Peripheral vascular disease in women: Are we analyzing the costs correctly?

Women treated with a peripheral vascular intervention, on average, have more comorbidities and cost more per hospital admission than women treated with a percutaneous coronary intervention. The impact of critical limb ischemia on these results is likely significant, but not available in these data. Physicians need to be more aware of the differences in the risks and manifestations of cardiovascular disease in women.

TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function.

Bone is a dynamic tissue that depends on the intricate relationship between protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) for maintaining homeostasis. PTKs and PTPs act like molecular on and off switches and help modulate differentiation and the attachment of osteoclasts to bone matrix regulating bone resorption. The protein T cell ubiquitin ligand-2 (TULA-2), which is abundantly expressed in osteoclasts, is a novel histidine phosphatase. Our results show that of the two family members, only TULA-2 is expressed in osteoclasts and that its expression is sustained throughout the course of osteoclast differentiation, suggesting that TULA-2 may play a role during early as well late stages of osteoclast differentiation. Skeletal analysis of mice that do not express TULA or TULA-2 proteins (DKO mice) revealed that there was a decrease in bone volume due to increased osteoclast numbers and function. Furthermore, in vitro experiments indicated that bone marrow precursor cells from DKO mice have an increased potential to form osteoclasts. At the molecular level, the absence of TULA-2 in osteoclasts results in increased Syk phosphorylation at the Y352 and Y525/526 residues and activation of phospholipase C gamma 2 (PLCγ2) upon engagement of immune-receptor-tyrosine-based-activation-motif (ITAM)-mediated signaling. Furthermore, expression of a phosphatase-dead TULA-2 leads to increased osteoclast function. Taken together, these results suggest that TULA-2 negatively regulates osteoclast differentiation and function.

Strategies to Reduce Recurrent Shocks Due to Ventricular Arrhythmias in Patients with an Implanted Cardioverter-Defibrillator.

Ventricular arrhythmias are a therapeutic challenge, owing to their relatively unpredictable and deadly nature. Many patients are treated with an implantable cardioverter-defibrillator for either primary or secondary prevention of ventricular arrhythmias, meaning those who are at high risk of versus those who have experienced ventricular arrhythmias or sudden cardiac arrest, respectively. Despite the life-saving benefit, ICD comes with the risk of recurrent shocks for both appropriate and inappropriate rhythms. Patients with recurrent shocks have a poor quality of life and increased mortality rates. In this article, we review data for optimal device settings, medical management and radiofrequency ablation strategies to minimise the frequency of ICD shock, with a focus on treatment of ventricular arrhythmias, to reduce patient morbidity and mortality, and to maximise wellbeing and quality of life.