Circulating Procollagen Type III N-Terminal Peptide and Physical Function in Adults from the Long Life Family Study.

Background: Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was associated with baseline and 7-year change in physical function.

Method: Participants (n = 400) were from the Long Life Family Study, a study of exceptional familial longevity.

Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk.

Background: Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome.

Aims: To evaluate the effect of aspirin on the gut microbiome in a double-blinded, randomised placebo-controlled pilot trial.

Methods: Healthy volunteers aged 50-75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks.

Hmong participants' reactions to return of individual and community pharmacogenetic research results: "A positive light for our community".

Pharmacogenetic research has historically lacked racial and ethnic diversity, limiting the application of findings to minority populations. Recent studies, including the Hmong, have gauged communities' interest in participating in genomic research and receiving their individual results. This study was conducted to create a culturally and linguistically appropriate format to return pharmacogenomic results and identify Minnesota Hmong research participants' reactions to their personal and collective results.

Dietary Polyphenols in Cancer Chemoprevention: Implications in Pancreatic Cancer.

Naturally occurring dietary agents present in a wide variety of plant products, are rich sources of phytochemicals possessing medicinal properties, and thus, have been used in folk medicine for ages to treat various ailments. The beneficial effects of such dietary components are frequently attributed to their anti-inflammatory and antioxidant properties, particularly in regards to their antineoplastic activities. As many tumor types exhibit greater oxidative stress levels that are implicated in favoring autonomous cell growth activation, most chemotherapeutic agents can also enhance tumoral oxidative stress levels in part via generating reactive oxygen species (ROS).

Whole-body MRI in the diagnosis of paediatric CNO/CRMO.

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory disorder affecting the skeleton of children and adolescents. Whole-body MRI (WBMRI) is key in the diagnosis and follow-up of CRMO. Imaging protocols should include sagittal short Tau inversion recovery of the spine, imaging of the hands and feet, and T1 images for distinguishing normal bone marrow.

TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors.

Testosterone regulates dimorphic sexual behaviors in all vertebrates. However, the molecular mechanism underlying these behaviors remains unclear. Here, we report that a newly identified rapid testosterone signaling receptor, Transient Receptor Potential Melastatin 8 (TRPM8), regulates dimorphic sexual and social behaviors in mice.

Antidiabetes constituents, cycloartenol and 24-methylenecycloartanol, from Ficus krishnae.

Ficus krishnae stem bark and leaves are used for diabetes treatment in traditional medicines. Stem bark of F. krishnae was sequentially extracted with hexane, methanol and water, and these extracts were tested for their antihyperglyceamic activity by oral glucose tolerance test (OGTT) in overnight fasted glucose loaded normal rats.

Age-associated decline in neural, endocrine, and immune responses in men and women: Involvement of intracellular signaling pathways.

The aim of this study was to investigate the alterations in the neuroendocrine-immune functions by using human peripheral blood mononuclear cells (hPBMCs) from three age groups (young, middle-aged, and old) of men and women for the analyses of lymphocyte proliferation and cytokine production, expression of cell signaling molecules, nitric oxide (NO) production, and expression of p-tyrosine hydroxylase (TH). Serum was examined for levels of testosterone in men, 17-β-estradiol in women, and cortisol in both sexes. Lymphoproliferation, expression of p-ERK, p-CREB, p-Akt, and p-TH, and levels of serum sex steroid hormones declined with age in men and women.

Revision total elbow arthroplasty: Is it safe to perform a single-stage revision for presumed aseptic loosening based on clinical assessment, normal inflammatory markers, and a negative aspiration?

Background: Revision total elbow arthroplasty (TEA) is a challenging procedure that is becoming increasingly common. In our unit, we regard it as essential to exclude infection as the underlying cause of TEA loosening. In all patients with arthroplasty loosening, we undertake a careful history and examination, perform radiographs, monitor inflammatory markers, and undertake a joint aspiration.

De novo transcriptome analysis unravels tissue-specific expression of candidate genes involved in major secondary metabolite biosynthetic pathways of implication for pharmacological potential.

Key Message: The present study provides comparative transcriptome analysis, besides identifying functional secondary metabolite genes of with pharmacological potential for future functional genomics, and metabolomic engineering of secondary metabolites from this plant towards diversified biomedical applications.

Abstract: is a widely used medicinal plant of the traditional Indian system of medicine with wide pharmacological potential to treat several disorders. The present study aimed to carry out comparative transcriptome analysis in leaf and root tissue of using Illumina paired end sequencing to identify tissue-specific functional genes involved in the biosynthesis of secondary metabolites, contributing to its therapeutic efficacy.

Lung Function and Gene Expression of Pathogen Recognition Pathway Receptors: the Cardia Lung Study.

Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV), Forced Vital Capacity (FVC) and FEV/FVC). We studied gene expression levels and lung function in the Coronary Artery Risk Development in Young Adults study.

Patterns of multi-domain cognitive aging in participants of the Long Life Family Study.

Maintaining good cognitive function at older age is important, but our knowledge of patterns and predictors of cognitive aging is still limited. We used Bayesian model-based clustering to group 5064 participants of the Long Life Family Study (ages 49-110 years) into clusters characterized by distinct trajectories of cognitive change in the domains of episodic memory, attention, processing speed, and verbal fluency. For each domain, we identified 4 or 5 large clusters with representative patterns of change ranging from rapid decline to exceptionally slow change.

Sepsis and Septic Shock - Basics of diagnosis, pathophysiology and clinical decision making.

Sepsis and septic shock are major causes of mortality among hospitalized patients. The sepsis state is due to dysregulated host response to infection, leading to inflammatory damage to nearly every organ system. Early recognition of sepsis and appropriate treatment with antibiotics, fluids, and vasopressors is essential to reducing organ system injury and mortality.

Validation of a hybrid approach to standardize immunophenotyping analysis in large population studies: The Health and Retirement Study.

Traditional manual gating strategies are often time-intensive, place a high burden on the analyzer, and are susceptible to bias between analyzers. Several automated gating methods have shown to exceed performance of manual gating for a limited number of cell subsets. However, many of the automated algorithms still require significant manual interventions or have yet to demonstrate their utility in large datasets.

Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Background: Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.

Objectives: We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.

Methods: We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 y who were free of diabetes and other major chronic diseases at baseline (2008-2011).

Hepatic and Skeletal Muscle Adiposity Are Associated with Diabetes Independent of Visceral Adiposity in Nonobese African-Caribbean Men.

Adipose tissue (AT) around and within non-AT organs (i.e., ectopic adiposity) is emerging as a strong risk factor for type 2 diabetes (T2D).

Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants.

Objective: Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.

Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events.

Objectives: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents.

Microtubule dynamics in healthy and injured neurons.

Most neurons must last a lifetime and their microtubule cytoskeleton is an important contributor to their longevity. Neurons have some of the most stable microtubules of all cells, but the tip of every microtubule remains dynamic and, although requiring constant GTP consumption, microtubules are always being rebuilt. While some ongoing level of rebuilding always occurs, overall microtubule stability can be modulated in response to injury and stress as well as the normal developmental process of pruning.

Prevalence of clinically actionable disease variants in exceptionally long-lived families.

Background: Phenotypic expression of pathogenic variants in individuals with no family history of inherited disorders remains unclear.

Methods: We evaluated the prevalence of pathogenic variants in 25 genes associated with Mendelian-inherited disorders in 3015 participants from 485 families in the Long Life Family Study (LLFS). Boot-strapping and Fisher's exact test were used to determine whether allele frequencies in LLFS were significantly different from the allele frequencies reported in publicly available genomic databases.

Genetics of physiological dysregulation: findings from the long life family study using joint models.

Recently, Mahalanobis distance (D) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed D variants using sets of biomarkers collected at the two visits of the Long Life Family Study (LLFS) and performed joint analyses of longitudinal observations of D and follow-up mortality in LLFS using joint models. We found that D is significantly associated with mortality (hazard ratio per standard deviation: 1.

Urinary Arsenic Species are Detectable in Urban Underserved Hispanic/Latino Populations: A Pilot Study from the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS).

Background: Hispanics/Latinos represent >15% of the United States (US) population and experience a high burden of cardiovascular disease (CVD) and diabetes. Dietary exposure, particularly to arsenic (As), may be associated with CVD and diabetes in Hispanics/Latinos. Rural populations in the US exposed to As in drinking water have increased risk of diabetes and CVD; however, little is known about the risk among urban populations with low As in water who are mostly exposed to As through food.

Cytomegalovirus and cancer-related mortality in the national health and nutritional examination survey.

Purpose: Cytomegalovirus (HCMV) is a common viral infection that shapes lifelong immunity. A history of infection with HCMV has been associated with many chronic diseases, including cancer. In addition, prospective cohort studies have established that HCMV is associated with all-cause mortality.

Composite Measure of Physiological Dysregulation as a Predictor of Mortality: The Long Life Family Study.

Biological aging results in changes in an organism that accumulate over age in a complex fashion across different regulatory systems, and their cumulative effect manifests in increased physiological dysregulation (PD) and declining robustness and resilience that increase risks of health disorders and death. Several composite measures involving multiple biomarkers that capture complex effects of aging have been proposed. We applied one such approach, the Mahalanobis distance (D), to baseline measurements of various biomarkers (inflammation, hematological, diabetes-associated, lipids, endocrine, renal) in 3,279 participants from the Long Life Family Study (LLFS) with complete biomarker data.