Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels.

The interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR-12 after treatment with 12 weeks of LDV/SOF ± RBV were selected from the ION-1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow-up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels. At the end of treatment compared to baseline, a significant reduction in apoAII levels (-14.97 ± 63.44 µg/mL, P = 0.0067) and apoE levels (-4.38 ± 12.19 µg/mL, P < 0.001) was noted. These declines from baseline in apoAII (-16.59 ±66.15 µg/mL, P = 0.0075) and apoE (-2.66 ± 12.64 µg/mL, P = 0.015) persisted at 4 weeks of post-treatment follow-up. In multivariate analysis, treatment with LDV/SOF + RBV was independently associated with reduction in apoE (beta = 5.31 µg/mL, P = 0.002) (compared to RBV-free LDV/SOF) (P < 0.05). In contrast, apoCII levels overall increased from baseline to end of treatment (+2.74 ±11.76 µg/mL, P = 0.03) and persisted at 4 weeks of follow-up (+4.46 ± 12.81 µg/mL from baseline, P = 0.0005). Subgroup analysis revealed an increase in apoCII during treatment only in patients receiving LDV/SOF without RBV (+5.52 ± 11.92 µg/mL, P = 0.0007) but not in patients receiving LDV/SOF + RBV (P = 0.638). Treatment with LDV/SOF ± RBV is associated with a persistent reduction in the apolipoprotein AII and E after achieving cure. These data suggest that treatment with LDV/SOF ± RBV may be associated with alterations in serum apolipoproteins which could potentially impact viral eradication.

Plasma levels of stromal cell-derived factor-1 (CXCL12) and circulating endothelial progenitor cells in women with idiopathic heavy menstrual bleeding.

STUDY QUESTION: Do plasma levels of stromal cell-derived factor-1 (CXCL12, sometimes termed SDF-1) and the numbers of circulating endothelial progenitor cells (EPCs), EPC colony-forming units (EPC-CFU) and mature endothelial cells (ECs) differ between women with idiopathic heavy menstrual bleeding of endometrial origin (HMB-E) and controls and are they related to plasma levels of other angiogenic growth factors? SUMMARY ANSWER: Angiogenesis is altered in women with HMB-E, characterized by a reduction in mean plasma levels of CXCL12, a low number of EPCs-CFUs and a high level of circulating ECs. WHAT IS KNOWN ALREADY: Plasma levels of CXCL12 are significantly higher during the proliferative than the secretory phase of the menstrual cycle in healthy women and exhibit a negative correlation with blood EPC-CFUs. STUDY DESIGN, SIZE, DURATION: A prospective cohort study in a university hospital setting. Between 2008 and 2009 10 HMB-E patients were recruited from Karolinska University Hospital. Ten healthy women were also included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ten healthy control women and 10 HMB-E patients, all with regular menstrual cycles, provided 4 blood samples during a single menstrual cycle: 2 in the proliferative phase, 1 at ovulation and 1 in the secretory phase. We assessed plasma levels of CXCL12, vascular endothelial growth factor A(165) (VEGFA), basic fibroblast growth factor (bFGF) and granulocyte and granulocyte-macrophage colony-stimulating factors by ELISA. We counted circulating EPC-CFUs by culture, and ECs and EPCs by flow cytometry and immunostaining for cell surface markers. MAIN RESULTS AND THE ROLE OF CHANCE: Plasma levels of CXCL12 were significantly lower in HMB-E patients compared with control women (P < 0.0001), with a significant decrease (P = 0.013) between the proliferative phase and ovulation. VEGFA showed a trend towards the same decreasing pattern as CXCL12, although not statistically significant (P = 0.086), whereas systemic VEGFA levels in control women remained unchanged across the different phases of the menstrual cycle (P = 0.473). HMB-E patients had a lower number of EPC-CFUs compared with control women (P = 0.014), with a positive correlation between the level of CXCL12 and EPC-CFUs (r = 0.428; P = 0.047). Whilst the level of circulating endothelial cells in HMB-E patients was higher than in control women, this did not reach statistical significance. In contrast, the levels of the hematopoietic/EPC marker CD34 were significantly lower in HMB-E patients than control women (P < 0.020). LIMITATIONS, REASONS FOR CAUTION: Small sample, unknown source of CXCL12, unknown balance between influx and efflux of EPCs from bone marrow and to the endometrium. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that CXCL12 may play an important role in physiological angiogenesis in the endometrium, and that low and dysregulated levels of CXCL12 in women with HMB-E could affect vessel quality, integrity and repair. STUDY FUNDING/COMPETING INTEREST(S): Financial support was provided through the regional agreement on medical training and clinical research (ALF) between the Stockholm County Council and Karolinska Institutet (number 20110258). This study was also supported by grants from the Swedish Labor Market Insurance. The authors have no conflict of interest to declare.

Septal perforation and bilateral partial middle turbinate necrosis after bilateral sphenopalatine artery ligation.

OBJECTIVE: To report previously unreported complications of bilateral sphenopalatine artery ligation. SUBJECTS AND METHODS: We present the case of a 45-year-old man who underwent bilateral sphenopalatine artery ligation to control intractable posterior epistaxis. After four months, he re-presented with nasal obstruction and crusting. RESULTS AND ANALYSIS: Examination under general anaesthesia showed posterior septal perforation and bilateral necrosis of the lower parts of the middle turbinates. The necrotic parts were excised. The patient had no more complaints. CONCLUSION: Following sphenopalatine artery occlusion, ischaemic necrosis is a potential risk in anatomical areas that receive their only arterial supply from this artery. The staging of bilateral sphenopalatine artery occlusion needs to be studied.

Associations of chronic hepatitis C with metabolic and cardiac outcomes.

BACKGROUND: Chronic hepatitis C virus (CH-C) infection is associated with metabolic conditions such as insulin resistance and type 2 diabetes (DM) and may increase the risk of cardiovascular diseases. AIM: To assess the association of CH-C with risk factors for cardiovascular diseases using US population data. METHODS: The National Health and Nutrition Examination Surveys (NHANES) collected between 1999 and 2010 were used. RESULTS: Of 19 741 participants considered eligible for the study. Of this cohort, 173 individuals (0.88%) had detectable HCV RNA and were considered to have CH-C. Compared with controls, CH-C patients were predominantly African American (23.5% vs. 10.5%, P < 0.0001), men (66.6% vs. 46.1%, P = 0.0001), more likely to be between 45 and 55 years of age (41.9% vs. 20.4%, P = 0.0001), had higher rate of insulin resistance (44.1% vs. 31.1%, P = 0.0301), hypertension (40.1% vs. 28.9%, P = 0.0201), and history of smoking (76.2% vs. 29.9%, P < 0.0001). In multivariate analysis, in addition to known risk factors for insulin resistance, CH-C was independently associated with the presence of insulin resistance [OR (95% CI) = 2.06 (1.19-3.57)], DM [OR = 2.31 (1.18-4.54)] and hypertension [OR = 2.06 (1.30-3.24)]. Independent predictors of cardiovascular diseases included older age, presence of obesity and smoking. CH-C was independently associated with congestive heart failure subtype of cardiovascular diseases but not ischaemic heart disease and stroke. CONCLUSION: Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

Ultrastructure and distribution of the taste buds in the buccal cavity in relation to the food and feeding habit of a herbivorous fish: Oreochromis niloticus.

The buccal cavity of an herbivorous fish Oreochromis niloticus was investigated by means of scanning electron microscopy. The buccal cavity distinguished into the roof and the floor. Three different types of taste buds (type I, II and III) are distributed in the buccal cavity. The proximal part of the buccal cavity bears relatively high epidermal papillae in which type I TBs was found. The middle region of the buccal cavity is mostly occupied by low epidermal papillae containing type II TBs. Type III TBs which are present within the metabranchial buccal cavity; never rise above the normal level of the epithelium. The different types of TBs are useful for ensuring full utilization of the gustatory ability of the fish. It is postulated that the TBs serve different functions: TBs type I and II may act as chemoreceptors and mechanoreceptors. TBs type III acts predominantly as a chemoreceptors. TBs of each type show two kinds of receptor villi within their receptor areas: tall villi and small villi. The surface of the lining epithelial cells shows a delicate microridge system. These structures protect against physical abrasion potentially caused during food maneuvering and swallowing. Furthermore, protection of the epithelium from abrasion is enhanced with goblet cells secretion.

Managing problems with tracheoesophageal puncture for alaryngeal voice rehabilitation.

OBJECTIVES: The tracheoesophageal puncture (TEP) technique and the insertion of its associated voice prostheses may give rise to adverse events. We present our experience with this technique, paying special attention to the incidence and management of these adverse events. STUDY DESIGN: A retrospective clinical analysis was undertaken. METHODS: Seventy-five laryngectomized patients underwent TEP for voice restoration. They were divided into two groups: group one, 43 patients with secondary TEP; and group two, 32 patients with primary TEP. Patient medical records were reviewed for data on the incidence, management and outcome of adverse events encountered during patients' follow up. RESULTS: Problems that arose in the patients were itemized as either early or late. The same patient could develop one or more problems in either group. The management of these problems, concerning the creation and maintenance of the TEP and associated prostheses, was noted. In group one, results were initially favourable in 91 per cent of patients and still positive in 81.4 per cent after three years. In group two, early results were favourable in all patients, and only two patients asked for late elective closure of the TEP (with a success rate of 93.7 per cent). CONCLUSIONS: Via an intensive and multidisciplinary approach to problems, most of the inevitable adverse events could be solved adequately, minimizing the discomfort of patients who had undergone laryngectomy and indwelling voice prosthesis insertion.

Effects of Rhizobium inoculation, organic and chemical fertilizers on yield and physical properties of faba bean seeds.

A field experiment was carried out to investigate the effect of Rhizobium inoculation, sulphur, nitrogen and chicken manure on yield, 100-seed weight, cookability, non-soakers, total defects and hydration coefficient of faba bean. The results showed that sulphur, nitrogen and chicken manure treatments significantly (p < or = 0.05) increased yield, 100-seed weight, non-soakers, and hydration coefficient, in the absence of Rhizobium inoculation. The results also showed that Rhizobium inoculation significantly (p < or = 0.05) increased yield, 100-seed weight, cookability, but decreased non-soakers. A positive correlation (r = 0.90) was observed between the non-soaker percent and the total defect percent. No correlation was found between non-soakers, hydration coefficient and cookability. The results of this investigation indicate that Rhizobium inoculation is a promising fertilizer because it is cheap, easy to handle and improves plant growth and seed quality. The efficiency of inoculation could be improved with the addition of biological, chemical or organic fertilizers. Generally, fertilization of faba bean with nitrogen, sulphur or chicken manure not only increased plant growth and yield, but also improved seed quality and nutritional value.

Rhizobium leguminosarum inoculation decreases damage to faba bean (Vicia faba) caused by broad bean mottle bromovirus and bean yellow mosaic potyvirus.

Faba bean (Vicia faba) plants were inoculated with rhizobia and then their sap was infected with broad bean mottle bromovirus (BBMV) or bean yellow mosaic potyvirus (BYMV) in a field experiment. Both viral infections significantly decreased shoot and root dry weight, number of nodules, nodule dry weight, numbers of flowers and pods/plant, total plant N, grain yield and N2 fixation. However, inoculation withRhizobium leguminosarum significantly increased all these parameters, both in healthy and virus-infected plants. Although BYMV was more destructive than BBMV, inoculation with rhizobia could be used, with other control measures, to limit damage by both viruses.

Adherence of Pseudomonas aeruginosa to tracheal epithelial cells of mink. Studies on bacterial hydrophobicity and elastase production.

Pseudomonas aeruginosa strains, producing variable elastase activity, were evaluated for adherence ability to mink tracheal epithelial cells. Attachment was studied in relation to surface hydrophobic properties of bacteria. Elastase production and bacterial hydrophobicity were measured during growth up to 48 hr. A high elastasolytic strain B1 adhered well; it exhibited a mean of 39.0 bacteria per epithelial cell. Adherence of the organisms was not correlated with the degree of hydrophobicity, since more hydrophobic strains do not adhere better. Bacterial surface becomes less hydrophobic during exponential growth-phase (up to 6 h). Hydrophobicity then slightly increases up to 48 h. No correlation between elastase production and changes in surface hydrophobicity was found, since treatment of washed bacteria from either early exponential or later decline-growth phases with different concentrations of elastase did not markedly affect bacterial hydrophobicity. The results indicate that strains with high or active elastase production adhered better than low or inactive elastase-producing strains. Furthermore, bacterial surface hydrophobicity does not seem to play a major role in adherence.