Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation

Syndapin I (PACSIN 1) is a synaptically enriched membrane tubulating protein that plays important roles in activity-dependent bulk endocytosis and neuronal morphogenesis. While syndapin I is an in vitro phosphoprotein, it is not known to be phosphorylated in neurons. Here, we report the identification of two phosphorylation sites, S76 and T181, of syndapin I from nerve terminals. Both residues are located at the N-terminal helix-capping motifs (N-Cap) of different α-helices in the F-BAR domain, important for F-BAR homodimer curvature and dimer-dimer filament assembly, respectively. Phospho-mimetic mutations of these residues regulate lipid-binding and tubulation both in vitro and in cells. Neither phosphosite regulated syndapin I function in activity-dependent bulk endocytosis. Rather, T181 phosphorylation was developmentally regulated and inhibited syndapin I function in neuronal morphogenesis. This suggests a novel mechanism for phosphorylation control of an F-BAR function through the regulation of α-helix interactions and stability within the folded F-BAR domain.     

Human-animal anthrax outbreak in the Luangwa valley of Zambia in 2011

There has been a reduction of incidences of anthrax in the developed countries but it is still a public health problem in the developing countries where communities live in interface areas with wildlife. An outbreak of anthrax in Hippopotamus amphibious was observed in Zambia. Following the death of hippopotamuses, suspected human cases were reported. The objective of this study was to isolate and confirm Bacillus anthracis and to determine the antimicrobial susceptibility for the management of the disease. Of the specimens collected, 29.4% (95% confidence interval [CI], 11.4-56.0) were from humans, 42.1% (95% CI, 21.1-66.0) were from hippopotamuses and 20.0% (95% CI, 6.61-44.3) from the soil were found to be positive were for B. anthracis. An antimicrobial susceptibility test revealed that all the isolates were found to be sensitive to the recommended antibiotics. The disease control was achieved by case management and by explaining to the communities that they should avoid contact with animals that die from unknown causes.     

Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive patients in sub-Saharan Africa

Background: Alcohol is heavily consumed in sub‐Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7‐, 14‐, and 21‐day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC‐AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC‐AUC of PEth versus any 21‐day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC‐AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.     

Modern management of acute myocardial infarction

Disruption of intracoronary plaque with thrombus formation provides the pathophysiologic foundation for acute coronary syndromes, which comprise ST-segment myocardial infarction, non-ST-segment myocardial infarction, and unstable angina. Management differs depending on whether ST-segment elevation is present, but the general principles of timely restoration of coronary blood flow and initiation of secondary prevention strategies are applicable to all patients. The purpose of this review is to discuss first the epidemiology, pathophysiology, and diagnosis of acute myocardial infarction. Risk stratification and therapy for patients with ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndromes are then reviewed along with diagnosis and management of the complications of myocardial infarction.     

Interventricular septal rupture caused by vehicular trauma

We report the case of a patient admitted at the emergency unit after a severe car accident. As ECG showed a ST segment elevation in all leads, the working diagnosis was coronary dissection. Coronary angiography revealed a large interventricular septal rupture, confirmed by echocardiography. After discussion and as haemodynamics permitted, 6 weeks of medical observation were decided. A surgical repair was then performed, and provided a perfect repair of the shunt. We discuss about the prevalence and management of this rare traumatic complication.     

Very Low Viral Load (VLVL) Relapse Following Treatment of Naïve Patients with Chronic Hepatitis C

Background

Sustained virologic response (SVR) to treatment of naïve patients with chronic hepatitis C (HCV) with pegylated interferon and ribavirin is 50–60%. Patients who relapse have a poor response to re-treatment. We report a group of relapse patients with SVR to low-dose re-treatment after 6 months.

Aim

Characterization of HCV relapse patients with very low viral load (VLVL) (HCV RNA <5,000 IU/ml) 6 months after stopping full-dose initial treatment.

Methods

We identified 120 consecutive naïve patients over 4 years treated with pegylated interferon alpha-2a and ribavirin with full-dose therapy for 24 weeks (non-genotype 1) or 48 weeks (genotype 1) with baseline liver biopsy and at least 6 months of follow-up after treatment. HCV RNA by PCR and hepatic blood tests were obtained monthly during treatment and at least 1, 3, and 6 months post treatment.

Results

Of the initially treated patients, 54.2% had SVR, 25% non-response and 20.8% relapsed. Four of 25 who relapsed (16%) and one similar patient referred to our program had HCV RNA <5,000 IU/ml 6 months after stopping treatment (VLVL relapse). Significant differences (P < 0.05) compared with the 21 other relapse patients included all five patients who were genotype 1; 4/5 had cirrhosis, baseline HCV RNA was lower, and all had SVR to less intensive re-treatment for 6 months.

Conclusion

VLVL relapse patients should be sought, because SVR to re-treatment is common despite genotype 1 cirrhosis.