Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of Founder Variants.

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM.

Terminal osseous dysplasia with pigmentary defects and cardiomyopathy caused by a novel FLNA variant.

Terminal osseous dysplasia with pigmentary defects (TODPD), also known as digitocutaneous dysplasia, is one of the X-linked filaminopathies caused by a variety of FLNA-variants. TODPD is characterized by skeletal defects, skin fibromata and dysmorphic facial features. So far, only a single recurrent variant (c.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

Background: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms.

Methods: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon.

ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion.

Atlas of the clinical genetics of human dilated cardiomyopathy.

Aim: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort.

A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance.

Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the significance of GLA gene variants and to calculate the prevalence of definite classical and uncertain cases.

Improving quality of care for patients with chronic obstructive pulmonary disease.

A chronic obstructive pulmonary disease (COPD) project was initiated at 18 primary care clinical practices located in rural areas of northeastern Maine to improve the diagnosis and treatment of patients with COPD through the adoption of evidence-based and best practice clinical guidelines for care management. Clinical guidelines based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were implemented by the practices using the Institute for Healthcare Improvement Breakthrough Series learning session model. Practice barriers and patient barriers were identified through focus groups and were then addressed at the learning sessions and through direct contact with the practices.

Workplace exacerbation of asthma symptoms: findings from a population-based study in Maine.

In this population-based study of asthma in the State of Maine, the authors investigated how often asthma symptoms were exacerbated in the workplace. Participants from 5 hospital service areas in Maine completed a telephone questionnaire. Of 474 adult participants (18-65 yr of age) employed during the preceding year and for whom information on occupation and industry was available, 64 (13.

Increased cardiac workload by closure of the ductus arteriosus leads to hypertrophy and apoptosis rather than to hyperplasia in the late fetal period.

It is generally thought that adult mammalian cardiomyocytes compensate for an increased workload by hypertrophy, whereas fetal myocardium grows by cellular proliferation. We analyzed the response of late-fetal rat hearts upon an increased workload imposed by premature constriction of the ductus arteriosus with indomethacin. Initially the fetal heart responds by proliferative growth, as both wet weight and labeling index (bromodeoxyuridine incorporation) of the ventricles increased, whereas neither a change in the fibroblast fraction, ploidy and nucleation in the ventricles is observed.

Physician specialty practices. Strategic survival for rural hospitals.

Rural hospital financial performance can be boosted by implementing a model for providing greater access to specialty care. Each of these models has its own unique financial implications and advantages for rural hospitals.

Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data.

Quantification of mRNAs using real-time polymerase chain reaction (PCR) by monitoring the product formation with the fluorescent dye SYBR Green I is being extensively used in neurosciences, developmental biology, and medical diagnostics. Most PCR data analysis procedures assume that the PCR efficiency for the amplicon of interest is constant or even, in the case of the comparative C(t) method, equal to 2. The latter method already leads to a 4-fold error when the PCR efficiencies vary over just a 0.

Development of a prototype system for statewide asthma surveillance.

Objectives: We developed and evaluated a statewide and community-level asthma surveillance system.

Methods: Databases and measures included a community prevalence survey, hospital admissions data, emergency department/outpatient clinic visit records, and a physician survey of diagnosis and treatment practices. We evaluated the system in 5 Maine communities varying in population and income.

Non-radioactive in situ detection of mRNA in ES cell-derived cardiomyocytes and in the developing heart.

Non-radioactive in situ hybridisation is an excellent method to visualise mRNA molecules within their topographical context. Recently we have reported a new non-radioactive in situ hybridisation procedure on tissue sections that is essentially based on the whole mount in situ hybridisation procedure. This method is superior in spatial resolution and sensitivity compared to the radioactive in situ hybridisation procedure.

Developmental changes in rat cardiac DNA, RNA and protein tissue base: implications for the interpretation of changes in gene expression.

During cardiac development the expression levels of many genes change as determined by Northern blot, dot blot, RNase protection, quantitative RT-PCR. Western blot or immunoprecipitation analyses. It is not always realized that the total amount of RNA or protein per gram of heart, dubbed tissue base, may change significantly during development as well.

Access to physicians, obstetric care use, and adequacy of prenatal care for Medicaid patients in Maine: 1985-1989.

Objective: To document trends in prenatal care utilization and provider participation in the Maine Medicaid program for the period 1985-1989, and to examine the effect of physician availability on adequacy of care.

Methods: Five years of Medicaid claims data and 3 years of claims data linked to birth certificates were analyzed.

Results: Large decreases in overall physician participation in the Medicaid program were due to reductions in the number of family physicians and general practitioners, whereas the number of obstetricians increased during this time.

Characterization of four novel CAG repeat-containing cDNAs.

Stretches of CAG nucleotides coding for the amino acid glutamine are an important feature of many transcription factors and genes that are involved in neurodegenerative disorders. In an attempt to isolate CAG repeat-containing cDNAs expressed in nervous tissue, we screened a human fetal brain cDNA library with a probe containing a CAG repeat. Five different clones were characterized and found to contain CAG repeats.

Familial anaplastic ependymoma: evidence of loss of chromosome 22 in tumour cells.

A family with anaplastic ependymomas, histologically verified in three cases and neuroradiologically suggested in a fourth, is presented. Two healthy brothers both had two affected sons. All four male patients were younger than 5 years at the time of diagnosis.

The prevalence of localized juvenile periodontitis in Saudi subjects.

The purpose of this study was to determine the prevalence and sex ratio of localized juvenile periodontitis (LJP) cases in a selected Saudi population, to compare these values with different societies, and to correlate the sex ratio with the presence of Actinobacillus actinomycetemcomitans in the afflicted sites. In a retrospective study over a 3-year period 23 cases of LJP were diagnosed from a group of 5,480 subjects with different forms of periodontal disease. The overall prevalence was 0.

Report of the New England Task Force on Reducing Heart Disease and Stroke Risk.

Five years ago, a task force on reducing risk for heart disease and stroke was established by the six New England States. The task force included representatives from State public health departments, academia, the corporate sector, and voluntary organizations. This article is the final report of the task force.