Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Comparison of Two Concentration Methods for the Molecular Detection of Enteroviruses in Raw and Treated Sewage.

Human enteric viruses are a major causative agent of emerging waterborne diseases and constitute a serious public health concern. Environmental contamination occurs through discharge of waste materials from infected persons. Methods for viral detection should be developed to detect low infective dose of enteric viruses in environment. In this study, we aimed at comparing two concentration methods for the detection of naturally occurring enteroviruses in raw and treated sewage. In the first method, polyethylene glycol is used to concentrate viral particles from the collected samples. The second method is based on ultracentrifugation of viral particles at high speed (110,000×g). Genomes of enteroviruses were quantified by the quantitative real-time PCR method in raw and treated sewage samples. PEG-based method yielded higher genomic copies of enteric viruses (with an average of 5.9 log10 genomic copies/100 mL) when applied to raw sewage samples. While the ultracentrifugation assay in the second method decreases genomic copies number (with an average of 5.4 log10 genomic copies/100 mL). The recovery differences between the two methods were not significant when applied to clean samples (treated sewage). This could be explained by the presence of inhibitors, which interfere with qRT-PCR, in less quantity comparatively to raw sewage. PEG-based method would be more accurate for samples with high-organic matter load. This report emphasizes the importance of matrices nature on the recovery of enteroviruses from sewage samples. This should be taken into consideration for establishing standardized virological assays to ensure the virological quality control of discharged water in environment.

Removal of Rotavirus and Bacteriophages by Membrane Bioreactor Technology from Sewage.

Human enteric viruses constitute a public health concern due to their low infectious dose and their resistance to environmental factors and to inactivation processes. We aimed at assessing the performance of a laboratory scale Submerged membrane bioreactor (SMBR) treating abattoir wastewaters for Rotavirus (RV) and total coliphages removal. We also aimed at evaluating removal efficiency of enteric viruses through conventional activated sludge treatment by measuring concentrations of total coliphages, considered as fecal and viral contamination indicators, with double-layer agar technique. The Log10 reduction values of bacteriophages ranged from 1.06 to 1.47. Effluents were analyzed to investigate and quantify RV, hepatitis A virus (HAV), Hepatitis E virus (HEV), Noroviruses genogroup I (NoV GI) and genogroup II (NoVGII), and Enterovirus (EV) by real-time PCR, using standardized detection kits (ceeramTools detection kits(®)). All effluent samples were positive for RV; concentrations ranged from 5.2 × 10(5) to 1.3 × 10(7) genome copies/L. These results highlight the inefficiency of conventional biological process for viral removal. A complete removal of RV during Membrane Bioreactor treatment was obtained. To the best of our knowledge, this is the first study providing an evidence of removal of RV simultaneously with total coliphages by SMBR.

Coronary calcified nodules versus nonnodular coronary calcifications: a systematic review and meta-analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) on severely calcified coronary lesions is challenging. Coronary calcified nodule (CN) refers to an eccentric and protruding coronary calcification associated with plaque vulnerability and adverse clinical events. This study aims to conduct an extensive review of CNs, focusing on its prognostic impact in comparison with nonnodular coronary calcification (N-CN). METHOD: A systematic literature review on PubMed, MEDLINE, and EMBASE databases was conducted for relevant articles. Observational studies or randomized controlled trials comparing CNs and N-CNs were included. RESULTS: Five studies comparing CNs and N-CNs were pertinent for inclusion. The total number of individuals across these studies was 1456. There were no significant differences in the baseline demographic, clinical, and angiographic data between the CN and N-CN groups. Intracoronary imaging was always utilized. At follow-up, CNs were associated with significantly increased, target vessel revascularization [odds ratio (OR) 2.16; 95% confidence interval (CI): 1.39-3.36, P-value < 0.01, I2 = 0%] and stent thrombosis (OR 9.29; 95% CI: 1.67-51.79, P-value = 0.01, I2 = 0%) compared with N-CN. A trend for greater cardiac death was also assessed in the CN group (OR 1.75; 95% CI: 0.98-3.13, P-value = 0.06, I2 = 0%). CONCLUSION: CN has a significantly negative impact on outcomes when compared with N-CN.

Seasonal changes in plasma steroid levels in relation to ovarian steroidogenic ultrastructural features and progesterone receptors in the house gecko, Hemidactylus flaviviridis, in Oman.

A comprehensive study of the annual ovarian cycle in the house gecko, Hemidactylus flaviviridis, was conducted in Oman. Circulating estradiol (E(2)), progesterone (P), and testosterone (T) were measured during the active and inactive phases of the cycle. The steroid levels were related to the steroidogenic ultrastructural features such as the abundance of smooth endoplasmic reticulum (SER), the presence of cisternal whorls, and close association of lipid droplets with swollen vesiculated mitochondria and SER. The steroids were measured using a sensitive detection technique HPLC-MS/MS. E(2) levels began to rise in January at the onset of vitellogenesis and continued to rise between February and May relative to ovulation, postovulation, gravidity and oviposition. Afterwards, E(2) remained low during the inactive phase (June-December). P levels increased significantly in March and peaked in April, which coincided with luteinization. P levels began to decline relative to luteolysis (May-June). Afterwards, it remained low throughout the inactive phase. T levels rose significantly in March-April coinciding with vitellogenesis, but decreased rapidly and significantly in May and remained low during the inactive phase. Progesterone receptors (PR), identified using immunohistochemistry, were strongly expressed during the breeding period, but were absent during the non-breeding period. The appearance of the steroidogenic ultrastructural features in the preovulatory and lutein granulosa cells was correlated with the significant rise in the three steroid levels and the PR. As the steroid levels declined, the granulosa cells underwent a general degeneration and disruption of the associated steroidogenic features.

[Hepatitis A virus detection in shellfish from Tunisia by reverse transcription-nested PCR--investigation of a correlation between viral and bacterial contamination]. / Détection du virus de l'hépatite A dans les coquillages en Tunisie par reverse transcription-nested PCR - recherche de corrélation entre la contamination virale et bactérienne.

OBJECTIVES: We aimed at evaluating the contamination by hepatitis A virus (HAV) of 54 shellfish samples collected from five Tunisian shellfish harvesting areas and finding a correlation between bacterial and viral contamination. MATERIAL AND METHODS: Fifty-four shellfish samples were analysed in our study. Two methods of viral extraction were evaluated by reverse transcription-nested PCR. The first one was based on elution by glycine solution and the second one used a beef extract solution. Bacteriological determination (Samonella and E. coli) was carried out for all shellfish samples. RESULTS: Glycine extraction showed a higher detection rate of HAV compared to the saline beef extraction method. The hepatitis A virus was detected in 32 % of shellfish samples analysed. None of the samples revealed the presence of Samonella. From 17 samples positive for HAV, we found six samples showing a number of E. coli below the European legislation. CONCLUSION: An important HAV contamination was observed in our study. No correlation between bacterial and viral contamination was found.

Analysis of elemental composition of the eggshell before and after incubation in the loggerhead turtle ( Caretta caretta) in Oman.

To date, there are limited studies on loggerhead turtle (Caretta caretta) eggshell ultrastructure and its elemental composition. Eggs were collected from turtle nests immediately after oviposition and post hatching. Three eggshell layers were recognized. The outer calcareous layer consists of loose nodular units of different shapes and sizes with loose attachment between the units, resulting in numerous spaces and openings. Each unit consists of CaCO3 crystals in aragonite (99%) and calcite (1%). The middle layer has several strata with numerous openings connecting the calcareous and the inner shell membrane. Crystallites of the middle layer are a mix of amorphous material with aragonite (62%) and calcite (38%). The inner shell membrane has numerous reticular fibers mixed predominantly with halite (NaCl) and small amounts of sylvite. Thermogravimetry analysis of the calcareous showed a low exothermic peak at 425°C, which corresponds to a transitional phase from aragonite to calcite. A high endothermic peak at 814°C corresponds to decomposition of calcite CaCO3 to CaO and CO2. Electron diffraction confirmed the presence of NaCl halite crystal. A significant difference was found in the percentage of elements and crystal configurations in the three layers. This study has value in assessing the emergence success in this endangered species.

[Clinical and genetic characteristics of Buschke-Fischer-Brauer's disease in a Tunisian family]. / Etude clinique et génétique de la kératodermie palmoplantaire de Buschke-Fischer-Brauer dans une famille tunisienne.

BACKGROUND: Punctate palmoplantar keratoderma (PPPK), or Buschke-Fischer-Brauer's disease, is a rare form of genodermatosis with autosomal dominant transmission and with variable penetrance. Its molecular basis remains unknown. Two loci were found to be linked to this disease: one on 15q22 and the other on 8q24. We report the clinical and genetic characteristics of PPPK in a Tunisian family. PATIENTS AND METHODS: A Tunisian family with PPPK was identified through a proband. As far as possible, history taking, physical examination, histopathological tests and blood sampling for DNA extraction were carried out for each patient. RESULTS: Seventeen patients were included in this study. Age ranged from 15 to 81 years with a sex-ratio of 3.2 m/f. Lesions appeared between the ages of 10 and 65 years and at a mean of 28 years. Clinically, lesions ranged from few keratotic papules on the palms to coalescence of lesions in plaques over palmar and/or plantar surfaces. Hyperhydrosis, hypopigmented macules and nail dystrophy were frequently associated. In all patients, histopathological examination revealed thickening of the epidermis with compact orthohyperkeratosis overlying a small and sharply demarcated area of depressed epidermis. Mechanical measures and keratolytic ointments proved non-beneficial. Genotyping for chromosomes 8 and 15 as well as LOD scores confirmed genetic linkage with the suspected locus on chromosome 15q, with the interval of the locus in question reduced to 3.26 Mb. This region is flanked by markers D15S987 and D15S153. CONCLUSION: Our study of this family confirmed the classical characteristics of KPP-BFB as well as demonstrating several associated clinical signs of which the significance will be determined in subsequent studies. Further screening studies to identify mutated genes in the region of interest will help us to understand the molecular basis of this disease and hopefully to propose suitable treatment.

Effect of low voltage electrical stimulation on biochemical and quality characteristics of Longissimus thoracis muscle from one-humped Camel (Camelus dromedaries).

The effects of electrical stimulation (90V) 20min post mortem on meat quality and muscle fibre types of four age group camels (1-3, 4-6, 7-9, 10-12 years) camels were assessed. Quality of the Longissimus thoracis at 1 and 7 days post mortem ageing was evaluated using shear force, pH, sarcomere length, myofibrillar fragmentation index, expressed juice, cooking loss and L(∗), a(∗), b(∗) colour values. Age of camel and electrical stimulation had a significant effect on meat quality of L. thoracis. Electrical stimulation resulted in a significantly (P<0.05) more rapid pH fall in muscle during the first 24h after slaughter. Muscles from electrically-stimulated carcasses had significantly (P<0.05) lower pH values, longer sarcomeres, lower shear force value, higher expressed juice and myofibrillar fragmentation index than those from non-stimulated ones. Electrically-stimulated meat was significantly (P<0.05) lighter in colour than non-stimulated based on L(∗) value. Muscles of 1-3 year camels had a significantly (P<0.05) lower shear force value, and pH, but longer sarcomere, and higher myofibrillar fragmentation index, expressed juice, and lightness colour (L(∗)) than those of the 10-12 years camels. The proportions of Type I, Type IIA and Type IIB were 25.0, 41.1 and 33.6%, respectively were found in camel meat. Muscle samples from 1-3 year camels had significantly (P<0.05) higher Type I and lower Type IIB fibres compared to those from 10-12 year camel samples. These results indicated that age and ES had a significant effect on camel meat quality.

[Results of percutaneous mitral balloon commissurotomy in pregnant women about 12 cases]. / Résultats de la dilatation mitrale percutanée chez la femme enceinte à propos de 12 cas.

INTRODUCTION: Mitral stenosis (MS) is the most common valvular heart disease revealed or exacerbated by pregnancy. Percutaneous mitral balloon commissurotomy (PMC) is currently the treatment of choice when mitral valve morphology is favorable. AIM OF THE STUDY: The purpose of this study is to evaluate the immediate, medium and long term results of percutaneous mitral balloon commissurotomy in pregnant women with a severe symptomatic mitral stenosis despite medical treatment. PATIENTS AND METHODS: It is a retrospective study including 12 pregnant patients diagnosed with severe mitral stenosis and hospitalized in the cardiology department of Habib Thameur hospital between 1994 and 2014. A clinical and ultrasonographic monitoring was performed for over 15 years. RESULTS: Mean patients age was 31.5±4.4 years. All patients were in NYHA class III or IV despite medical treatment. Mitral regurgitation was rated as moderate in four cases. Functional improvement was observed in all cases immediately after the procedure. Mitral valve area increased from 1.02±0.5cm2 averaged to 2±0.35cm2. Mitral regurgitation increased in three cases and appeared in two cases. All patients delivered at term. Newborns were all healthy. Two of them had a low birth weight. On the long term follow-up (95.58±64.1 months), five patients had mitral restenosis: two had a surgical valve replacement and three underwent a second percutaneous mitral balloon commissurotomy. CONCLUSION: The effectiveness of the percutaneous mitral balloon commissurotomy is clearly documented by clinical and echocardiographic evaluation. In the case of pregnancy, the goal is not so much to obtain an optimal result but to cause hemodynamic improvement authorizing the continuation of pregnancy and childbirth.

Activity antifungal of the essential oils; aqueous and ethanol extracts from Citrus aurantium L.

Our study is about the essential oil of Citrus aurantium L. in Tunisia and its plant extract. The yield of this essential oil is 0, 56% but the yield of the extract of plant was 17.1% for the aqueous extract ant 18.3% for the ethanolic extract. The analysis of chemical composition by using GC and GC/MS showed the essential oil of C. aurantium L. species to be rich in monoterpenes such as α-terpineol, lianolyl acetate, linalool and limonene. The antifungal activity of this oil showed us an inhibition of the germination of mushrooms, in the same way we could note that the biologic activities are generally assigned to the chemotypes high content in oxygenated monoterpene.

Utility decrements associated with side effects in schizophrenia.

OBJECTIVE: Most of the existing studies investigating the impact of schizophrenia on utility have focused on the different stages of the disease. The objective of this study was to describe and quantify the impact of treatment-related side-effects on utility in patients with schizophrenia, using data from an observational study. METHODS: This study used data from the European Schizophrenia Cohort (EuroSC), a multi-center 2-year cohort study conducted in France, England, and Germany. The EQ-5D questionnaire was completed every 6 months, as well as the Subjective Side Effect Rating Scale, assessing patient distress over extrapyramidal symptoms (EPS), weight gain, sedation, and sexual dysfunction, used to assess whether or not the patient experienced the side-effect. At first a bivariate analysis was conducted to describe utility values with and without side-effects. Then, a random effects regression analysis was performed on utility, where random effects were controlled for repeated measures on the same subjects, with potential confounding factors. Finally, findings were compared with those of previous publications. RESULTS: This sample consisted of 1208 patients with schizophrenia. At the baseline visit, the most reported side-effect was EPS (almost 60% of patients), followed by sedation and weight gain (∼50% of patients for each), and sexual dysfunction (almost 30% of patients). Significant association with severity of symptoms, functioning abilities, and utility were found. Patients reporting none of the studied side-effects had an average EQ-5D index score of 0.81, found to be higher than scores of patients reporting EPS (0.70), sexual dysfunction (0.67), sedation (0.70), or weight gain (0.72). The random effects model reported a utility decrement of 0.042 for EPS, 0.022 for weight gain, 0.022 for sexual dysfunction, and 0.019 for sedation. Although the external validation was difficult due to the different methods or definitions of the side-effects, as well as the paucity of data for weight gain, sedation and sexual dysfunction, the results were generally consistent with previous studies. CONCLUSION: This study aimed at quantifying the direct impact of main side-effects associated with antipsychotics on patients' utility. RESULTS suggested a significant direct impact of side-effects, with EPS being the most impactful.

Ultrastructural features and elemental distribution in eggshell during pre and post hatching periods in the green turtle, Chelonia mydas at Ras Al-Hadd, Oman.

Eggshells were randomly collected from turtle nests immediately after oviposition and at the end of incubation to examine the ultrastructural features using scanning JSM-5600LV microscopy. Three layers were recognized; an outer calcareous, a middle multistrata and an inner membrane. The calcareous layer had loose nodular units varying in shape and size without interlocking attachments. In freshly laid eggs, each nodular unit had spicules arranged in folded stacks. The spicules became unfolded during incubation, to form radiating configurations. Elemental composition and mapping of the layers were analyzed using energy dispersive spectroscopy (EDS). The elements were unevenly distributed throughout the eggshell and Ca(2+) decreased significantly after hatching. X-ray diffraction was used to identify the crystals of the eggshells. It revealed that nodular units of the calcareous were made up of CaCO(3), as aragonite (91%), calcite (6%) and vaterite (3%). The middle layer consisted of organic amorphous material with aragonite (89%) and calcite (11%). The shell membrane consisted of reticular fibers with crystals predominantly of NaCl halite. Thermogravimetry analysis of the calcareous layer indicated a complete evaporation of bonded H(2)O at 480 degrees C and CO(2) at 830 degrees C. Using the differential thermal analysis (DTA), aragonite was transformed to stable calcite at 425 degrees C.

Effects of electrical stimulation on histochemical muscle fiber staining, quality, and composition of camel and cattle Longissimus thoracis muscles.

The effects of electrical stimulation on muscle fiber type, meat quality, and composition of Longissimus thoracis muscles from one-humped camels and Dofari Omani cattle of a comparable age range were investigated. A low-voltage electrical stimulation with 90 V, 14 Hz (pulse of 7.5-millisecond duration every 70 milliseconds) 20 min postmortem was applied. Samples from the left muscle were collected from 20 (2 to 3 y) camels and 24 cattle (1 to 3 y). For chemical composition, muscle samples were dried in a freeze dryer, and then ground to determine moisture, protein, fat, and ash. Macro- and micro-minerals were determined using an Inductively Coupled Plasma Emission Spectrometer. Quality characteristics of the meat were evaluated using shear force value, pH, sarcomere, myofibrillar fragmentation index, expressed juice, cooking loss percent, and CIE L*, a*, b* color values. Electrical stimulation resulted in a significantly (P < 0.05) more rapid pH fall in the muscle during the first 24 h after slaughter in both species. Muscles from electrically stimulated carcasses had significantly (P < 0.05) lower ultimate pH, longer sarcomere, and lower shear force values than those from nonstimulated carcasses. Lightness (L*), myofibrillar fragmentation, and expressed juice were significantly (P < 0.05) higher for stimulated than for nonstimulated muscles. Muscles of camels had significantly (P < 0.05) higher expressed juice, cooking loss percent, redness color (a*), and lower fat, Mg, K, and P than those from cattle. Electrical stimulation improved quality characteristics of meat from both species. This indicates that meat quality of local camel and cattle can be improved by electrical stimulation and consequently improves their acceptability to consumers and better marketability.

Granuloma multiforme: first case report in Tunisia.

Granuloma multiforme is a rare granulomatous skin disease, usually reported in sub-Saharan African countries. The exact aetiology of granuloma multiforme is still unknown. We report the case of a patient who presented clinical and histopathological features of granuloma multiforme that can be considered the first described case in Tunisia.