Nexilin in cardiomyopathy: unveiling its diverse roles with special focus on endocardial fibroelastosis.

Cardiac disorders exhibit considerable heterogeneity, and understanding their genetic foundations is crucial for their diagnosis and treatment. Recent genetic analyses involving a growing number of participants have uncovered novel mutations within both coding and non-coding regions of DNA, contributing to the onset of cardiac conditions. The NEXN gene, encoding the Nexilin protein, an actin filament-binding protein, is integral to normal cardiac function.

Identification of a functional missense variant in the matrix metallopeptidase 10 (MMP10) gene in two families with premature myocardial infarction.

A positive family history is a major independent risk factor for atherosclerosis, and genetic variation is an important aspect of cardiovascular disease research. We identified a heterozygous missense variant p.L245P in the MMP10 gene in two families with premature myocardial infarction using whole-exome sequencing.

H-ABC- and dystonia-causing mutations show distinct pathogenic effects.

Mutations in the brain-specific β-tubulin 4A (TUBB4A) gene cause a broad spectrum of diseases, ranging from dystonia (DYT-TUBB4A) to hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Currently, the mechanisms of how variants lead to this pleiotropic manifestation remain elusive. Here, we investigated whether mutations causing either DYT-TUBB4A (p.

Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.

Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls).

Stimulators of the soluble guanylyl cyclase: promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants.

Stimulators of the soluble guanylyl cyclase (sGC) are emerging therapeutic agents in cardiovascular diseases. Genetic alterations of the GUCY1A3 gene, which encodes the α1 subunit of the sGC, are associated with coronary artery disease. Studies investigating sGC stimulators in subjects with CAD and carrying risk-related variants in sGC are, however, lacking.

Classification of ADAMTS binding sites: The first step toward selective ADAMTS7 inhibitors.

Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease. In carotid arteries of rats, neointima formation after balloon-mediated injury goes along with enhanced Adamts7 expression. Vice versa, Adamts7-deficient mice display reduced neointima formation following vascular injury.

Screening of synthetic and natural product databases: Identification of novel androgens and antiandrogens.

The androgen receptor is an important pharmaceutical target for a variety of diseases. This paper presents an in silico/in vitro screening procedure to identify new androgen receptor ligands. The two-step virtual screening procedure uses a three-dimensional pharmacophore model and a docking/scoring routine.

Urinary incontinence management costs are reduced following Burch or sling surgery for stress incontinence.

Objective: The objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence (UI) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a randomized trial comparing these procedures.

Study Design: Resources used for UI management (supplies, laundry, dry cleaning) were self-reported by 491 women at baseline and 24 months after surgery, and total out-of-pocket costs for UI management (in 2012 US dollars) were estimated. Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months.

Accessing and evaluating urologic health information: differences by race/ethnicity and gender.

Patients with urologic symptoms seek information from a variety of sources outside the traditional health care arena. There are differences between the genders and racial/ethnic groups related to sources consulted and confidence in those sources.

A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression.

Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are allelic disorders of the gene CACNA1A encoding the P/Q subunit of a voltage gated calcium channel. While SCA6 is related to repeat expansions affecting the C-terminal part of the protein, EA2 and FHM phenotypes are usually associated with nonsense and missense mutations leading to impaired channel properties. In three unrelated families with dominant cerebellar ataxia, symptoms cosegregated with CACNA1A missense mutations of evolutionary highly conserved amino acids (exchanges p.

Treatment status and risk factors for incidence and persistence of urinary incontinence in women.

Introduction And Hypothesis: The objective of this analysis was to describe urinary incontinence (UI) incidence and persistence over 5 years in association with treatment status, sociodemographic, medical, and lifestyle factors, in a racially/ethnically diverse population-based female sample.

Methods: The Boston Area Community Health Survey enrolled 3,201 women aged 30-79 years of black, Hispanic, and white race/ethnicity. Five-year follow-up was completed by 2,534 women (conditional response rate 83.

Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults.

Objectives: To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years.

Design: Ten-year follow-up of a randomized, controlled single-blind trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no-contact control group.

Setting: Six U.

Relationship of demographic and health factors to cognition in older adults in the ACTIVE study.

Objective: Examine the relationship of demographics and health conditions, alone and in combination, on objective measures of cognitive function in a large sample of community-dwelling older adults.

Method: Baseline data from 2,782 participants in the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study were used to examine relationships of demographics and health conditions with composite scores of memory, reasoning, and speed of processing.

Results: Younger age, increased education, and White race were independently associated with better performance in each cognitive domain after adjusting for gender and health conditions.

The minimum important difference for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form in women with stress urinary incontinence.

Introduction: Minimum important difference (MID) estimates the minimum degree of change in an instrument's score that correlates with a patient's subjective sense of improvement. We aimed to determine the MID for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) using both anchor based and distribution based methods derived using data from the Trial of Midurethral Slings (TOMUS).

Materials And Methods: Instruments for the anchor-based analyses included the urogenital distress inventory (UDI), incontinence impact questionnaire (IIQ), patient global impression of improvement (PGI-I), incontinence episodes (IE) on 7-day bladder diary, and satisfaction with surgical results.

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history.

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD.

The ACTIVE cognitive training interventions and trajectories of performance among older adults.

Objectives: Salthouse illustrated that among Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) participants, cognitive change accelerated following training. Our goal was to determine if this finding persists net of practice, training, and loss of training gains effects.

Methods: We evaluated change over 5 years following cognitive training among older adults (N = 1,659, age 65 to 94).

Condition-specific quality of life 24 months after retropubic and transobturator sling surgery for stress urinary incontinence.

Aims: To compare quality of life (QoL) and factors associated with QoL change after retropubic (RMUS) and transobturator midurethral slings (TMUS) using the Incontinence Impact Questionnaire (IIQ) and the International Consultation on Incontinence Questionnaire (ICIQ).

Methods: Five hundred ninety-seven women in a multicenter randomized trial of RMUS versus TMUS were examined. The IIQ and the ICIQ were obtained at baseline and at 12 and 24 months.

Complementary and alternative therapies for urinary symptoms: use in a diverse population sample qualitative study.

Study participants reported a range of remedies used to treat urinary symptoms, from popular products, such as saw palmetto, to less commonly known remedies, such as moabi. Participants learned about remedies through social network rather than from their primary care provider.

Spiritual well-being in patients with advanced heart and lung disease.

Objective: The purpose of this study was to evaluate levels of spiritual well-being over time in populations with advanced congestive heart failure (CHF) or chronic obstructive lung disease (COPD).

Method: In a prospective, longitudinal study, patients with CHF or COPD (each n = 103) were interviewed at baseline and every 3 months for up to 30 months. At each interview, patients completed: the basic faith subscale of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) questionnaire, the Memorial Symptom Assessment Scale (MSAS), the Rand Mental Health Inventory (MHI), the Multidimensional Index of Life Quality (MILQ), the Sickness Impact Profile (SIP), and the Short Portable Mental Health Questionnaire (SPMSQ).