This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.

No previous study has used proteomics to investigate the effects of exercise training on human skeletal muscle. Five recreationally active men completed a 6-wk training programme involving three sessions per week, utilising six 1-min bouts at maximum oxygen uptake (V O(2)max) interspersed with 4 min at 50% V O(2)max. Vastus lateralis was biopsied at standardised times before and after the training intervention. Protein expression profiling was performed using differential analysis of 2-DE gels; complemented with quantitative analysis (iTRAQ) of tryptic peptides from 1-DE gel lane-segments using LC-MALDI MS/MS. Interval training increased average V O(2)max (7%; p<0.001) and was associated with greater expression of mitochondrial components, including succinate dehydrogenase, trifunctional protein-alpha and ATP synthase alpha- and beta-chains. 2-DE resolved 256 spots, and paired t-tests identified 20 significant differences in expression (false discovery rate <10%). Each differentially expressed gene product was present as multiple isoelectric species. Therefore, the differences in spot expression represent changes in post-transcriptional or post-translational processing. In particular, modulation of muscle creatine kinase and troponin T were prominent. Pro-Q Diamond staining revealed these changes in expression were associated with phosphorylated protein species, which provides novel information regarding muscle adaptation to interval training.

Background Patients with heart failure (HF) develop abnormal pulmonary gas exchange; specifically they have an abnormal ventilation relative to metabolic demand (VE/VCO2, ventilatory efficiency) during exercise. The purpose of this investigation was to examine the factors that underlie the abnormal breathing efficiency in this population. Methods Fourteen controls and 33 moderate-severe HF patients, aged 52±12 and 54±8 years, respectively, performed submaximal exercise (~65% of maximum) on a cycle ergometer. Gas exchange and blood gas measurements were made at rest and during exercise. Submaximal exercise data were used to quantify the influence of hyperventilation (PaCO2) and dead space ventilation (VD) on VE/VCO2. Results The VE/VCO2 relationship was lower in controls (30±4) than HF (45±9, p<0.01). This was the result of hyperventilation (lower PaCO2) and higher VD/VT that contributed 40% and 47%, respectively, to the increased VE/VCO2 (p<0.01). The elevated VD/VT in the HF patients was the result of a tachypneic breathing pattern (lower VT, 1086±366 vs 2003±504 ml, p<0.01) in the presence of a normal VD (11.5±4.0 vs 11.9±5.7 L/min, p=0.095). Conclusions The abnormal ventilation in relation to metabolic demand in HF patients during exercise was due primarily to alterations in breathing pattern (reduced VT) and excessive hyperventilation.

Exercise training leads to further improvements in exercise capacity, hemodynamic measures, and QOL in addition to the improvements seen after CRT. Therefore, exercise training allows maximal benefit to be attained after CRT.

Duchenne muscular dystrophy (DMD) is a dystrophin-deficient lethal muscle disease. To date, the catastrophic muscle wasting phenotype has only been seen in dystrophin-deficient humans and dogs. While Duchenne-like symptoms have been observed in more than a dozen dog breeds, the mutation is often not known and research colonies are rarely established. Here we report an independent canine DMD model originally derived from the Pembroke Welsh corgi breed. The affected dogs presented clinical signs of muscular dystrophy. Immunostaining revealed the absence of dystrophin and up-regulation of utrophin. Histopathologic examination showed variable fiber size, central nucleation, calcification, fibrosis, neutrophil and macrophage infiltration and cardiac focal vacuolar degeneration. Carrier dogs also displayed mild myopathy. The mutation was identified as a long interspersed repetitive element-1 (LINE-1) insertion in intron 13 which introduced a new exon containing an in-frame stop codon. Similar mutations have been seen in human patients. A colony was generated by crossing carrier females with normal males. Affected puppies had a normal birth weight but they experienced a striking growth delay in the first 5 days. In summary, the new corgi DMD model offers an excellent opportunity to study DMD pathogenesis and to develop novel therapies.