Population collapse of habitat-forming species in the Mediterranean: a long-term study of gorgonian populations affected by recurrent marine heatwaves.

Understanding the resilience of temperate reefs to climate change requires exploring the recovery capacity of their habitat-forming species from recurrent marine heatwaves (MHWs). Here, we show that, in a Mediterranean highly enforced marine protected area established more than 40 years ago, habitat-forming octocoral populations that were first affected by a severe MHW in 2003 have not recovered after 15 years. Contrarily, they have followed collapse trajectories that have brought them to the brink of local ecological extinction. Since 2003, impacted populations of the red gorgonian Paramuricea clavata (Risso, 1826) and the red coral Corallium rubrum (Linnaeus, 1758) have followed different trends in terms of size structure, but a similar progressive reduction in density and biomass. Concurrently, recurrent MHWs were observed in the area during the 2003-2018 study period, which may have hindered populations recovery. The studied octocorals play a unique habitat-forming role in the coralligenous assemblages (i.e. reefs endemic to the Mediterranean Sea home to approximately 10% of its species). Therefore, our results underpin the great risk that recurrent MHWs pose for the long-term integrity and functioning of these emblematic temperate reefs.

Strong linkages between depth, longevity and demographic stability across marine sessile species.

Understanding the role of the environment in shaping the evolution of life histories remains a major challenge in ecology and evolution. We synthesize longevity patterns of marine sessile species and find strong positive relationships between depth and maximum lifespan across multiple sessile marine taxa, including corals, bivalves, sponges and macroalgae. Using long-term demographic data on marine sessile and terrestrial plant species, we show that extreme longevity leads to strongly dampened population dynamics. We also used detailed analyses of Mediterranean red coral, with a maximum lifespan of 532 years, to explore the life-history patterns of long-lived taxa and the vulnerability to external mortality sources that these characteristics can create. Depth-related environmental gradients-including light, food availability, temperature and disturbance intensity-drive highly predictable distributions of life histories that, in turn, have predictable ecological consequences for the dynamics of natural populations.

Prevalence of human papillomavirus types associated with cervical lesions in Sergipe state, Northeastern Brazil: high frequency of a possibly carcinogenic type.

Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer and the prevalence of HPV types varies depending on the geographic region. Therefore, this study assessed the prevalence of HPV types in women with cervical lesions from Sergipe state, Northeastern Brazil. A cross-sectional study was conducted in women with cervical lesions from March to December 2014. These lesions were investigated by PCR and HPV types were identified by DNA sequencing. 432 patients were included, of which 337 patients tested positive for HPV. Eighteen different HPV types were detected, and high-risk HPV types were detected in 69.2%. HPV 16 (63.4%) was the most prevalent HPV type found, followed by HPV 66 (4.6%), HPV 18 (1.6%) and HPV 45 (1.4%). These results highlight the importance of the high prevalence of HPV 66, which is a possibly carcinogenic virus type not covered by the available vaccines. The prevalence of HPV 16 was high in the studied population, reaffirming the importance of young vaccination. However, the high prevalence of HPV 66 found in this study shows the importance of monitoring the diversity of HPV types in different populations and geographic regions to better understand the impacts of current HPV vaccines.

Determination of Anti-Anisakis Simplex Antibodies and Relationship with αß and γδ Lymphocyte Subpopulations in Patients with Crohn's Disease.

BACKGROUND: The etiology of Crohn's disease (CD) is still unknown although new theories are based on defects in innate immunity. We have previously shown a decrease in γδ T cells in CD patients. Previous studies have shown a high prevalence of anti-A. simplex immunoglobulins in CD patients. The diminution of γδ T cells in the peripheral blood and intestinal mucosa of CD patients may create a state of immunosuppression that would facilitate A. simplex infection. AIMS: To study the antibody responses to Anisakis antigens in Crohn's disease patients and its relationship with αß and γδ T cell subsets. METHODS: We recruited 81 CD patients and 81 healthy controls. αß and γδ T cell subsets and anti-A. simplex antibodies were measured. RESULTS: Levels of anti-A. simplex IgG and IgM were significantly increased in CD patients. Almost 20% of CD patients were positive for IgG and IgM anti-A. simplex versus only 3.7 and 2.5%, respectively, in normal subjects. However, lower specific IgA levels were observed in the group of CD patients versus healthy subjects. We found an association between CD3 + CD8 + Î³Î´ subset and IgM anti-A. simplex levels. In ileal cases and stricturing behavior of CD, we observed the highest levels of specific antibodies with the exception of anti-A. simplex IgA. CONCLUSIONS: The relationship of specific antibodies with a γδ T cell deficiency makes these cell candidates to play a role in the immune response against Anisakis. In addition, anti-Anisakis antibodies could be considered as markers of risk of progression in CD.

Differential atrial performance at rest and exercise in athletes: Potential trigger for developing atrial dysfunction?

Highly trained athletes show an increased risk of atrial arrhythmias. Little is known about atrial volumes and function during exercise in this population. Our aim was to analyze atrial size and contractile function during exercise. Fifty endurance athletes with 11 ± 8 h of training per week and 30 sedentary control subjects were included. Echocardiography was performed at baseline and during exercise. Left (LA) and right atrial (RA) size and function were assessed by two-dimensional echocardiography. Peak negative strain (Sa) during atrial contraction and active atrial emptying volume (AEV) were measured. Athletes and control subjects showed a significant increment of deformation and AEV of both atria with exercise (P < 0.01 vs baseline for LA and RA). Among athletes, a subgroup with significant LA (n = 8)/RA (n = 15) dilatation (≥40 mL/m2 ) showed a significantly lower increment in AEV with exercise (LA∆AEV: 1.4 ± 1.1 mL/m2 vs 2.1 ± 0.9 mL/m2 , P = 0.04; RA∆AEV: 0.9 ± 0.8 mL/m2 vs 2.3 ± 1.1 mL/m2 , P < 0.01) and lower increment in deformation vs other athletes (LA∆Sa: -3.2 ± 2.9% vs -9.5 ± 4.4%, P < 0.01; RA∆Sa: -2.5 ± 3.3% vs. -9.8 ± 3.3%, P < 0.01). During exercise, active atrial strain increases, but less in athletes compared to controls, but due to larger atrial volumes, they reached similar increases in atrial emptying volume. However, this overall lesser deformation increases from a subgroup with significant atrial dilatation showing impairment in atrial contractile reserve.

Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93-6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.

In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus.

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection. This study evaluated the in vitro activity, selectivity, and resistance profile of a novel anti-HCV compound, samatasvir (IDX719), alone and in combination with other antiviral agents. Samatasvir was effective and selective against infectious HCV and replicons, with 50% effective concentrations (EC50s) falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50 shift in the presence of 40% human serum in the genotype 1b replicon. The EC90/EC50 ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 µM provided a selectivity index of >5 × 10(7). Resistance selection experiments (with genotype 1a replicons) and testing against replicons bearing site-directed mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30, 31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects NS5A function. Samatasvir demonstrated an overall additive effect when combined with interferon alfa (IFN-α), ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir retained full activity in the presence of HIV and hepatitis B virus (HBV) antivirals and was not cross-resistant with HCV protease, nucleotide, and nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low-picomolar inhibitor of HCV replication in vitro and is a promising candidate for future combination therapies with other direct-acting antiviral drugs in HCV-infected patients.

Evaluation of genotoxic and cytotoxic effects of antileishmanial extract from Julocroton triqueter (Euphorbiaceae).

Julocroton triqueter extracts have antileishmanial activity; however, the effect on genetic stability has not been studied. We evaluated genotoxic and cell death induction potential (in vitro and in vivo) of J. triqueter var. triqueter hydroalcoholic extracts, as well as their antigenotoxic potential in vivo. The in vitro genotoxic studies were performed using human leukocytes at four different concentrations. For the in vivo tests, Swiss mice were treated with 125, 250 or 500 mg/kg of extract injected intraperitoneally. Antigenotoxic effects of the extract were measured before and after cyclophosphamide treatment. An absence of genotoxic effects was observed both in vitro and in vivo. In the antigenotoxic studies, no significant difference was observed between the treatments and the positive control, indicating that the extracts did not protect against damage caused by cyclophosphamide. Hydroalcoholic extracts of J. triqueter did not provoke DNA damage at concentrations and doses normally used for antileishmanial treatment; however, they reduced apoptotic cell death and induced necrotic cell death.

Sedative effects of dexmedetomidine, dexmedetomidine-pethidine and dexmedetomidine-butorphanol in cats.

The purpose of this study was to assess the clinical effects of dexmedetomidine, both alone and combined with pethidine or butorphanol, in cats. A prospective randomized blind study was performed. Thirty cats were randomly assigned to three groups of 10 animals: D: dexmedetomidine (20 µg/kg IM); DP: dexmedetomidine (10 µg/kg IM) and pethidine (2.5 mg/kg IM); DB: dexmedetomidine (10 µg/kg IM) and butorphanol (0.4 mg/kg IM). Quality of sedation, analgesia, muscle relaxation and the possibility of performing some clinical procedures were compared using a multifactorial scale. Sedation, analgesia and muscle relaxation increased progressively over time and did not differ in the three protocols. The three protocols facilitated the completion of several clinical procedures. The clinical variables studied showed a similar behaviour in the three protocols and remained close to the baseline, except for a drop in heart rate in protocol D. In conclusion, dexmedetomidine, either alone or combined with pethidine or butorphanol, offers suitable sedation, analgesia and relaxation to perform various clinical procedures in cats.

Concordance of LDL-C Estimating Equations with Direct Enzymatic Measurement in Diabetic and Prediabetic Subjects.

Low-density lipoprotein cholesterol (LDL-C) is a well-established biomarker in the management of dyslipidemia. Therefore, we aimed to evaluate the concordance of LDL-C-estimating equations with direct enzymatic measurement in diabetic and prediabetic populations. The data of 31,031 subjects included in the study were divided into prediabetic, diabetic, and control groups according to HbA1c values. LDL-C was measured by direct homogenous enzymatic assay and calculated by Martin-Hopkins, Martin-Hopkins extended, Friedewald, and Sampson equations. The concordance statistics between the direct measurements and estimations obtained by the equations were evaluated. All equations evaluated in the study had lower concordance with direct enzymatic measurement in diabetic and prediabetic groups compared to the non-diabetic group. Even so, the Martin-Hopkins extended approach demonstrated the highest concordance statistic in diabetic and prediabetic patients. Further, Martin-Hopkins extended was found to have the highest correlation with direct measurement compared with other equations. Over the 190 mg/dL LDL-C concentrations, the equation with the highest concordance was again Martin-Hopkins extended. In most scenarios, the Martin-Hopkins extended performed best in prediabetic and diabetic groups. Additionally, direct assay methods can be used at low values of the non-HDL-C/TG ratio (<2.4), as the performance of the equations in LDL-C estimation decreases as non-HDL-C/TG decreases.

Polarimetric observables for the enhanced visualization of plant diseases.

This paper highlights the potential of using polarimetric methods for the inspection of plant diseased tissues. We show how depolarizing observables are a suitable tool for the accurate discrimination between healthy and diseased tissues due to the pathogen infection of plant samples. The analysis is conducted on a set of different plant specimens showing various disease symptoms and infection stages. By means of a complete image Mueller polarimeter, we measure the experimental Mueller matrices of the samples, from which we calculate a set of metrics analyzing the depolarization content of the inspected leaves. From calculated metrics, we demonstrate, in a qualitative and quantitative way, how depolarizing information of vegetal tissues leads to the enhancement of image contrast between healthy and diseased tissues, as well as to the revelation of wounded regions which cannot be detected by means of regular visual inspections. Moreover, we also propose a pseudo-colored image method, based on the depolarizing metrics, capable to further enhance the visual image contrast between healthy and diseased regions in plants. The ability of proposed methods to characterize plant diseases (even at early stages of infection) may be of interest for preventing yield losses due to different plant pathogens.

Exploring the response of a key Mediterranean gorgonian to heat stress across biological and spatial scales.

Understanding the factors and processes that shape intra-specific sensitivity to heat stress is fundamental to better predicting the vulnerability of benthic species to climate change. Here, we investigate the response of a habitat-forming Mediterranean octocoral, the red gorgonian Paramuricea clavata (Risso, 1826) to thermal stress at multiple biological and geographical scales. Samples from eleven P. clavata populations inhabiting four localities separated by hundreds to more than 1500 km of coast and with contrasting thermal histories were exposed to a critical temperature threshold (25 °C) in a common garden experiment in aquaria. Ten of the 11 populations lacked thermotolerance to the experimental conditions provided (25 days at 25 °C), with 100% or almost 100% colony mortality by the end of the experiment. Furthermore, we found no significant association between local average thermal regimes nor recent thermal history (i.e., local water temperatures in the 3 months prior to the experiment) and population thermotolerance. Overall, our results suggest that local adaptation and/or acclimation to warmer conditions have a limited role in the response of P. clavata to thermal stress. The study also confirms the sensitivity of this species to warm temperatures across its distributional range and questions its adaptive capacity under ocean warming conditions. However, important inter-individual variation in thermotolerance was found within populations, particularly those exposed to the most severe prior marine heatwaves. These observations suggest that P. clavata could harbor adaptive potential to future warming acting on standing genetic variation (i.e., divergent selection) and/or environmentally-induced phenotypic variation (i.e., intra- and/or intergenerational plasticity).

The crystal structure of Streptococcus pyogenes uridine phosphorylase reveals a distinct subfamily of nucleoside phosphorylases.

Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 Å resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an α/ß monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is ∼7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

Genetic structure in the Mediterranean seagrass Posidonia oceanica: disentangling past vicariance events from contemporary patterns of gene flow.

The Mediterranean Sea is a two-basin system, with the boundary zone restricted to the Strait of Sicily and the narrow Strait of Messina. Two main population groups are recognized in the Mediterranean endemic seagrass Posidonia oceanica, corresponding to the Western and the Eastern basins. To address the nature of the East-West cleavage in P. oceanica, the main aims of this study were: (i) to define the genetic structure within the potential contact zone (i.e. the Strait of Sicily) and clarify the extent of gene flow between the two population groups, and (ii) to investigate the role of present water circulation patterns vs. past evolutionary events on the observed genetic pattern. To achieve these goals, we utilized SSR markers and we simulated, with respect to current regime, the possible present-day dispersal pattern of Posidonia floating fruits using 28-day numerical Lagrangian trajectories. The results obtained confirm the presence of the two main population groups, without any indices of reproductive isolation, with the break zone located at the level of the Southern tip of Calabria. The populations in the Strait of Sicily showed higher affinity with Western than with Eastern populations. This pattern of genetic structure probably reflects historical avenues of recolonization from relict glacial areas and past vicariance events, but seems to persist as a result of the low connectivity among populations via marine currents, as suggested by our dispersal simulation analysis.

Crohn's disease and Sweet's syndrome: an uncommon association.

Sweet's syndrome or acute febrile neutrophilic dermatosis (SS) is characterized by the sudden onset of painful erythematous lesions (papules, nodules, and plaques) together with fever and neutrophilia. The lesions are typically located on hands, arms, upper trunk, neck and face, showing an asymmetric distribution. Acute phase reactants are usually elevated and dermal infiltration of neutrophils without vasculitis is seen on skin biopsies. It is considered as a marker of systemic disease in over half of the cases, and is associated with infections, inflammatory bowel disease, autoimmune connective tissue disorders and various neoplasias. Its association with Crohn's disease (CD) is unusual and it appears mainly in association with colonic involvement. Fewer than 50 cases have been published in the medical literature since its first description in 1964, some concurrent with the first episode of CD. We present two patients with Crohn's disease and Sweet's syndrome diagnosed in our department at the time of CD diagnosis, as well as their response to treatment, subsequent course of the disease, and a review of the scientific literature.

Gammadelta T cells as a predictor of surgical relapse of Crohn's disease.

BACKGROUND: We recently demonstrated a decrease in the overall lymphocyte population in the peripheral blood of patients with CD compared to healthy controls and this decrease is more evident in γδ T lymphocytes. The percentages of T cell subsets could reflect the risk of surgical relapse in CD patients. The aim of this study is to study the correlation between αß and γδ T cell subsets in the peripheral blood of patients with CD and the risk for surgery during follow up. METHODS: A prospective study of 102 patients with CD compared with 102 healthy subjects (control group) matched by age and sex was conducted. Lymphocytic populations of CD3+, CD4+, CD8+, CD56+, and αß and γδ T cell subsets were measured in the peripheral blood of all participants. RESULTS: We found evidence of a relationship between lower γδ T cell levels and risk of surgical relapse in CD. The lowest subsets observed in CD patients with surgical relapse were CD3+γδ, CD3+CD8+γδ and CD3+CD56+γδT cells. We observed a relationship between a decrease in γδ T cells and the most severe forms of the disease. The lowest levels of CD3+γδ and CD3+CD8+γδT cells were observed in the fistulizing phenotype. CONCLUSIONS: The deficit of γδ T cells was related with the severity and the risk for surgical relapse in CD patients. Patients with CD3+γδ deficit were more prone to surgery than patients without this deficit. These results suggest that γδ T cells could be used as markers of poor prognosis of CD following the diagnosis of the disease.

Cloud-cloud collision as drivers of the chemical complexity in Galactic Centre molecular clouds.

G+0.693-0.03 is a quiescent molecular cloud located within the Sagittarius B2 (Sgr B2) star-forming complex. Recent spectral surveys have shown that it represents one of the most prolific repositories of complex organic species in the Galaxy. The origin of such chemical complexity, along with the small-scale physical structure and properties of G+0.693-0.03, remains a mystery. In this paper, we report the study of multiple molecules with interferometric observations in combination with single-dish data in G+0.693-0.03. Despite the lack of detection of continuum source, we find small-scale (0.2 pc) structures within this cloud. The analysis of the molecular emission of typical shock tracers such as SiO, HNCO, and CH3OH unveiled two molecular components, peaking at velocities of 57 and 75 km s-1. They are found to be interconnected in both space and velocity. The position-velocity diagrams show features that match with the observational signatures of a cloud-cloud collision. Additionally, we detect three series of class I methanol masers known to appear in shocked gas, supporting the cloud-cloud collision scenario. From the maser emission we provide constraints on the gas kinetic temperatures (∼30-150 K) and H2 densities (104-105 cm-2). These properties are similar to those found for the starburst galaxy NGC253 also using class I methanol masers, suggested to be associated with a cloud-cloud collision. We conclude that shocks driven by the possible cloud-cloud collision is likely the most important mechanism responsible for the high level of chemical complexity observed in G+0.693-0.03.

Gas phase Elemental abundances in Molecular cloudS (GEMS) II. On the quest for the sulphur reservoir in molecular clouds: the H2S case.

CONTEXT: Sulphur is one of the most abundant elements in the Universe. Surprisingly, sulphuretted molecules are not as abundant as expected in the interstellar medium and the identity of the main sulphur reservoir is still an open question. AIMS: Our goal is to investigate the H2S chemistry in dark clouds, as this stable molecule is a potential sulphur reservoir. METHODS: Using millimeter observations of CS, SO, H2S, and their isotopologues, we determine the physical conditions and H2S abundances along the cores TMC 1-C, TMC 1-CP, and Barnard 1b. The gas-grain model Nautilus is used to model the sulphur chemistry and explore the impact of photo-desorption and chemical desorption on the H2S abundance. RESULTS: Our modeling shows that chemical desorption is the main source of gas-phase H2S in dark cores. The measured H2S abundance can only be fitted if we assume that the chemical desorption rate decreases by more than a factor of 10 when n H > 2 × 104. This change in the desorption rate is consistent with the formation of thick H2O and CO ice mantles on grain surfaces. The observed SO and H2S abundances are in good agreement with our predictions adopting an undepleted value of the sulphur abundance. However, the CS abundance is overestimated by a factor of 5 - 10. Along the three cores, atomic S is predicted to be the main sulphur reservoir. CONCLUSIONS: The gaseous H2S abundance is well reproduced, assuming undepleted sulphur abundance and chemical desorption as the main source of H2S. The behavior of the observed H2S abundance suggests a changing desorption efficiency, which would probe the snowline in these cold cores. Our model, however, highly overestimates the observed gas-phase CS abundance. Given the uncertainty in the sulphur chemistry, we can only conclude that our data are consistent with a cosmic elemental S abundance with an uncertainty of a factor of 10.

Hyaluronic acid, transforming growth factor-beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection.

Chronic hepatitis C virus (HCV) infection follows an accelerated course in patients co-infected with human immunodeficiency virus (HIV); establishing the extent of liver fibrosis is crucial for disease staging and determining treatment strategy in these patients. The utility of noninvasive markers of fibrosis as alternatives to liver biopsy has not been well-studied in these patients. We evaluated the predictive value of serum transforming growth factor-beta1 (TGF-beta1) and hyaluronic acid (HA) levels for determining the extent of liver fibrosis. Liver biopsies and blood samples were collected from 69 consecutive patients (74% male; median age, 41 years) between May 2005 and November 2006. Serum TGF-beta1 and HA were analysed using commercial kits. Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase levels were elevated in 81%, 70% and 60% of patients, respectively. Fifty-three patients (90%) were on highly active antiretroviral therapy and the median CD4-positive cell count was 422 cells/microL. The extent of fibrosis according to Scheuer's scoring was 32% F0 (no fibrosis), 16.5% F1, 16.5% F2, 26% F3 and 7% F4 (cirrhosis). Mean serum TGF-beta1 was 36.1 +/- 14.4 ng/mL; mean serum HA was 75.2 +/- 85.0 microg/L. Serum HA was positively associated and significantly correlated with the stage of fibrosis (r = 0.56; P < 0.05). The area under the curve for discriminating mild (F0-F2) from significant (F3-F4) fibrosis in receiver operating analysis using HA was 0.83 (sensitivity, 87%; specificity, 70%). These data suggest that HA is clinically useful for predicting liver fibrosis and cirrhosis in patients co-infected with HCV/HIV. However, serum TGF-beta1 was not predictive of histological damage in co-infected individuals treated with HAART.