Fluid Intelligence Predicts Change in Depressive Symptoms in Later Life: The Lothian Birth Cohort 1936.

We examined reciprocal, time-ordered associations between age-related changes in fluid intelligence and depressive symptoms. Participants were 1,091 community-dwelling older adults from the Lothian Birth Cohort 1936 study who were assessed repeatedly at 3-year intervals between the ages of 70 and 79 years. On average, fluid intelligence and depressive symptoms worsened with age.

Role of cognitive ability in the association between functional health literacy and mortality in the Lothian Birth Cohort 1936: a prospective cohort study.

Objectives: We investigated the role that childhood and old age cognitive ability play in the association between functional health literacy and mortality.

Design: Prospective cohort study.

Setting: This study used data from the Lothian Birth Cohort 1936 (LBC1936) study, which recruited participants living in the Lothian region of Scotland when aged 70 years, most of whom had completed an intelligence test at age 11 years.

Physical fitness and dementia risk in the very old: a study of the Lothian Birth Cohort 1921.

Background: Previous studies have demonstrated that individual measures of fitness - such as reduced pulmonary function, slow walking speed and weak handgrip - are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old.

Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.

Geometric constraints during epithelial jamming.

As an injury heals, an embryo develops, or a carcinoma spreads, epithelial cells systematically change their shape. In each of these processes cell shape is studied extensively whereas variability of shape from cell-to-cell is regarded most often as biological noise. But where do cell shape and its variability come from? Here we report that cell shape and shape variability are mutually constrained through a relationship that is purely geometrical.

Extragastrointestinal stromal tumors of the pelvic cavity and the vagina: Two case reports and review of the literature.

Gastrointestinal stromal tumors (GISTs) are rare tumors of gastrointestinal (GI) tract with mesenchymal cell origin. Extragastrointestinal stromal tumors (EGISTs) are unusual tumors that exhibit the same immunohistochemical and genetic abnormalities as GISTs and most commonly affect the omentum and mesentery. EGISTs of the pelvis and the female reproductive system are exceedingly rare and a frequent diagnostic pitfall.

DNA methylation and the epigenetic clock in relation to physical frailty in older people: the Lothian Birth Cohort 1936.

Background: The biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals.

Methods: Participants were 791 people aged 70 years from the Lothian Birth Cohort 1936.

Trends in Dental Implant Use in the U.S., 1999-2016, and Projections to 2026.

Dental implants have become an increasingly popular treatment choice for replacing missing teeth. Yet, little is known about the prevalence and sociodemographic distribution of dental implant use in the United States. To address this knowledge gap, we analyzed data from 7 National Health and Nutrition Examination Surveys from 1999 to 2016.

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure.

Delineating the role of cooperativity in the design of potent PROTACs for BTK.

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets.

DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.

Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.

Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures.

Purpose Of Review: To summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF).

Recent Findings: The absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis.

Longitudinal serum S100β and brain aging in the Lothian Birth Cohort 1936.

Elevated serum and cerebrospinal fluid concentrations of S100β, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100β concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100β and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions.

Cognitive function in early and later life is associated with blood glucose in older individuals: analysis of the Lothian Birth Cohort of 1936.

Aims/hypothesis: The aim of this study was to examine whether cognitive function in early and later life, and decline in cognitive function from age 70 to 79 years, are associated with high blood glucose, as measured by HbA, at baseline (age 70), and changes in blood glucose from age 70 to 79.

Methods: Participants (n = 1091) in the Lothian Birth Cohort of 1936 were examined. Fourteen tests were used to assess cognitive functions, grouped into four domains: visuospatial ability, processing speed, memory and crystallised ability.

Oral microbiota in youth with perinatally acquired HIV infection.

Background: Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth.

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure.

Effect of pump type on outcomes in neonates with congenital diaphragmatic hernia requiring ECMO.

Purpose: With the exception of neonatal respiratory failure, most centers are now using centrifugal over roller-type pumps for the delivery of extracorporeal membrane oxygenation (ECMO). Evidence supporting the use of centrifugal pumps specifically in infants with congenital diaphragmatic hernia (CDH) remains lacking. We hypothesized that the use of centrifugal pumps in infants with CDH would not affect mortality or rates of severe neurologic injury (SNI).

Pediatric superior vena cava syndrome: An evidence-based systematic review of the literature.

Superior vena cava syndrome (SVCS) results in vascular, respiratory, and neurologic compromise. A systematic search was conducted to determine the prevalence of pediatric SVCS subtypes and identify clinical characteristics/treatment strategies that may influence overall outcomes. Data from 101 case reports/case series (142 patients) were analyzed.

GWAS on family history of Alzheimer's disease.

Alzheimer's disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer's dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal.