Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which numerous mouse models have been generated. In both AD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of beta-amyloid (Abeta)-containing plaques and neurodegeneration. Characterization of the timing and nature of preplaque dysfunction is important for understanding the progression of this disease and to identify pathways and molecular targets for therapeutic intervention. Hence, we have examined the progression of dysfunction at the morphological, functional, and behavioral levels in the Tg2576 mouse model of AD. Our data show that decreased dendritic spine density, impaired long-term potentiation (LTP), and behavioral deficits occurred months before plaque deposition, which was first detectable at 18 months of age. We detected a decrease in spine density in the outer molecular layer of the dentate gyrus (DG) beginning as early as 4 months of age. Furthermore, by 5 months, there was a decline in LTP in the DG after perforant path stimulation and impairment in contextual fear conditioning. Moreover, an increase in the Abeta42/Abeta40 ratio was first observed at these early ages. However, total amyloid levels did not significantly increase until approximately 18 months of age, at which time significant increases in reactive astrocytes and microglia could be observed. Overall, these data show that the perforant path input from the entorhinal cortex to the DG is compromised both structurally and functionally, and this pathology is manifested in memory defects long before significant plaque deposition.
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http://dx.doi.org/10.1073/pnas.0600948103 | DOI Listing |
Gynecol Oncol
January 2025
Departments of Internal Medicine and Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America; Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States of America.
Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.
Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).
AIDS
January 2025
Botswana Harvard Health Partnership, Gaborone, Botswana.
Objective: To examine the impact of in utero exposure to dolutegravir (DTG)- or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental (ND) outcomes.
Design: Prospective cohort design, enrolling 3 cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based 3-drug ART during pregnancy, and children born to mothers without HIV (CHUU).
Methods: Primary child ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders.
AIDS
January 2025
Internal Medicine Department, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitario de Granada (IBS-Granada), Spain.
Background: Objectives were to determine the prevalence/incidence of HPV-related dysplasia and clearance/acquisition rates of high-risk HPV (HR-HPV) genotypes in genital mucosa of women-LHIV and oropharyngeal and anal mucosa of PLHIV and to evaluate factors related to HR-HPV infection in oropharyngeal mucosa at 12-months.
Material And Methods: Prospective, longitudinal study with 12-month follow-up, enrolled PLHIV between December 2022 and April 2023. At baseline and 12-months, HIV-related clinical and analytical variables were recorded, oropharyngeal mucosa exudates were taken for polymerase chain reaction (PCR) studies for HPV and other sexually transmitted infections, while anal and female genital samples were self-sampled for HPV detection and genotyping by PCR and thin-layer cytology.
Health Serv Res
January 2025
Department of Health Policy, Management and Behavior School of Public Health, University at Albany, State University of New York, Rensselaer, New York, USA.
Objective: To examine the association of Massachusetts Medicaid Accountable Care Organization (ACO) implementation with changes in mental health care utilization in the postpartum period.
Study Setting And Design: We examine care for people with a birth covered by Medicaid or private insurance. We used a difference-in-differences design to compare differences before and after Medicaid ACO implementation for those with Medicaid versus those with private insurance.
Discrimination (unfair treatment due to group membership) is relatively common among adolescents and has been linked to poor sleep and physical health. Individual differences in physiological functioning may moderate these associations. A sample of 323 youth (48% boys, 52% girls; 58.
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