Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).

BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. AIM: To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. METHODS: Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. RESULTS: Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. CONCLUSIONS: Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].

Escobar syndrome with heterotaxia and esophageal atresia: case report.

Escobar syndrome (ES) or multiple pterygia syndrome (MIM#265000) is an infrequent condition characterized by facial dysmorphism, multiple webbing (pterygia), congenital contractures (arthrogryposis) and other internal anomalies. We describe an 8-days-old male newborn from consanguineous parents with ES who also presented heterotaxia syndrome and esophageal atresia, anomalies that not have been previously reported as associated to ES.

Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant.

Antidepressants and physical exercise have been shown to increase the transcription of hippocampal brain-derived neurotrophic factor (BDNF). Much evidence regarding the initial actions of antidepressant medications as well as exercise leads to the hypothesis that noradrenergic (NE) and/or serotonergic (5-HT) activation is a key element in the BDNF transcriptional elevation common to both interventions. Currently, we used short-term beta-adrenergic, 5-HT(1A), or 5-HT(2A/C) receptor blockade to characterize the influence of NE and 5-HT systems on BDNF transcription during physical exercise and antidepressant treatment. In situ hybridization revealed that beta-adrenergic blockade significantly blunted the BDNF mRNA elevations due to exercise, and also inhibited the modest elevations in the CA3 and dentate gyrus following short-term treatment with tranylcypromine. In contrast, 5-HT(2A/C) blockade only minimally altered exercise-induced BDNF mRNA levels, but inhibited up-regulation of BDNF transcription via tranylcypromine. Finally, 5-HT(1A) blockade did not inhibit exercise-induced BDNF mRNA elevations, but significantly enhanced levels above those achieved with exercise alone in the CA4. These results suggest that NE activation via beta-adrenergic receptors may be essential for both exercise and antidepressant-induced BDNF regulation. 5-HT(1A) and 5-HT(2A/C) activation, on the other hand, appear to be most important for antidepressant-induced BDNF regulation, but may also participate significantly in exercise-induced regulation in the CA4.

[Effect of weekly mouthrinses with 0.2% neutral NaF solution on caries incidence in first permanent molars]. / Efecto de enjuagatorios semanales con una solucion neutra de NaF al 0.2% en la incidencia de caries en primeros molares definitivos.

A 32-month study was undertaken to determine the caries inhibitory effect of a weekly rinse for one minute with a solution of 0.2% NaF on the first permanent molars. Subjects who participated in the study were 295 school children aged from 5 to 13 years who were divided by random selection in two groups, test and control who rinsed with either 0.2% NaF solution or a placebo under double-blind conditions. Reductions in caries increments on first permanent molars (20.7% DMFT and 31.9% DMFS) were seen in the test group as compared with the control group. A preventive effect was also seen in all first permanent molars surfaces, being the major protective effect in approximal surfaces (52% reduction) followed by occlusal (36%) and bucolingual surfaces (16%).