C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W)

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic β cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant

Metastatic myocardial abscess on the posterior wall of the left ventricle: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myocardial abscess is a rare and potentially fatal condition. Metastatic myocardial abscess in the setting of infective endocarditis has been infrequently reported in the medical literature. To the best of the authors' knowledge no case of myocardial abscess affecting the free wall of the left ventricle secondary to infective endocarditis of a right-sided heart valve has been reported previously.</p> <p>Case presentation</p> <p>We report a case of tricuspid valve endocarditis caused by <it>Staphylococcus aureus </it>and resulting in a myocardial abscess on the posterior wall of the left ventricle, far from the active valvular infection. We also briefly discuss the role of different investigation modalities including cardiac magnetic resonance imaging in diagnosing myocardial abscess.</p> <p>Conclusion</p> <p>Myocardial abscess is a life-threatening illness. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need multi-modality imaging. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention may save life in this otherwise fatal condition.</p

Congenital absence of inferior vena cava and thrombosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>A congenitally absent Inferior Vena Cava (IVC) is a rare anomaly that is recognised to be associated with idiopathic Deep Venous Thrombosis (DVT), particularly in the young. It may not be apparent until later in life. Retrospectively, as discussed in this case, there can be clues indicating the presence of such an anomaly from a young age. However, it is not clear whether early recognition of this condition would affect the prognosis and treatment.</p> <p>Case presentation</p> <p>A 54 year old gentleman was admitted with 3 weeks of abdominal pain and localised swelling over the right flank. Examination revealed palpable 'snake-like' tortuous, tender lumps on the abdominal wall. Past history revealed chronic non-healing venous leg ulcers, and varicose veins necessitating varicose vein ligation at a very young age. The ulcers eventually needed skin grafting.</p> <p>During this, current admission he was investigated and diagnosed with Deep Vein Thrombosis (DVT). CT scan, performed to search for intra-abdominal cancer, revealed absence of the Inferior Vena Cava with extensive thrombosed collaterals of the superficial abdominal and azygous veins and a congenitally atrophic left kidney.</p> <p>Conclusion</p> <p>This is a case of one of the oldest patient described in the literature to be diagnosed with absence of the IVC. It is thought that IVC anomalies are under-diagnosed, and may be commoner than once believed. However there were vital clues in his previous medical history suspicious for an underlying venous anomaly. Idiopathic DVT in a relatively young person with a past history of chronic leg ulceration or varicose veins should be investigated for congenital anomalies of the IVC. This is best achieved by CT scan of the abdomen.</p

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients