Optimizing RNA extraction methods for high-throughput transcriptome sequencing of formalin-fixed paraffin-embedded cardiac tissue specimens.

Archived FFPE cardiac tissue specimens are valuable for molecular studies aimed at identifying biomarkers linked to mortality in cardiovascular disease. Establishing a reliable and reproducible RNA extraction method is critical for generating high-quality transcriptome sequences for molecular assays. Here, the efficiency of four RNA extraction methods: Qiagen AllPrep DNA/RNA method (Method QP); Qiagen AllPrep DNA/RNA method with protocol modification on the ethanol wash step after deparaffinization (Method QE); CELLDATA RNA extraction (Method BP) and CELLDATA RNA extraction with protocol modifications on the lysis step (Method BL) was compared on 23 matching FFPE cardiac tissue specimens (n = 92).

Transcriptome studies of congenital heart diseases: identifying current gaps and therapeutic frontiers.

Congenital heart disease (CHD) are genetically complex and comprise a wide range of structural defects that often predispose to - early heart failure, a common cause of neonatal morbidity and mortality. Transcriptome studies of CHD in human pediatric patients indicated a broad spectrum of diverse molecular signatures across various types of CHD. In order to advance research on congenital heart diseases (CHDs), we conducted a detailed review of transcriptome studies on this topic.

In-Hospital Versus Out-of-Hospital Stroke Onset Comparison of Process Metrics in a Community Primary Stroke Center.

Objective: To examine in-hospital stroke onset metrics and outcomes, quality of care, and mortality compared with out-of-hospital stroke in a single community-based primary stroke center.

Patients And Methods: Medical records of in-hospital stroke onset were compared with out-of-hospital stroke onset alert data between January 1, 2013 and December 31, 2019. Time-sensitive stroke process metric data were collected for each incident stroke alert.

Use of a Shear Reduction Surface for Prehospital Transport: A Randomized Crossover Study.

Objective: To compare the effectiveness of an antishear mattress overlay (ASMO) with a standard ambulance stretcher surface in reducing pressure and shear and increasing patient comfort.

Methods: In this randomized, crossover design, adults in three body mass index categories served as their own controls. Pressure/shear sensors were applied to the sacrum, ischial tuberosity, and heel.

In-Hospital Stroke Care: A Six-Year Community-Based Primary Stroke Center Experience.

Background And Purpose: In-hospital stroke-onset assessment and management present numerous challenges, especially in community hospitals. Comprehensive analysis of key stroke care metrics in community-based primary stroke centers is under-studied.

Methods: Medical records were reviewed for patients admitted to a community hospital for non-cerebrovascular indications and for whom a stroke alert was activated between 2013 and 2019.

Androgen Deprivation Therapy Use and Risk of Mild Cognitive Impairment in Prostate Cancer Patients.

Introduction: We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients.

Methods: We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted.

Limited diagnostic impact of duplications <1 Mb of uncertain clinical significance: a 10-year retrospective analysis of reporting practices at the Mayo Clinic.

Purpose: Copy-number variants (CNVs) of uncertain clinical significance are routinely reported in a clinical setting only when exceeding predetermined reporting thresholds, typically based on CNV size. Given that very few genes are associated with triplosensitive phenotypes, it is not surprising that many interstitial duplications <1 Mb are found to be inherited and anticipated to be of limited or no clinical significance.

Methods: In an effort to further refine our reporting criteria to maximize diagnostic yield while minimizing the return of uncertain variants, we performed a retrospective analysis of all clinical microarray cases reported in a 10-year window.

Associations between cerebrospinal fluid total phosphatidylcholines, neurodegeneration, cognitive decline, and risk of mild cognitive impairment in the Mayo Clinic Study of Aging.

It is unclear whether cerebrospinal fluid (CSF) phosphatidylcholines (PCs) are associated with neuroimaging measures of amyloid deposition and neurodegeneration (glucose metabolism, cortical thickness, and hippocampal volume), cognitive decline, or risk of mild cognitive impairment (MCI) among cognitively unimpaired older adults. This study investigated the associations of 19 individual CSF PC concentrations and their total sum with cross-sectional and longitudinal measures of amyloid deposition and neurodegeneration, global and domain-specific cognitive z-scores, and risk of MCI among 655 cognitively unimpaired participants, mean age of 71 years, enrolled in the Mayo Clinic Study of Aging. Neither the CSF total PC concentration nor individual CSF PCs were cross-sectionally or longitudinally associated with neuroimaging measures, cognition, or risk of MCI.

Prostate Cancer, Use of Androgen Deprivation Therapy, and Cognitive Impairment: A Population-based Study.

Introduction: The association of prostate cancer and androgen deprivation therapy (ADT) use with the odds of developing mild cognitive impairment (MCI) was determined in men from the population-based Mayo Clinic Study of Aging (MCSA).

Methods: The study included 2513 men (mean age of 73.1 y) enrolled in the MCSA.

Longitudinal association between phosphatidylcholines, neuroimaging measures of Alzheimer's disease pathophysiology, and cognition in the Mayo Clinic Study of Aging.

Plasma phosphatidylcholines (PCs) have been examined in the context of Alzheimer's disease dementia. However, their association with longitudinal changes in amyloid deposition remains unknown. This study investigated the associations of 8 plasma PC levels (PC aa [14:0_14:0], PC aa [16:0_16:0], PC aa [16:0_18:2], PC aa [16:0_22:6], PC aa [18:0_18:0], PC aa [18:0_18:1], PC aa [18:0_20:4], PC aa [18:1_18:1]) with cross-sectional and longitudinal measures of amyloid deposition, Alzheimer's disease-associated neurodegeneration (glucose metabolism and cortical thickness), and cognition (global- and domain-specific) of 1440 cognitively unimpaired participants (47% female, aged 50.

Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.

Importance: Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau).

Objective: To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations.

The Cross-sectional and Longitudinal Associations Between IL-6, IL-10, and TNFα and Cognitive Outcomes in the Mayo Clinic Study of Aging.

Background: Chronic inflammation has been linked with geriatric-related conditions, including dementia. Inflammatory cytokine levels, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) α, in the blood have been associated with cognitive impairment and decline. However, evidence has been mixed.

Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging.

Objective: We investigated different dimensions of subjective cognitive decline (SCD) to determine which was the best prognostic risk factor for incident mild cognitive impairment (MCI) among cognitively unimpaired participants.

Methods: We included 1,167 cognitively unimpaired participants, aged 70 to 95 years, from the Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed memory test and the 39-item Everyday Cognition [ECog] scale, which included a validated 12-item derivative) and a single question assessing worry about cognitive decline. We evaluated multiple ways to dichotomize scores.

Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging.

Objective: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics.

Methods: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects.

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

Introduction: We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ.

Methods: Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181.

Results: Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired.

The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging.

Levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, and their ratio in the blood may be useful for monitoring those at risk of cognitive and functional decline. However, the association between IGF measures and functional and cognitive outcomes has been mixed, and the associations may vary by sex. The present study investigated the cross-sectional, sex-specific associations between serum measures total IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio, gait speed, and cognition in 1320 cognitively unimpaired participants aged 50-95 years enrolled in the Mayo Clinic Study of Aging.

Longitudinal Association Between Brain Amyloid-Beta and Gait in the Mayo Clinic Study of Aging.

Background: The longitudinal association between cerebral amyloid-beta (Aβ) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined.

Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aβ, cortical thickness, and gait measurements. Cerebral Aβ deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor).

Plasma Sphingolipids are Associated With Gait Parameters in the Mayo Clinic Study of Aging.

Background: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men.

Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging.

Importance: The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood.

Objectives: To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months.

Design, Setting, And Participants: The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013.

Longitudinal association between diabetes and cognitive decline: The National Health and Aging Trends Study.

Type II diabetes mellitus (DM) is associated with increased risk of dementia; however, few studies have examined the longitudinal association between DM and cognitive outcomes in large nationally representative cohorts. We investigated these associations in 7605 participants enrolled in the National Health and Aging Trends Study, a nationally representative prospective study of Medicare beneficiaries ≥65, from 2011 to 2015. Participants or proxy respondents reported DM and dementia diagnosis, and participants completed immediate and delayed recall word list learning tests and the Clock Drawing Test.

The impact of postpartum hemorrhage on hospital length of stay and inpatient mortality: a National Inpatient Sample-based analysis.

Background: Postpartum hemorrhage is a major cause of maternal morbidity and mortality, but the association between postpartum hemorrhage and hospital length of stay has not been rigorously investigated.

Objective: We explored the impact of postpartum hemorrhage on hospital length of stay and inpatient mortality, as these outcomes have both clinical and economic significance.

Study Design: We performed a retrospective analysis using data from the National Inpatient Sample database during the 2012 through 2013 time period.

Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging.

Objectives: To determine the cross-sectional association between cerebral amyloid-beta (Aβ) deposition and gait.

Design: Cross-sectional.

Setting: Population-based cohort study in Olmsted County, MN.

Comparison of Gait Parameters for Predicting Cognitive Decline: The Mayo Clinic Study of Aging.

Background: Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear.

Objective: To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample.