpose: The medical education community is pursuing reforms addressing unsustainable growth in the number of residency applications per applicant and application costs. Little research has examined the prevalence or contributions of parallel applications (application to residency in multiple specialties) to this growth.

Method: A retrospective analysis of Electronic Residency Application Service® data provided by the Association of American Medical Colleges was conducted.

Addressing the Gap: Racial Disparities and Public Health Strategies in the Epidemiology of Gastrointestinal Stromal Tumors.

Background Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal neoplasms of the gastrointestinal tract, arising from the interstitial cells of Cajal. These tumors bridge the nervous system and muscular layers of the gastrointestinal tract, playing a crucial role in the digestive process. The incidence of GISTs demonstrates notable variations across different racial and ethnic groups, underscoring the need for in-depth analysis to understand the interplay of genetic, environmental, and socioeconomic factors behind these disparities.

Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021.

To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP). We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP.

Psychiatry and Family Medicine Residents' Likelihood of Prescribing HIV Pre-exposure Prophylaxis to Patients With Mental Illness and HIV Vulnerability.

Background: People living with mental illness (PLMI) experience disproportionately high incidence of and vulnerability to HIV. Pre-exposure prophylaxis (PrEP) is an effective and safe HIV prevention method, but data regarding prescription to PLMI are lacking. Psychiatrists may serve as important points of access for PrEP prescription for PLMI.

RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.

The mammalian SUMO-targeted E3 ubiquitin ligase Rnf4 has been reported to act as a regulator of DNA repair, but the importance of RNF4 as a tumor suppressor has not been tested. Using a conditional-knockout mouse model, we deleted Rnf4 in the B cell lineage to test the importance of RNF4 for growth of somatic cells. Although Rnf4-conditional-knockout B cells exhibited substantial genomic instability, Rnf4 deletion caused no increase in tumor susceptibility.

Parallel Application to U.S. Psychiatry Residency Programs: Trends in Frequency and Differences by Applicant Group, 2009-2021.

Objective: The present study examines trends of percent of applicants, number of specialties, and specialty combinations for psychiatry residency applicants applying to multiple specialties (parallel application).

Methods: The authors conducted a retrospective analysis of data captured by the Association of American Medical Colleges Electronic Residency Application System for applicants to psychiatry residency between 2009 and 2021. The percent parallel-applying, the mean number of specialties, mean application counts, and frequency of specialty combinations with psychiatry residency were determined.

Understanding the Landscape: The Emergence of Artificial Intelligence (AI), ChatGPT, and Google Bard in Gastroenterology.

Introduction Artificial intelligence (AI) integration in healthcare, specifically in gastroenterology, has opened new avenues for enhanced patient care and medical decision-making. This study aims to assess the reliability and accuracy of two prominent AI tools, ChatGPT 4.0 and Google Bard, in answering gastroenterology-related queries, thereby evaluating their potential utility in medical settings.

An Atypical relapsing follicular lymphoma to composite Hodgkin's lymphoma.

Composite lymphoma is defined as two or more lymphomas with distinct morphological and immunophenotypical characteristics synchronously diagnosed at the same anatomical site. Composite lymphoma is rare, and the most common combination is follicular lymphoma (FL) associated with diffuse large B cell lymphoma, followed by FL associated with classic Hodgkin's lymphoma (HL). Histologically, composite lymphomas display a mixed pattern or distinct zonal distribution of each lymphoma component.

Prophylactic Prednisolone Promotes AAV5 Hepatocyte Transduction Through the Novel Mechanism of AAV5 Coreceptor Platelet-Derived Growth Factor Receptor Alpha Upregulation and Innate Immune Suppression.

Adeno-associated virus (AAV) vectors are used to deliver therapeutic transgenes, but host immune responses may interfere with transduction and transgene expression. We evaluated prophylactic corticosteroid treatment on AAV5-mediated expression in liver tissue. Wild-type C57BL/6 mice received 6 × 10 vg/kg AAV5-HLP-hA1AT, an AAV5 vector carrying a human α1-antitrypsin (hA1AT) gene with a hepatocyte-specific promoter.

Graduate Medical Education Curriculum Regarding the Health and Healthcare of Older Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ+) Adults.

Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) adults experience a wide variety of unique challenges accessing healthcare. These barriers may be exacerbated among older LGBTQ+ people due to intersecting, marginalized identities. To prepare physicians to address the healthcare needs of older LGBTQ+ adults, graduate medical education (GME) must include training about the specific needs of this population.

Examination of Incidence of Sexually Transmitted Infections in the Ending the HIV Epidemic Priority Counties of the United States, 2005-2019.

Background: The incidence of sexually transmitted infections (STIs) has been increasing in the United States, and this trend has continued alongside expanding/changing human immunodeficiency virus (HIV) prevention strategies, moving from reliance solely on behavioral interventions like condoms to biomedical methods like oral and injectable antiretroviral preexposure prophylaxis (PrEP). In 2019, the Ending the HIV Epidemic (EHE) initiative was released to prioritize resource allocation to the 50 jurisdictions in the United States with the highest HIV incidence, providing an opportunity to monitor STI incidence in a national group of discrete, geographic units and identify trends and differences across jurisdictions.

Objectives And Design: Using existing data from the US CDC and Census Bureau, a retrospective analysis was conducted to examine the incidence of STIs in 49 of the 50 EHE priority counties between 2005 and 2019.

Availability of Testing for Sexually Transmitted Infections and HIV in U.S. Outpatient Mental Healthcare Settings.

People with mental illnesses experience higher incidence of sexually transmitted illnesses (STIs) and HIV, and estimates show fewer than 50% have received testing. The purpose of this study was to examine the prevalence of STI/HIV testing among United States outpatient mental healthcare service providers. Data from the National Mental Health Services Survey (NMHSS) was used to determine the rates of STI and HIV testing amongst 9,267 outpatient mental healthcare service providers in the U.

Secondary Pure Red Cell Aplasia During Daratumumab/ Hyaluronidase Therapy for Multiple Myeloma.

Predominantly autoimmune in origin, severe normochromic, normocytic anemia with reticulocytopenia in the setting of the normal production of leukocytes and megakaryocytic lineages is known as pure red cell aplasia (PRCA), which is unlike aplastic anemia in which all lineages are affected due to a stem cell defect. PRCA can be primary (such as autoimmune) or acquired, which can be an acute self-limited illness or a chronic disease that may be induced by medications, including immunotherapy such as monoclonal antibodies (mAbs). Daratumumab is a mAb directed against CD38 used for the treatment of multiple myeloma and systemic amyloid light-chain amyloidosis.

An Adult With Undifferentiated Embryonal Sarcoma of the Liver: A Case Report of a Rare Encounter.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare, aggressive tumor mainly found in children but can also appear in adults. Its diagnosis in adults remains a conundrum; it is often identified late due to its non-specific symptoms and resemblance to benign lesions. A comprehensive treatment regimen involving surgical intervention, chemotherapy, and possibly radiation significantly boosts survival rates.

Unpacking the Racial Gap: Helicobacter pylori Infection Clearance Among Different Racial Groups.

Introduction Helicobacter pylori (H. pylori) is a bacteria causing chronic stomach infections, influenced by various factors, including host traits and bacterial virulence. It uses both urease-dependent and independent mechanisms to survive acidic gastric environments.

Acceptability and Effectiveness of a One-Hour Healthcare Provider Intervention Integrating HIV Pre-Exposure Prophylaxis and Cultural Competence Training.

Enhanced provider training could improve PrEP access and equity. We conducted a pilot randomized controlled trial comparing (a) a one-hour, group-based provider intervention integrating PrEP and Cultural Competence (PCC) training with (b) a standard HIV continuing medical education session (n = 56). PCC participants favorably rated the intervention and reported increased PrEP knowledge.

The Path to Sustainable Healthcare: Implementing Care Transition Teams to Mitigate Hospital Readmissions and Improve Patient Outcomes.

Introduction Hospital readmissions within 30 days suggest care quality issues and increased mortality risks. They result from ineffective initial treatment, poor discharge planning, and inadequate post-acute care. These high readmission rates harm patient outcomes and financially strain healthcare institutions, inviting penalties and discouraging potential patients.