Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins

Brief report: Responses to rituximab suggest B cell-independent inflammation in cutaneous systemic lupus erythematosus

Objective The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses of skin to rituximab are variable. This study was undertaken to determine the phenotype of rituximab-responsive disease. Methods Eighty-two patients with SLE who were receiving rituximab were prospectively studied. Of these patients, 32 had significant skin involvement before or after treatment. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous lupus subtype was classified by a dermatologist as acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), or other skin diseases, with supportive photographs or biopsies where necessary. Results Of 26 patients with skin disease at baseline, 9 (35%) had a beneficial mucocutaneous response to rituximab at 6 months, with good responses in ACLE (6 of 14 patients [43%]), and poor responses in CCLE (0 of 8 patients) (P=0.034). Clinical response was associated with anti-RNP negativity (P=0.024) and anti-Ro negativity (P=0.031). Flares of SCLE and CCLE occurred in 12 patients who either had no skin disease or had ACLE at baseline (i.e., a switch in subtype). Concomitant antimalarials or conventional immunosuppressants were not associated with response or flare rate. Posttreatment biopsies confirmed typical active SLE histology in lesions occurring during B cell depletion. Conclusion Our findings indicate that the clinical response to rituximab in cutaneous manifestations of SLE depends on subtype. None of the CCLE patients responded, and new CCLE lesions were observed during B cell depletion, suggesting that initiation and activity of these lesions is not B cell dependent. Flares of a range of skin diseases after B cell depletion may indicate a change in immune regulation following B cell-targeted therapy

Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I

The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein

Holographic aspects of three dimensional QCD from string theory

We study two aspects of 3D QCD with massless fermions in a holographic set-up from string theory, based on D3/D7 branes; parity anomaly and baryons as baby Skyrmions. We first give a novel account of parity anomaly of 3D QCD with odd number of flavors from the IR holographic viewpoint by observing a subtle point in D7 brane embeddings with a given fixed UV theory. We also discuss its UV origin in terms of weakly coupled D-brane pictures. We then focus on the parity-symmetric case of even number of N_F flavors, and study baryons in the holographic model. We identify the monopoles of U(N_F) gauge theory dynamically broken down to U(N_F/2)x U(N_F/2) in the holographic 4 dimensional bulk as a holographic counter-part of 3D baby-Skyrmions for baryons in large N limit, and work out some details how the mapping goes. In particular, we show that the correct baryon charges emerge from the Witten effect with a space-varying theta angle.Comment: 33 pages, 10 figures; v2: references added with comments, typos corrected; v3: more references added; v4: holographic baryon profile and the analysis of its baryon charge is significantly revised, correcting errors in the previous discussio

Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance

BACKGROUND: Transmission of hepatitis C vims (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. METHODS: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. RESULTS: Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. CONCLUSION: One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Will the community nurse continue to function during H1N1 influenza pandemic: a cross-sectional study of Hong Kong community nurses?

<p>Abstract</p> <p>Background</p> <p>Healthcare workers have been identified as one of the high risk groups for being infected with influenza during influenza pandemic. Potential levels of absenteeism among healthcare workers in hospital settings are high. However, there was no study to explore the attitudes of healthcare workers in community setting towards the preparedness to the novel H1N1 influenza pandemic. The aim of this study was to explore the willingness of community nurses in Hong Kong to work during H1N1 influenza pandemic.</p> <p>Methods</p> <p>A cross-sectional survey was conducted among all 401 community nurses employed by the Hospital Authority in Hong Kong when the WHO pandemic alert level was 6.</p> <p>Results</p> <p>The response rate of this study was 66.6%. 76.9% participants reported being "not willing" (33.3%) or "not sure" (43.6%) to take care of patients during H1N1 influenza pandemic. The self-reported reasons for being unwilling to report to duty during H1N1 influenza pandemic were psychological stress (55.0%) and fear of being infected H1N1 influenza (29.2%). The reported unwillingness to report to duty was marginally significantly associated with the request for further training of using infection control clinical guideline (OR: 0.057; CI: 0.25-1.02). Those who reported unwillingness or not being sure about taking care of the patients during H1N1 influenza pandemic were more depressed (p < 0.001) and found work more emotionally stressful (p < 0.001).</p> <p>Conclusions</p> <p>Interventions to provide infection control training and address community nurses' psychological needs might increase their willingness to provide care to patients in the community during H1N1 influenza pandemic. This would help to ensure an effective and appropriate health system response during the H1N1 influenza pandemic.</p

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

&lt;p&gt;Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.&lt;/p&gt; &lt;p&gt;The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.&lt;/p&gt; &lt;p&gt;Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.&lt;/p&gt; &lt;p&gt;Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.&lt;/p&gt; &lt;p&gt;Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.&lt;/p&gt; &lt;p&gt;Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.&lt;/p&gt