Staphylococcus aureus virulence factors and disease

Staphylococcus aureus is a major cause of nosocomial infections worldwide, especially methicillin-resistant S. aureus. Patients subjected to broad-spectrum antibiotics and immunosuppressive therapies have higher risk of infection by this microorganism. S. aureus infection are often extremely difficult to treat due to the large population heterogeneity, phenotypic switching, intra-strain diversity, hypermutability and most importantly the small colony variants. It is very important to emphasise that host immune responses against persistent infections by S. aureus is insufficient resulting normally into chronic infections, which in turn can lead to life threatening situations. So, throughout this chapter we will focus on the principal aspects of S. aureus virulence will be focused

Retenção Escolar: Será o envolvimento dos alunos na escola um bom preditor?

O envolvimento dos alunos na escola tem sido associado ao grau de comprometimento com a escola e à motivação para aprender. Vários estudos apontam a falta de envolvimento dos alunos como estando associada ao baixo rendimento académico, a problemas de comportamento e ao abandono escolar. Esta investigação tem como objetivo averiguar se os alunos com retenção escolar no final do ano letivo foram os que manifestaram, no início desse ano escolar (final do primeiro período), menos envolvimento escolar comparativamente com os que não ficaram retidos. A amostra foi constituída por 330 alunos do 10 º ano de escolaridade, de uma Escola Secundária de Lisboa. Foi utilizada a escala de Envolvimento dos Alunos na Escola - E4D-EAE (Veiga, 2013, 2016). Os resultados indicaram que os alunos com retenção escolar no final do ano letivo revelaram no primeiro período níveis mais baixos de envolvimento escolar, a nível Afetivo, Cognitivo e Comportamental, não havendo diferenças na dimensão Agenciativa. Uma regressão logística revelou que, controlando a variável género e área curricular, a dimensão mais importante e preditora da retenção foi a dimensão Afetiva. Tais resultados corroboram estudos revistos e permitem conduzir à elaboração de referências de intervenção psico-educacional junto dos alunos.info:eu-repo/semantics/publishedVersio

A robust flow-based system for the spectrophotometric determination of Cr(VI) in recreational waters

A flow-based method for the spectrophotometric determination of chromium (VI) in recreational waters with different salinities was developed. Chromium can occur in the environment in different oxidation states with different related physiological properties. With regard to chromium, the speciation is particularly important, as the hexavalent chromium is considered to be carcinogenic. To achieve that purpose, the use of the diphenylcarbazide (DPC) selective colored reaction with the hexavalent chromium was the chosen strategy. The main objective was to develop a direct and simple spectrophotometric method that could cope with the analysis of different types of environmental waters, within different salinity ranges (fresh to marine waters). The potential interference of metal ions, that can usually be present in environmental waters, was assessed and no significant interferences were observed (<10%). For a complete Cr(VI) determination (three replicas) cycle, the corresponding reagents consumption was 75 µg of DPC, 9 mg of ethanol and 54 mg of sulfuric acid. Each cycle takes about 5 min, including the system clean-up. The limit of detection was 6.9 and 12.2 µg L−1 for waters with low and high salt content, respectively. The method was applied for the quantification of chromium (VI) in both fresh and marine water, and the results were in agreement with the reference procedure.info:eu-repo/semantics/publishedVersio

Identification of a Novel Modulator of Thyroid Hormone Receptor-Mediated Action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Seroepidemiology of Toxoplasma gondii in wild ruminants in Spain

Toxoplasmosis is a parasitic zoonosis caused by Toxoplasma gondii which infects warm-blooded species worldwide. Humans can be infected through ingestion of tissue cysts from raw or undercooked meat, including game meat. A nationwide large-scale cross-sectional study was conducted to assess exposure to T. gondii in seven wild ruminant species in Spain. A total of 2,040 serum samples from 77 sampling sites randomly distributed in the five bioregions (BRs) covering mainland Spain were tested for antibodies against T. gondii using the modified agglutination test. The overall seroprevalence was 22.0% (449/2,040). Seroprevalence by species in decreasing order was as follows: 39.6% (141/356) in roe deer (Capreolus capreolus), 37.1% (138/372) in fallow deer (Dama dama), 16.6% (92/553) in red deer (Cervus elaphus), 14.0% (26/186) in Southern chamois (Rupicapra pyrenaica), 11.5% (24/209) in mouflon (Ovis aries musimon), 7.8% (27/346) in Iberian wild goat (Capra pyrenaica) and 5.6% (1/18) in Barbary sheep (Ammotragus lervia). Seropositivity was detected in 74.0% (57/77) of the sampling sites. Results indicate widespread but not homogeneous exposure to T. gondii in wild ruminant populations in Spain during the last two decades and highlight differences related to animal species and spatial distribution of these species in this country; this implies potential consequences of T. gondii for animal health, conservation and public health

Seroepidemiology of Toxoplasma gondii in wild ruminants in Spain

Trabajo presentado a la: XII Reunión de Ungulados Silvestres Ibéricos (RUSI). Vila Real, Portugal. 1-2 octubre.Peer reviewe

Prevalence of vertebral fractures and their prognostic significance in the survival in patients with chronic kidney disease stages 3-5 not on dialysis

The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. 612 NDD 3-5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. VF were detected in 110patients(18%). Serumphosphatelevels(OR0.719,95%CI0.532to0.972,p = 0.032),ankle-brachial index 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009-3.898, p = 0.047) were an independent predictor of all-cause mortality. In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3-5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Metabolic consequences of the water we drink: a study based on field evidence and animal model experimentation

The effect of the chronic consumption of water contaminated with residual concentrations of DDT’s metabolites (DDD—dichlorodiphenyldichloroethane and DDE—dichlorodiphenyldichloroethylene) found in the environment were evaluated on the biometric, hematological and antioxidant system parameters of the hepatic, muscular, renal and nervous tissues of Wistar rats. The results showed that the studied concentrations (0.002 mg.L−1 of DDD plus 0.005 mg.L−1 of DDE) could not cause significant changes in the hematological parameters. However, the tissues showed significant alteration in the activity of the antioxidant system represented by the increase in the activity of the enzymes gluthathione S-transferases in the liver, superoxide dismutase in the kidney, gluthathione peroxidase in the brain, and several changes in enzymatic activity in muscle (SOD, GPx and LPO). The enzymes alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were also evaluated for the amino acids’ metabolism in the liver, with ALT showing a significant increase in the exposed animals. In the integrative analysis of biomarkers (Permanova and PCOA), the studied concentrations showed possible metabolic changes and damage to cellular structures evidenced by increased oxidative stress and body weight gain among the treated animals. This study highlights the need for further studies on the impact of banned pesticides still present in soils that may induce adverse effects in organisms that may prevail in future generations and the environment

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe