A practical guide to genetic testing in endocrinology.

Rapid advances in sequencing technology have led to significant improvements in genomic analysis, resulting in increased understanding of the molecular basis of many endocrine conditions. Genomic testing for rare disease is being integrated into everyday clinical practice, as the importance of confirming a genetic diagnosis earlier in a patient's pathway helps direct their clinical care and specialized management. In England, the new nationally commissioned Genomic Medicine Service has started to deliver testing for rare and inherited disease and cancer somatic tissue via seven Genomic Laboratory Hubs.

Genetic testing for hereditary hyperparathyroidism and familial hypocalciuric hypercalcaemia in a large UK cohort.

Background: Primary hyperparathyroidism (PHPTH) is a common endocrine disorder and an estimated 10% of cases are hereditary, related to syndromes including; multiple endocrine neoplasia (MEN) type 1, MEN type 4, MEN2A and hereditary hyperparathyroidism-jaw tumour syndrome. Establishing the underlying genetic cause for PHPTH allows for personalized and cost-effective management. Familial hypocalicuric hypercalcaemia (FHH) is a benign disorder of hypercalcaemia associated with an inappropriately low urinary calcium excretion, which is quantified by the calcium creatinine clearance ratio (CCCR).

Formative Evaluation of the Central Coast Integrated Care Program (CCICP), NSW Australia.

Introduction: Integrated care has been posited as an important strategy for overcoming service fragmentation problems and achieving the Quadruple Aim of health care. This paper describes the Central Coast Integrative Care Program (CCICP) a complex, multi-component intervention addressing 3 target populations and more than 40 sub-projects of different scale, priority and maturity. Details are provided of the implementation including activities undertaken for each target population, in the context of the Central Coast Local Health District (CCLHD) strategies and priorities.

A collaborative approach to the implementation of a structured clinical handover tool (iSoBAR), within a hospital setting in metropolitan Western Australian: A mixed methods study.

The aim of this study was to determine the effectiveness of an education intervention for the implementation of the clinical handover tool iSoBAR, in an acute setting. A quantitative, descriptive survey design, using pre and post survey data before and after the implementation of an education intervention was used. Twenty nine nurses, doctors and allied health personnel employed at the study site participated in the study.

A Comparative Workforce Study of Midwives Practicing in the State of Texas.

Introduction: Access to quality care is a problem in Texas, an ethnically diverse state with large birth numbers. The state has over 300 areas designated as medically underserved, and a severe lack of obstetricians and midwives. Minimal data exist on midwifery's contribution, and no known study compares the work environment and clinical practice of the 2 state-recognized midwifery paths, licensed midwives (LMs) and certified nurse-midwives (CNMs).

Extending palliative care to patients with Parkinson's disease.

Patients with Parkinson's disease have an illness which shortens their life and involves a heavy symptom burden for patient and carer. This article discusses some common palliative care issues pertinent to patients with Parkinson's disease.

Novel use of amantadine: to treat hiccups.

Persistent hiccups may have a considerable impact on general health through disturbance of diet, sleep, and mood. They can cause exhaustion, malnutrition, dehydration, wound dehiscence, and even death in extreme cases. We report a complex clinical case of intractable hiccups in a patient with cancer of the pancreas and Parkinson's disease and some of the problems encountered when attempting symptom control.

A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol.

The title compound (+)-, required for production of transition state analogue inhibitors of enzymes involved in T-cell-dependent disorders, was synthesized in five steps. A 1,3-dipolar cycloaddition of the nitrone formed from formaldehyde and N-benzylhydroxylamine to diethyl maleate gave the racemic cis-isoxazolidine (+/-)-. Reduction of the N-O bond of this compound gave pyrrolidone (+/-)- in excellent yield.

Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes.

Butyrate is a histone deacetylase inhibitor (HDACi) with anti-neoplastic properties, which theoretically reactivates epigenetically silenced genes by increasing global histone acetylation. However, recent studies indicate that a similar number or even more genes are down-regulated than up-regulated by this drug. We treated hepatocarcinoma HepG2 cells with butyrate and characterized the levels of acetylation at DNA-bound histones H3 and H4 by ChIP-chip along the ENCODE regions.

The landscape of histone modifications across 1% of the human genome in five human cell lines.

We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including the ENCODE Consortium common cell lines GM06990 (lymphoblastoid) and HeLa-S3, as well as K562, HFL-1, and MOLT4, we identified clear patterns of histone modification profiles with respect to genomic features. H3K4me3, H3K4me2, and H3ac modifications are tightly associated with the transcriptional start sites (TSSs) of genes, while H3K4me1 and H4ac have more widespread distributions.

Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays.

We present a detailed in vivo characterization of hepatocyte transcriptional regulation in HepG2 cells, using chromatin immunoprecipitation and detection on PCR fragment-based genomic tiling path arrays covering the encyclopedia of DNA element (ENCODE) regions. Our data suggest that HNF-4alpha and HNF-3beta, which were commonly bound to distal regulatory elements, may cooperate in the regulation of a large fraction of the liver transcriptome and that both HNF-4alpha and USF1 may promote H3 acetylation to many of their targets. Importantly, bioinformatic analysis of the sequences bound by each transcription factor (TF) shows an over-representation of motifs highly similar to the in vitro established consensus sequences.