Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy.

Temporal lobe epilepsy (TLE) is a type of focal epilepsy characterized by spontaneous recurrent seizures originating from the hippocampus. The epigenetic reprogramming hypothesis of epileptogenesis suggests that the development of TLE is associated with alterations in gene transcription changes resulting in a hyperexcitable network in TLE. DNA 5-methylcytosine (5-mC) is an epigenetic mechanism that has been associated with chronic epilepsy.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing.

Association of Pneumococcal Conjugate Vaccination With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Older Adult Recipients of Coronavirus Disease 2019 Vaccines: A Longitudinal Cohort Study.

Background: Pneumococcal carriage is associated with increased acquisition and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on coronavirus disease 2019 (COVID-19)-related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2.

Methods: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January 2021 and 31 December 2022 among recipients and nonrecipients of 13-valent PCV (PCV13) employing multiple strategies to mitigate bias from differential test-seeking behavior.

Blockade of Ca3 calcium channels and induction of G/G cell cycle arrest in colon cancer cells by gossypol.

Background And Purpose: Gastrointestinal tumours overexpress voltage-gated calcium (Ca3) channels (Ca3.1, 3.2 and 3.

Improving Health Outcomes for African American Men with Kidney Disease: A Patient-Centered Approach to Cultural Competence.

In the United States, African American (AA) men disproportionately experience kidney failure, representing 16.6% of all cases in 2018-more than double their percentage in the general population. This significant health disparity arises from socioeconomic factors, access issues, and higher disease prevalence.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference.

Introduction: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

Introduction: Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023.

Exploring the Therapeutic Potential of Benfotiamine in a Sporadic Alzheimer's-Like Disease Rat Model: Insights into Insulin Signaling and Cognitive function.

Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents.

Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.

Novel pathways of vitamin D3, lumisterol 3 (L3), and tachysterol 3 (T3) activation have been discovered, initiated by CYP11A1 and/or CYP27A1 in the case of L3 and T3. The resulting hydroxymetabolites enhance protection of skin against DNA damage and oxidative stress; stimulate keratinocyte differentiation; exert anti-inflammatory, antifibrogenic, and anticancer activities; and inhibit cell proliferation in a structure-dependent manner. They act on nuclear receptors, including vitamin D receptor, aryl hydrocarbon receptor, LXRα/β, RAR-related orphan receptor α/γ, and peroxisome proliferator-activated receptor-γ, with selectivity defined by their core structure and distribution of hydroxyl groups.

Myofiber-specific lipidomics unveil differential contributions to insulin sensitivity in individuals of African and European ancestry.

Aims: Individuals of African ancestry (AA) present with lower insulin sensitivity compared to their European counterparts (EA). Studies show ethnic differences in skeletal muscle fiber type (lower type I fibers in AA), muscle fat oxidation capacity (lower in AA), whilst no differences in total skeletal muscle lipids. However, skeletal muscle lipid subtypes have not been examined in this context.

Cervical cancer prevention and care in HIV clinics across sub-Saharan Africa: results of a facility-based survey.

Introduction: To eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub-Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics.

Methods: Our facility-based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

A quantitative study to assess cardiovascular risks among older African American women living in rural black belt areas of Alabama.

Limited information is available regarding the knowledge of Cardiovascular Disease (CVD) risk factors and the actual risk behaviors among African American (AA) older women living in rural areas of Alabama. A pilot study of needs assessment for CVD prevention behaviors was conducted to collect such data from rural AA women. This paper reports the quantitative part of the needs assessment of this pilot study.

Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.

ROCK Inhibitor Fasudil Attenuates Neuroinflammation and Associated Metabolic Dysregulation in the Tau Transgenic Mouse Model of Alzheimer's Disease.

Background: The pathological manifestations of Alzheimer's disease (AD) include not only brain amyloid β protein (Aβ) containing neuritic plaques and hyperphosphorylated tau (p-- tau) containing neurofibrillary tangles but also microgliosis, astrocytosis, and neurodegeneration mediated by metabolic dysregulation and neuroinflammation.

Methods: While antibody-based therapies targeting Aβ have shown clinical promise, effective therapies targeting metabolism, neuroinflammation, and p-tau are still an urgent need. Based on the observation that Ras homolog (Rho)-associated kinases (ROCK) activities are elevated in AD, ROCK inhibitors have been explored as therapies in AD models.

A novel role for KIFC1-MYH9 interaction in triple-negative breast cancer aggressiveness and racial disparity.

African American (AA) women are twice as likely to develop triple-negative breast cancer (TNBC) as women of European descent. Additionally, AA women with TNBC present a much more aggressive disease course than their European American (EA) counterparts. Thus, there is an unmet clinical need to identify race-specific biomarkers and improve survival outcomes in AA patients with TNBC.

Variant level heritability estimates of type 2 diabetes in African Americans.

Type 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA).