Introduction: Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.
Methods: The WADRC sample included 930 participants.
Introduction: This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression.
Methods: In a sample of = 201 participants (63.81 ± 6.
Iron accumulation and mitochondrial dysfunction in astroglia are reported in Parkinson's disease (PD). Astroglia control iron availability in neurons in which dopamine (DA) synthesis is affected in PD. Despite their intimate relationship the role of DA in astroglial iron homeostasis is limited.
View Article and Find Full Text PDFIntroduction: Pressure injuries (PIs) continue to remain one of the most common and debilitating complications seen adding to the financial burden of the patients and caregivers. The available VAC (vacuum assisted closure) systems are expensive. In our case series we have applied low-cost negative pressure dressing (NPD) for sacral pressure injuries in five patients along with individualised rehabilitation protocol which resulted in accelerated healing of their PIs and improved functional outcome.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.
View Article and Find Full Text PDFChikungunya virus (CHIKV) is a mosquito-transmitted alphavirus causing fever, myalgia, and debilitating joint swelling and pain, which in many patients becomes chronic. The frequent epidemics of CHIKV across the world pose a significant public health burden necessitating the development of effective antiviral therapeutics. A cellular imaging-based high-content screening of natural compounds identified withaferin A (WFA), a steroidal lactone isolated from the plant Withania somnifera, as a potent antiviral against CHIKV.
View Article and Find Full Text PDFIntroduction: Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).
Methods: We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).
Results: WGMS identified 9756 differentially methylated positions (DMPs) in persons with MCI, including 1743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport.
Initiation of protein translation is one of the key steps in protein synthesis carried out by translation initiation factors in conjunction with ribosomes. The roles and mechanisms of these initiation factors in prokaryotic and eukaryotic protein synthesis are well understood. However, they are only beginning to be understood in trypanosomatids.
View Article and Find Full Text PDFIntroduction: Osteoporosis is a common yet underdiagnosed condition that increases fracture risk and disability. It is particularly prevalent in individuals with musculoskeletal and neurological disorders due to factors like immobility and disuse. Despite its impact, awareness of osteoporosis remains low, especially in this high-risk population.
View Article and Find Full Text PDFAgonists enhance receptor activity by providing net-favorable binding energy to active over resting conformations, with efficiency (η) linking binding energy to gating. Previously, we showed that in nicotinic receptors, η-values are grouped into five structural pairs, correlating efficacy and affinity within each class, uniting binding with allosteric activation (Indurthi and Auerbach, 2023). Here, we use molecular dynamics (MD) simulations to investigate the low-to-high affinity transition (L→H) at the Torpedo α-δ nicotinic acetylcholine receptor neurotransmitter site.
View Article and Find Full Text PDFObjective: To characterize neighborhood-level area deprivation's association with oropharyngeal carcinoma clinicodemographics, tumor staging, recurrence, and overall survival.
Study Design: Retrospective study.
Setting: Single institution academic medical center.
Introduction: Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.
Methods: Cross-sectional plasma samples (n=252) were analyzed using Alamar's NULISAseq CNS panel.
Effective antiviral drugs are essential to combat COVID-19 and future pandemics. Although many compounds show antiviral activity, only a few retain effectiveness against SARS-CoV-2. Here, we show that berbamine (Berb) is effective against SARS-CoV, MER-CoV, SARS-CoV-2 and its variants, including the XBB.
View Article and Find Full Text PDFIntroduction: Late-life air pollution exposure is associated with an increased risk for dementia, with this effect exacerbated among apolipoprotein E-4 (ApoE-4) carriers. However, whether midlife occupational exposures likewise influence dementia outcomes, and varies as a function of ApoE-4 status is unknown.
Methods: Using data from 3814 participants in the Wisconsin Longitudinal Study (WLS), we employed weighted logistic regression to evaluate associations between midlife occupational respiratory exposures and late-life air pollution on all-cause dementia risk, stratified by ApoE-4 status.
COX-2 and 5-LOX are major enzymes implicated in inflammatory processes and have a crucial role in the pathogenesis of inflammatory disorders and malignancies. Designing antagonists that may concurrently interact with several receptors is a viable technique; thus, blocking these two targets with a single chemical compound might provide an efficient therapeutic approach. In-silico approaches have been employed to find polypharmacological inhibitors, especially for drug repurposing and multitarget drug design.
View Article and Find Full Text PDFDiploid mammalian genome has paired alleles for each gene; typically allowing for equal expression of the two alleles within the cell/tissue. However, genetic regulatory elements and epigenetic modifications can disrupt this equality, leading to preferential expression of one allele. Examining high-confidence allele-specific expression (ASE) is vital for understanding genetic variations and their impact on major diseases like cancers and diabetes.
View Article and Find Full Text PDFIntroduction: Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.
Methods: Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+), neocortex-only (T+), or both (T+). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.
Background: Klotho, encoded by the gene, is an anti-aging and neuroprotective protein. KL-VS heterozygosity (KL-VS) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau).
Objective: We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk.
Hypospadias (HS) is a congenital defect that occurs due to defective androgenization. It is characterized by the aberrant location of the urinary meatus on the ventral aspect of the penis with various degrees of severity. The molecular mechanisms and genetic associations underlying the condition remain largely unknown.
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