A mouse model of Schwartz-Jampel syndrome reveals myelinating Schwann cell dysfunction with persistent axonal depolarization in vitro and distal peripheral nerve hyperexcitability when perlecan is lacking

Congenital peripheral nerve hyperexcitability (PNH) is usually associated with impaired function of voltage-gated K(+) channels (VGKCs) in neuromyotonia and demyelination in peripheral neuropathies. Schwartz-Jampel syndrome (SJS) is a form of PNH that is due to hypomorphic mutations of perlecan, the major proteoglycan of basement membranes. Schwann cell basement membrane and its cell receptors are critical for the myelination and organization of the nodes of Ranvier. We therefore studied a mouse model of SJS to determine whether a role for perlecan in these functions could account for PNH when perlecan is lacking. We revealed a role for perlecan in the longitudinal elongation and organization of myelinating Schwann cells because perlecan-deficient mice had shorter internodes, more numerous Schmidt-Lanterman incisures, and increased amounts of internodal fast VGKCs. Perlecan-deficient mice did not display demyelination events along the nerve trunk but developed dysmyelination of the preterminal segment associated with denervation processes at the neuromuscular junction. Investigating the excitability properties of the peripheral nerve suggested a persistent axonal depolarization during nerve firing in vitro, most likely due to defective K(+) homeostasis, and excluded the nerve trunk as the original site for PNH. Altogether, our data shed light on perlecan function by revealing critical roles in Schwann cell physiology and suggest that PNH in SJS originates distally from synergistic actions of peripheral nerve and neuromuscular junction changes.

Pregnancy and delivery outcomes of HIV infected women in Switzerland 2003-2008

Rates of vertical HIV transmission between mother and child are low, allowing many HIV positive women to have children with near impunity. In this study, data from the Swiss Mother and Child HIV Cohort Study were used to describe maternal characteristics and their association with pregnancy outcomes in HIV positive women.

Detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase: effect of a low-tube-voltage, high-tube-current CT technique--preliminary results

To intraindividually compare a low-tube-voltage (80 kVp), high-tube-current (675 mA) computed tomographic (CT) technique with a high-tube-voltage (140 kVp) CT protocol for the detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase.

Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study

Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons.

Longitudinal analysis of patterns and predictors of changes in self-reported adherence to antiretroviral therapy: Swiss HIV Cohort Study

Adherence to combination antiretroviral therapy (cART) is a dynamic process, however, changes in adherence behavior over time are insufficiently understood.

Randomized trial of a computerized coronary heart disease risk assessment tool in HIV-infected patients receiving combination antiretroviral therapy

Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients' risk for CHD.

Outcomes of antiretroviral therapy in the Swiss HIV Cohort Study: latent class analysis

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.

Can we improve partner notification rates through expedited partner therapy in the UK? Findings from an exploratory trial of Accelerated Partner Therapy (APT)

To develop two new models of expedited partner therapy for the UK, and evaluate them for feasibility, acceptability and preliminary outcome estimates to inform the design of a randomised controlled trial (RCT).

Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Methods Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period. Results From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56). Conclusions The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.