Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.

Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure-function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1.

Clinical Evaluation of Assays for Plasma Renin Activity and Aldosterone Measurement by Liquid Chromatography-Tandem Mass Spectrometry.

Background: Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy.

Methods: We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA).

Rare single gene disorders: estimating baseline prevalence and outcomes worldwide.

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families.

Observational studies on macroprolactin in a routine clinical laboratory.

Background: It is now recommended that all samples with raised prolactin should be examined for the presence of macroprolactin. We performed a retrospective review of our experience of macroprolactin to determine the incidence and the natural history of macroprolactin.

Methods: A retrospective study of macroprolactin was made in a large clinical laboratory.

Methods to estimate access to care and the effect of interventions on the outcomes of congenital disorders.

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders.

Social tenants' health: evaluating the effectiveness of landlord interventions.

Background: The National Health Service (NHS) scores well internationally on access to healthcare. But access has been measured on methods likely to undersample the more disadvantaged. Social landlords have access to more disadvantaged groups and may be able to improve health outcomes for their tenants and reduce their NHS usage by simple interventions.

Chromosomal disorders: estimating baseline birth prevalence and pregnancy outcomes worldwide.

Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions.

Bone-specific alkaline phosphatase by immunoassay or electrophoresis: their use in clinical practice.

Background: Measurement of bone-specific alkaline phosphatase (BALP) may be useful in diagnosing and monitoring metabolic bone disease. This study aimed to evaluate the BALP immunoassay and compare it with electrophoresis (densitometry) for the quantitation of BALP.

Methods: Metra BALP immunoassay kits were used for the method comparison.

CSF xanthochromia: correlation with brain imaging and its usefulness as an out-of-hours test.

Background: Subarachnoid haemorrhage (SAH) is a spontaneous bleed into the subarachnoid space which is investigated by CT head and cerebrospinal fluid (CSF) xanthochromia. The aim of this study was to compare CSF xanthochromia with brain imaging and evaluate the need for out of hours (OOH) testing for CSF xanthochromia.

Method: Discharge summaries and brain imaging of patients with positive xanthochromia screen were reviewed over 12 months retrospectively.

Chylothorax diagnosis: can the clinical chemistry laboratory do more?

Background: Chylothorax is a rare anatomical disruption of the thoracic duct associated with a significant degree of morbidity and mortality. Diagnosis usually relies upon lipid analysis and visual inspection of the pleural fluid. However, this may be subject to incorrect interpretation.

Role of advanced glycation end products in cardiovascular disease.

Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)].

Falling prevalence of beta-thalassaemia and eradication of malaria in the Maldives.

Carriers of haemoglobin disorders have protection against falciparum malaria. Therefore, where this is common, carrier prevalence rises until this selective advantage is offset by deaths of affected children. Theory predicts a corresponding fall in carrier frequency following malaria eradication, but this has not been reported in practice.

Does Hospital Competition Save Lives? Evidence from the English NHS Patient Choice Reforms.

Recent substantive reforms to the English National Health Service expanded patient choice and encouraged hospitals to compete within a market with fixed prices. This study investigates whether these reforms led to improvements in hospital quality. We use a difference-in-difference-style estimator to test whether hospital quality (measured using mortality from acute myocardial infarction) improved more quickly in more competitive markets after these reforms came into force in 2006.

Determination of pharmaceutical and personal care products in wastewater by capillary electrophoresis with UV detection.

Capillary electrophoresis (CE) offers a fast and cost-effective alternative analytical technique to LC-MS/MS for separation and quantitation of many PPCP compounds in wastewater. In this study, we have developed a method that can simultaneously analyze eight different PPCP compounds in untreated wastewater (ibuprofen, triclosan, carbamazepine, caffeine, acetaminophen, sulfamethoxazole, trimethoprim, and lincomycin), using capillary electrophoresis with UV detection (CE-UV). The method detection limit (MDL) ranged from 1.

Investigation of urinary pteridine levels as potential biomarkers for noninvasive diagnosis of cancer.

Background: Biomarkers are good potential tools for early cancer diagnosis. Here we have analyzed eight different pteridines in the urine samples of cancer patients and compared them with samples from healthy subjects. Pteridines are important cofactors in the process of cell metabolism, and they have recently become a focal point of cancer screening research because certain pteridine levels have been shown to reflect the presence of cancers.

The validation of an in vitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions.

Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs.

Optimization of urinary pteridine analysis conditions by CE-LIF for clinical use in early cancer detection.

The second leading cause of death in the US is cancer and early discovery of the disease has translated into reduced fatality rates. We have identified and performed a systematic investigation of a method for urinary pteridine analysis by using CE-LIF, which is believed to possess the potential to diagnose the presence of cancer even earlier than existing methodologies. Through system enhancements, we have been able to improve the resolution of the two least resolved sets of peaks (6,7-dimethylpterin versus 6-biopterin and D-(+)-neopterin versus 6-hydroxymethylpterin) from 0.

Adaptation to altitude as a vehicle for experiential learning of physiology by university undergraduates.

In this article, an experiential learning activity is described in which 19 university undergraduates made experimental observations on each other to explore physiological adaptations to high altitude. Following 2 wk of didactic sessions and baseline data collection at sea level, the group ascended to a research station at 12,500-ft elevation. Here, teams of three to four students measured the maximal rate of oxygen uptake, cognitive function, hand and foot volume changes, reticulocyte count and hematocrit, urinary pH and 24-h urine volume, athletic performance, and nocturnal blood oxygen saturation.