Structure-Function Analysis of CYP105A1 in the Metabolism of Nonsteroidal Anti-inflammatory Drugs.

CYP105A1 exhibits monooxygenase activity to a wide variety of structurally different substrates with regio- and stereospecificity, making its application range broad. Our previous studies have shown that CYP105A1 wild type and its variants metabolize 12 types of nonsteroidal anti-inflammatory drugs (NSAIDs). In particular, the R84A variant exhibited a high activity against many NSAIDs.

Robotic sugarbaker parastomal hernia repair: updated series and outcomes.

Purpose: To present updated outcomes after previously describing a novel technique for the robotic repair of parastomal hernias.

Methods: Patients who underwent parastomal hernia repair with a robotic Sugarbaker technique at a tertiary hernia center were identified from an institutional database. The approach involves mesh placement in the intraperitoneal or preperitoneal position after closure of the fascial defect.

Incidence of Adjacent Synchronous Ipsilateral Infiltrating Carcinoma and/or Ductal Carcinoma In Situ in Patients Diagnosed with Flat Epithelial Atypia by Core Needle Biopsy (TBCRC 034).

Background: Flat epithelial atypia (FEA), a rare breast proliferative lesion, is often diagnosed following core biopsy (CB) of mammographic microcalcifications. In the prospective multi-institution TBCRC 034 trial, we investigate the upgrade rate to ductal carcinoma in situ (DCIS) or invasive cancer following excision for patients diagnosed with FEA on CB.

Patients And Methods: Patients with a breast imaging reporting and data system (BI-RADS) ≤ 4 imaging abnormality and a concordant CB diagnosis of FEA were identified for excision.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Is the cortisol awakening response truly a response to awakening? Replication and extension using overnight sampling.

The cortisol awakening response (CAR) is a discrete component of the circadian cortisol profile. Evidence suggests that the CAR is a deviation from the pre-awakening increase in cortisol concentration, although this has yet to be replicated. Therefore, the purpose of this study was to replicate this finding and to investigate further the extent to which the CAR is distinct from the circadian profile.

Basic Science and Pathogenesis.

Background: In 43-63% of symptomatic Alzheimer's disease (AD) patients, there is an observed accumulation of misfolded alpha-synuclein (αSyn). Two primary αSyn subtypes have been identified based on the underlying spreading pattern of this pathology: caudo-rostral and amygdala-predominant. Interactions between pathological TDP-43, Tau, and αSyn can aggravate their spread and aggregation.

Basic Science and Pathogenesis.

Background: Brain arteriolosclerosis (B-ASC) is a pathologic hallmark characterized by dysmorphic brain arteriolar wall thickening. B-ASC is a common finding at autopsy in aged persons - some degree of B-ASC is seen in >80% of brains beyond age 80 years - and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC.

Basic Science and Pathogenesis.

Background: The recent approval of two anti-amyloid antibodies, Aducanamab and Lecanamab, have set the stage for the next generation of anti-amyloid treatments. Despite the capability of these treatments to lower Aβ brain levels, there is thus far limited clinical efficacy on cognitive outcomes. Because eligibility for treatment includes individuals with MCI or mild dementia, that often harbor mixed pathologies, the cognitive impact of other brain pathologies may be important.

Basic Science and Pathogenesis.

Background: Patients with Alzheimer's Disease (AD) frequently manifest comorbid neuropsychiatric symptoms (NPS) with depression and anxiety being most prevalent. Previously we identified shared genetic risk loci between AD and major depressive disorder (MDD). In another study, we constructed a polygenic risk score (PRS) based on MDD-GWAS data and demonstrated its performance in predicting depression onset in LOAD patients.

Technology Enhanced Multidisciplinary Cancer Conferences in Gynecologic Oncology: Impact on Quality and Education.

Multidisciplinary cancer conferences (MCCs) improve patient outcomes. Our goals were to investigate the impact of a technology platform, navify® Clinical Hub for Tumor Boards (nCH) on the quality and educational value of gynecologic oncology MCCs. We conducted a prospective, mixed methods study of the gynecologic oncology MCC at a comprehensive cancer center from 2020 to 2023.

Basic Science and Pathogenesis.

Background: Prolonged exposure to LED-light has been associated with impaired sleep quality and pathogenesis of various diseases, including Alzheimer's Disease (AD). Red light therapy has been indicated as a non-invasive way of reducing anxiety, mood and sleep optimization in neurodegenerative disorders but its endogenous mechanisms are insufficiently comprehended. Hence, we assessed the effects of scheduled red-light exposure on clock genes-Bmal1 and Per 1 expression, feacal boli frequency, and anxiety-like responses in prolonged LED-light exposed rats.

Complex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.

Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively.

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.

Basic Science and Pathogenesis.

Background: Traumatic brain injury (TBI) is recognized as one major, potentially modifiable risk factor for neurodegenerative disease (NDD). Autopsy studies describe a range of neuropathologies in a proportion of individuals surviving late after TBI, most frequently the tau associated pathology, chronic traumatic encephalopathy neuropathologic change (CTE-NC). In addition to tau, other NDD pathologies are described.

Computational fluid particle dynamics modeling of tangential flow filtration in perfusion cell culture.

Membrane fouling is a common and complex challenge with cell culture perfusion process in biopharmaceutical manufacturing that can have detrimental effects on the process performance. In this study, we evaluated a method to calculate the hollow fiber membrane resistance at different time points for water and supernatant. In addition, the number of subvisible particles of < 200 nm.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is highly comorbid with Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), and the combined AD+LATE-NC is more common than either pathology alone. However, the topographic relationship between tau and TDP-43 in AD+LATE-NC remains unclear.

Method: We analyzed the data from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) participants.

Basic Science and Pathogenesis.

Background: Heparan sulfate (HS) interacts with many important proteins. These interactions are primarily driven by electrostatics, with specificity determined by sulfation patterns. Although 3-O-sulfation is a rare modification in HS, several genome-wide association studies (GWAS) revealed that the Hs3st1 gene, encoding HS-3-O-sulfotransferase-1, is significantly linked to late onset AD risk.

Basic Science and Pathogenesis.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) denotes TDP-43 deposition in older age and is consequential for cognitive function. Currently there is no way to identify LATE-NC during life. Some forms of TDP-43 deposition in younger age, related to frontotemporal dementia (FTD), are associated with pronounced asymmetrical atrophy of the temporal lobe.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) risk and progression are significantly influenced by ApoE genotypes, with ApoE4 increasing and ApoE2 decreasing the susceptibility compared to ApoE3. Understanding metabolic pathways affected by ApoE genotypes will help decipher disease development and identify new therapeutic targets.

Method: This study investigates the impact of ApoE genotypes on aging brain metabolic trajectories using human ApoE-targeted replacement mice.

Basic Science and Pathogenesis.

Background: Peripheral metabolic health status can reflect and/or contribute to the risk of Alzheimer's disease (AD). Peripheral metabolic health status can be indicated by metabolic health markers, such as inflammatory biomarker glycoprotein acetyls (GlycA) and specific components of lipoproteins (e.g.

Basic Science and Pathogenesis.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) has been recently recognized as a cause of dementia in the elderly. LATE and Alzheimer's disease (AD) share similar clinical presentations, and their neuropathological changes-LATE-NC and ADNC-commonly co-occur in the brains of individuals with dementia. Frontotemporal degeneration (FTLD-TDP) represents another group of TDP-43-associated neurodegenerative diseases.

Basic Science and Pathogenesis.

Background: Anti- Aβ monoclonal antibodies are the first FDA-approved treatments for AD that slow cognitive decline and lower Aβ plaques. Our goal is to identify the epitope specificities of antibodies in human blood that are associated with AD and NC and determine the predicted protein targets of these antibodies.

Method: 101 AD (MMSE < 27) and 98 NC (MMSE > 27) serum samples were obtained from the UCI tissue repository.

Basic Science and Pathogenesis.

Background: An important hallmark of Alzheimer's Disease (AD) is the presence of neurofibrillary tangles (NFTs) composed of phosphorylated tau, which are commonly assessed using AT8 immunostains. Identifying additional markers to characterize the spectrum of NFT pathology is crucial for advancing our understanding and diagnosis of AD. This study introduces new potential markers to differentiate between tangles and healthy neurons.

Basic Science and Pathogenesis.

Background: An emerging theory suggests a link between Alzheimer's disease (AD) and microbial infection. Notably, various microbes have been detected in the post-mortem brains of AD patients and murine models. However, there exists a gap in research concerning the presence and role of microbial infection in the AD retina, which shares common pathogenesis with the brain.