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Objective: To compare the effects of a neuromuscular exercise program (ENM) with respect to a municipal exercise program (EM) on the physical condition of older adults in the community. Methodology: Double blind, parallel group randomized clinical trial. Sample ma de up of 82 subjects, age X = 72 years (SD = +/- 5 years) belonging to the House for the Elderly in the city of Talca. Selection was non-probabilistic for convenience, group assignment by stratified randomization, and allocation concealment by sealed envelopes. Double blinding was for participants and assessors. Both groups exercised in parallel for 6 months, 3 times a week. The inter-group comparisons of physical condition were by means of one-way multivariate ANOVA. In all cases a p

Despite mounting evidence that dark matter (DM) exists in the Universe, its fundamental nature remains unknown. We present sensitivity estimates to detect DM particles with a future very-high-energy ($\gtrsim$ TeV) wide field-of-view gamma-ray observatory in the Southern Hemisphere, currently in its research and development phase under the name Southern Wide field-of-view Gamma-ray Observatory (SWGO). This observatory would search for gamma rays from the annihilation or decay of DM particles in many key targets in the Southern sky, such as the Galactic halo, several dwarf galaxies, including the promising Reticulum II, and the Large Magellanic Cloud. With a wide field of view and long exposures, such observatory will have unprecedented sensitivity to DM in the mass range of $\sim$100 GeV to a few PeV from observations of a large fraction of the Galactic halo around the Galactic Center and from Galactic subhalos targets. These results, combined with those from other present and future gamma-ray observatories, will likely probe the thermal relic annihilation cross section of Weakly Interacting Massive Particles for all masses from $\sim$80 TeV down to the GeV range in most annihilation channels.

We propose to apply the entropy generation $(\dot S_{gen}$) concept to a mechanical system: the well-known simple pendulum. When considering the ideal case, where only conservative forces act on the system, one has $\dot S_{gen}=0$, and the entropy variation is null. However, as shall be seen, the time entropy variation is not null all the time. Considering a non-conservative force proportional to the pendulum velocity, the amplitude of oscillations decreases to zero as $t$ grows. In this case, $\dot S_{gen}>0$ indicates that it is related to energy dissipation, as stated by the Gouy-Stodola theorem. Hence, as shall be seen, the greater the strength of the non-conservative force, the greater are both the energy dissipation and the time rate of entropy variation.

8th World Conference on Photovoltaic Energy Conversion; 1486-1489, The actual climate crisis generated by the global warming requires a strong civic participation to find a sustainable solution to overcome this critical time. The COP26, the UN climate conference, which took place last year in Glasgow, has the highest participation rate in COP´s history despite the global pandemic. The world was expecting more ambitious actions for a clean global energy transition to achieve the 1.5 degree-goal. It is now clear that this ambitious goal cannot be achieved only by political decisions. A strong civic participation is required to make sure that the global warming will not lead to an irreversible status of the climatic crisis characterized by climate events, which will make the life of human beings not more sustainable on this planet. Social innovations are the key to overcome this crisis and provide a sustainable solution to the mitigation of global warming towards the achievement of 1.5 degree-goal. Social innovations are defined as “New ideas (products, services and models) that simultaneously meet social needs (more effectively than alternatives) and create new social relationships or collaborations. In other words, they are innovations that are not only good for society but also enhance society’s capacity to act”. Source: Empowering people, driving change, Bureau of European Advisers (BEPA), Brussels (2011). In the renewable energy sector, social innovations are identified as the business models able to support the production of renewable energy and, at the same time, the cooperation among citizens. As common denominator they have the concept of “power of many” to highlight that, through the union of small contributions, it is possible to build projects having positive environmental, economic and social impacts. The business models implementing social innovation in the renewable energy sector are cooperatives, aggregators and crowdfunding platforms. The development of renewable energies and a greater civic participation will be the two pillars of the clean energy transition. Social innovations can combine these two fundamental aspects and lead to the energy democracy and, as consequence, to a mitigation of the global warming. This paper has been prepared in the framework of the European project SocialRES (Fig. 1), which has the aim to investigate the business models of social innovations in the renewable energy sector to provide the owners or managers of crowdfunding platforms and cooperatives and aggregators, named “the facilitators of energy democracy”, with new tools to further support the production of renewable energy and the participation of citizens.

In this paper, one presents some results concerning the behavior of the total cross section and $ρ$-parameter at asymptotic energies in proton-proton ($pp$) and antiproton-proton ($\bar{p}p$) collisions. For this intent, we consider three of the main theoretical results in high energy physics: the crossing property, the derivative dispersion relation, and the optical theorem. The use of such machinery allows the analytic formulas for wide set of the measured global scattering parameters and some important relations between them. The suggested parameterizations approximate simultaneously the energy dependence for total cross section and $ρ$-parameter for $pp$ and $\bar{p}p$ with statistically acceptable quality in multi-TeV region. Also the qualitative description is obtained for important interrelations, namely difference, sum and ratio of the antiparticle-particle and particle-particle total cross sections. Despite the reduced number of experimental data for the total cross section and $ρ$-parameter in TeV-scale, which turns any prediction for the beginning of the asymptotic domain a hard task, the fitting procedures indicates that asymptotia lies in the energy range 25.5-130 TeV. Moreover, in the asymptotic regime, one obtains $α_{\mathbb{P}}=1$. Detailed quantitative study of energy behavior of measured scattering parameters and their combinations in ultra-high energy domain indicates that the scenario with the generalized formulation of the Pomeranchuk theorem is more favorable with respect to the original formulation of this theorem., 22 pages, 5 figures and 7 tables

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

The SWGO Collaboration is in the process of designing and prototyping a wide field of view, high duty cycle complement to CTA and the existing ground-based particle detectors of the Northern Hemisphere (HAWC and LHAASO). In this contribution, we will compare the various technological options for designing the detector and present an overarching system design accommodating them. We will introduce a feasible reference configuration that is used for the first large-scale simulations and cost estimates, and show ongoing prototyping work focused on reaching a maintenance-free and cost-effective detector.

The Southern Wide-field Gamma-ray Observatory (SWGO) will use the well-established and cost-effective technique of detecting Cherenkov light produced in water-filled detection units for TeV gamma-ray astronomy. Leveraging detector material reflectivity together with an optimised aspect ratio is an option to improve the performance of an array of such detector units. The double-layered Water Cherenkov Detector units comprise chambers with single photosensors in each. A reflective upper compartment enhances sensitivity to impinging secondary particles. A shallow lower compartment enables muon tagging and consequently improves the gamma hadron separation power of the observatory. Here we present detailed studies on the double-layered unit design.

BackgroundIn the search for active drugs against COVID-19, the indications of many have been redirected. Ivermectin and Hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers.ObjectivesThis clinical trial analyzes the efficacy of Ivermectin and Hydroxychloroquine in patients with moderate COVID-19 and in need of hospitalization.MethodsThis a controlled, clinical, randomized, double-blind trial that included patients with COVID-19-induced pneumonia and hospitalization criteria, but no severe respiratory failure. Patients were randomized to one of three groups: Group1-hydroxychloroquine, 400 mg every 12 hours on the first day and subsequently, 200 mg every 12 hours for 4 days, Group 2-ivermectin, 12 mg or 18 mg, according to patient weight and, Group 3-placebo. At inclusion, blood samples for arterial blood gases and biochemical markers associated with a poor prognosis were obtained. The primary outcome was established as the duration of hospitalization until discharge due to patient improvement, the total duration of hospitalization, and the safety outcomes were either respiratory deterioration or death.ResultsDuring the month of August, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs. (±16.9) were included, with a greater proportion of males (n=66, 62.2 %). Seventy-two percent (72%) (n= 76) had an associated comorbidity. Ninety percent (90 %) of patients were discharged due to improvement (n=96). The average duration of hospitalization was 6 days (IQR, 3 – 10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs Group 2: 6 vs Group 3: 5, p=0.43) nor in respiratory deterioration or death (Group 1: 18 % vs Group 2: 22.2 % vs Group 3: 24.3 %, p =0.83).ConclusionsIn non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.ClinicalTrials identifier NCT04391127

Vascular malformations (VM) are congenital, benign, and relatively frequent lesions. Scant data have been published about the epidemiology, clinical presentation, and treatment of VM from a dermatologist's perspective. The substantial differences between subtypes, broad range of specialists consulted and confusing nomenclature used over previous years may hamper a correct diagnosis. The main objective of this study is to describe VM epidemiology. As a secondary endpoint we evaluate clinical characteristics, clinical-radiological correlation and treatment approaches. We carried out an observational, descriptive, retrospective study. Cases presented to the multidisciplinary committee of our hospital from 2009 to 2019 were retrieved. Electronic medical records, monthly committee reports and the iconographic archive were reviewed and statistically analyzed. Overall, venous malformations (VeM) are the most frequent VM, followed by capillary malformations (CM), arterioVeM and lymphatic malformations (LM). Considering only patients under 16, CMs are the most frequent ones. Capillary and LMs are larger than venous or arteriovenous. While CMs are usually asymptomatic, symptomatic cases are threefold more frequent in the other subtypes. Decisions on active or conservative management depend on VM size but not location or patient age. CMs are mainly treated with laser therapy; venous with sclerotherapy or surgery; arteriovenous with surgery and lymphatic with surgery or sirolimus. Dermatologists play an important role in VM diagnosis and management. Our 10-year multidisciplinary experience should contribute to the literature and represent a practical resource for clinicians and researchers.

Treatment of ß-lactamase positive bacterial infections with a combination of amoxicillin (AMOX) and clavulanic acid (CLAV) causes idiosyncratic drug-induced liver injury (iDILI) in a relevant number of patients, often with features of intrahepatic cholestasis. This study aims to determine serum bile acid (BA) levels in amoxicillin/clavulanate (A+C)-iDILI patients and to investigate the mechanism of cholestasis by A+C in human in vitro hepatic models. In six A+C-iDILI patients, significant elevations of serum primary conjugated BA definitely demonstrated A+C-induced cholestasis. In cultured human Upcyte hepatocytes and HepG2 cells, CLAV was more cytotoxic than AMOX, and, at subcytotoxic concentrations, it altered the expression of more than 1,300 genes. CLAV, but not AMOX, downregulated the expression of key genes for BA transport (BSEP, NTCP, OSTa and MDR2) and synthesis (CYP7A1 and CYP8B1). CLAV also caused early oxidative stress, with reduced GSH/GSSG ratio, along with induction of antioxidant nuclear factor erythroid 2-related factor 2 (NRF2) target genes. Activation of NRF2 by sulforaphane also resulted in downregulation of NTCP, OSTa, ABCG5, CYP7A1 and CYP8B1. CLAV also inhibited the BA-sensor farnesoid X receptor (FXR), in agreement with the downregulation of FXR targets BSEP, OSTa and ABCG5. We conclude that CLAV, the culprit molecule in A+C, downregulates several key biliary transporters by modulating NRF2 and FXR signaling, thus likely promoting intrahepatic cholestasis. On top of that, increased ROS production and GSH depletion may aggravate the cholestatic injury by A+C.

In this work, the distance between a quark-antiquark pair is analyzed through both the confinement potential as well as the hadronic total cross section. Using the Helmholtz free energy, entropy is calculated near the minimum of the total cross section through the confinement potential. A fitting procedure for the proton-proton total cross section is performed, defining the fitting parameters. Therefore, the only free parameter remaining in the model is the mass scale $\kappa$ used to define the running coupling constant of the light-front approach to QCD. The mass scale controls the distance $r$ between the quark-antiquark pair and, under some conditions, it allows the occurrence of free quarks even in the confinement regime of QCD., Comment: 16 pages, 2 figures. This improved version contains corrections for some typos as well as some development in discussions along the text

Gut microbiota plays a key role in obesity and non-alcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. We aim to evaluate a nutritional intervention together with the administration of the bacteria Akkermansia muciniphila and the antioxidant quercetin in an in vivo model of early obesity and NAFLD. 21-day-old rats were fed with control or high-fat diet for six weeks. Then, all animals received control diet supplemented with/without quercetin and/or A. muciniphila for three weeks. Gut microbiota, NAFLD-related parameters, circulating bile acids (BAs) and liver gene expression were analyzed. The colonization with A. muciniphila was associated with less body fat, while synbiotic treatment caused a steatosis remission, linked to hepatic lipogenesis modulation. The synbiotic promoted higher abundance of Cyanobacteria and Oscillospira, and lower levels of Actinobacteria, Lactococcus, Lactobacillus and Roseburia. Moreover, it favored elevated unconjugated hydrophilic BAs plasma levels and enhanced hepatic expression of BA synthesis and transport genes. A. muciniphila correlated with circulating BAs and liver lipid and BA metabolism genes, suggesting a role of this bacterium in BA signaling. Beneficial effects of A. muciniphila and quercetin combination are driven by gut microbiota modulation, the shift in BAs and the gut-liver bile flow enhancement.

Background: Although no specific treatment for COVID 19 has been proven effective yet, some drugs with in vitro potential against SARS-CoV-2 virus have been proposed for clinical use. Hydroxychloroquine has in vitro anti-viral and immunomodulatory activity, but there is no current clinical evidence of its effectiveness on the outcome of the disease. Methods: We enrolled all 18-85 years old inpatients from Central Defense Hospital, Madrid, Spain, who were hospitalised due to COVID-19 and had a definitive outcome (either dead or discharged). We used a statistical survival analysis. Results: We analysed 220 medical records. 166 patients met the inclusion criteria. 48,8 % of patients not treated with HCQ died, versus 22% in the group of hydroxychloroquine (p=0,002). According to clinical picture at admission, hydroxychloroquine increased the mean cumulative survival in all groups from 1,4 to 1,8 times. This difference was statistically significant in the mild group. Conclusions: in a cohort of 166 patients between 18 to 85 years hospitalised with COVID-19, hydroxychloroquine treatment with an initial loading dose of 800mg improved patient survival when admitted in early stages of the disease. There was a non-statistically significant trend towards survival in all groups, which will need to be clarified in subsequent studies.

PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation. (C) 2019 by American Society of Clinical Oncology

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation. (C) 2019 by American Society of Clinical Oncology

Objective: To identify the prevalence of musculoskeletal disorders in adolescents, and to analyze this prevalence relationship with sociodemographic, anthropometric and contextual variables. Methods: An observational, cross-sectional, descriptive/relational study with quantitative approach was conceptualized, involving 632 adolescents with mean age of 13.36 from six school groups from Central and North Portugal. Data collection protocol included questions of sociodemographic, anthropometric and contextual nature, and also the “Nordic Musculoskeletal Questionnaire” to assess musculoskeletal disorders. Results: Data showed that 47.4% of adolescents mentioned musculoskeletal disorders within the last 3 months, located in the shoulders (27.8%), dorsal region (25.3%), thigh/hips (26.1%), neck (23.4%), lumbar region (22.8%), and knees (19.6%). We found that musculoskeletal disorders are more prevalent in female adolescents, and among those who spend longer time watching television per day, and also those who go to school by foot or bicycle. Conclusion: The prevalence of musculoskeletal disorders in adolescents is high and has multicausal origin, turning imperative the implementation of preventive and readapted actions to promote a better musculoskeletal function. Objetivo: Identifi car a prevalência das perturbações músculo-esqueléticas em adolescentes e analisar a sua relação com variáveis sociodemográfi cas, antropométricas e contextuais. Métodos: Conceptualizou-se um estudo observacional, transversal, descritivo/relacional de cariz quantitativo, que envolveu 632 adolescentes de seis agrupamentos de escolas das zonas centro e norte de Portugal, com média de idades de 13,36 anos. O protocolo de colheita de dados integrava questões de cariz sociodemográfi co, antropométrico, contextual e ainda o “Questionário Nórdico Músculo-Esquelético” para avaliar as perturbações músculo-esqueléticas. Resultados: Os dados mostraram que 47,4% dos adolescentes referem perturbação músculo-esqueléticas nos últimos 3 meses, localizando-se estas aos níveis dos ombros (27,8%), região dorsal (25,3%), coxa/anca (26,1%), pescoço (23,4%), zona lombar (22,8%) e joelhos (19,6%). Verifi cou-se ainda, que as perturbações músculo-esqueléticas são mais prevalentes nos adolescentes do género feminino, naqueles que gastam mais tempo por dia a ver televisão e ainda nos que se deslocam para a escola a pé ou de bicicleta. Conclusão: A prevalência das perturbações músculo-esqueléticas nos adolescentes é elevada, tem origem multicausal, tornando-se imperativa a implementação de intervenções de prevenção e readaptação promotoras de um funcionamento músculo-esquelético otimizado. info:eu-repo/semantics/publishedVersion

Background Monitoring seasonal influenza epidemics is the corner stone to epidemiological surveillance of acute respiratory virus infections worldwide. This work aims to compare two sentinel surveillance systems within the Daily Acute Respiratory Infection Information System of Catalonia (PIDIRAC), the primary care ILI and Influenza confirmed samples from primary care (PIDIRAC-ILI and PIDIRAC-FLU) and the severe hospitalized laboratory confirmed influenza system (SHLCI), in regard to how they behave in the forecasting of epidemic onset and severity allowing for healthcare preparedness. Methods Epidemiological study carried out during seven influenza seasons (2010-2017) in Catalonia, with data from influenza sentinel surveillance of primary care physicians reporting ILI along with laboratory confirmation of influenza from systematic sampling of ILI cases and 12 hospitals that provided data on severe hospitalized cases with laboratory-confirmed influenza (SHLCI-FLU). Epidemic thresholds for ILI and SHLCI-FLU (overall) as well as influenza A (SHLCI-FLUA) and influenza B (SHLCI-FLUB) incidence rates were assessed by the Moving Epidemics Method. Results Epidemic thresholds for primary care sentinel surveillance influenza-like illness (PIDIRAC-ILI) incidence rates ranged from 83.65 to 503.92 per 100.000 h. Paired incidence rate curves for SHLCI -FLU / PIDIRAC-ILI and SHLCI-FLUA/ PIDIRAC-FLUA showed best correlation index' (0.805 and 0.724 respectively). Assessing delay in reaching epidemic level, PIDIRAC-ILI source forecasts an average of 1.6 weeks before the rest of sources paired. Differences are higher when SHLCI cases are paired to PIDIRAC-ILI and PIDIRAC-FLUB although statistical significance was observed only for SHLCI-FLU/PIDIRAC-ILI (p-value Wilcoxon test = 0.039). Conclusions The combined ILI and confirmed influenza from primary care along with the severe hospitalized laboratory confirmed influenza data from PIDIRAC sentinel surveillance system provides timely and accurate syndromic and virological surveillance of influenza from the community level to hospitalization of severe cases.

Gut microbiota contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis by multiple mechanisms not yet completely understood. Novel differential features between germ-free mice (GFm) transplanted with protective or non-protective cecal microbiota against NAFLD are investigated.

Scope Modulation of intestinal microbiota has emerged as a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by quercetin and intestinal microbiota transplantation can influence NAFLD development. Methods and results Gut microbiota donor mice are selected according to their response to high-fat diet (HFD) and quercetin in terms of obesity and NAFLD-related biomarkers. Germ-free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers. Gut microbiota from the HFD-responder donor predisposed transplanted germ-free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity-associated NAFLD development. Conclusions The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity-related NAFLD.

Splenogonadal fusion, a rare cause of pediatric testicular mass. Clinical case The splenogonadal fusion is a rare anatomical variation, with only a few reports in the literature. The close re-lationship between the spleen and the primitive left gonad in a specific moment of the embryonic development could explain this phenomenon. Objective: To point out the clinical presentation and treatment of this condi-tion, through the first case published in our country. Clinical case: We report the case of a male child, 2 years 10-month-old, who consulted for silent swelling of the left testis, which Doppler ultrasound study revealed a hypervascular, polar mass. A surgical exploration was performed, and a solid, adherent, liver-like structure was observed over the testicle. The intraoperatory biopsy was informed as benign splenic tissue. Conclusion: The reviewed articles describe important information about the development, classification, presentation and ma-nagement of this condition. The knowledge and inclusion of this condition in the differential diagnosis of pediatric testicular masses allows the medical team to choose for conservative therapeutic measures. Once the diagnosis is established, often intraoperatively, a complete resection of the splenic tissue is enough for these patients, avoiding an unnecessary orchiectomy. (Key words: Splenogonadal fusion, testis, spleen, testicular mass).Rev Chil Pediatr 2013; 84 (3): 308-312RESUMENLa fusion esplenogonadal es una variacion anatomica infrecuente, con un pequeno numero de reportes en la literatura. La estrecha relacion entre el bazo y la gonada primitiva izquierda en un momento del desarrollo em-brionario logra explicar la existencia de este fenomeno. Objetivo: Comunicar el primer reporte en la literatura nacional de fusion esplenogonadal. Caso clinico: Preescolar de 2 anos 10 meses que consulto por aumento de volumen silente en testiculo izquierdo estudiado mediante ecografia, la cual revelo una masa hipervascular en su polo superior. Se decidio su exploracion quirurgica donde se aprecio una estructura solida, bien adherida

Background & Aims: The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. Methods: The expression of liver VDR was investigated in apolipoprotein E knockout (apoE(-/-)) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE(-/-) mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR transfection or silencing. The role of VDR in fibrosis was also determined in VDR knockout mice (VDR-/-) treated with thioacetamide. Results: Expression of liver VDR was markedly induced in two mouse models of NAFLD, as well as in patients with hepatosteatosis, but decreased in non-alcoholic steatohepatitis. VDR deletion in high fat diet-fed apoE(-/-) mice protected against fatty liver, dyslipidemia and insulin resistance, and caused a decrease in taurine-conjugated bile acids, but did not influence fibrosis by thioacetamide. apoE(-/-)VDR(-/-) mouse livers showed decreased gene expression of CD36, DGAT2, C/EBP alpha and FGF21, and increased expression of PNPLA2, LIPINI and PGC1 alpha. Treatment of apoE(-/-) mice on high fat diet with paricalcitol had modest opposite effects on steatosis and gene expression. Finally, this set of genes showed concordant responses when VDR was overexpressed or silenced in HepG2 cells. Conclusions: Induced hepatocyte VDR in NAFLD regulates key hepatic lipid metabolism genes and promotes high fat diet-associated liver steatosis. Therapeutic inhibition of liver VDR may reverse steatosis in early NAFLD. Lay summary: The amount of vitamin D receptor is induced early in the livers of mice and humans when they develop nonalcoholic fatty liver disease. If the gene for the vitamin D receptor is deleted, hepatic lipid metabolism changes and mice do not accumulate fat in the liver. We conclude that the vitamin D receptor can contribute to the fatty liver disease promoted by a high fat diet. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Transverse testicular ectopia (TTE) is a rare congenital anomaly in which both testes descend through the same inguinal canal. The most frequent clinical presentation is undescended testis (UDT) with ipsilateral inguinal hernia and contralateral non-palpable testis. This condition is often diagnosed during surgery and is frequently associated with other anomalies. There is controversy in the surgical management of TTE. Considerations for TTE repair include avoiding damage to the testes or vas deferens and detection of other congenital anomalies. Frequently, the vas deferens and testicular tissues are joined, and dissection of these structures can cause damage. In this article, we report four patients with TTE, describe the surgical approach made in each case, and provide a review of the literature.

The small heterodimer partner (SHP) (NR0B2) is an atypical nuclear receptor that lacks a DNA-binding domain. It interacts with and inhibits many transcription factors, affecting key metabolic processes, including bile acid, cholesterol, fatty acid, and drug metabolism. Our aim was to determine the influence of steatotic drugs and nonalcoholic fatty liver disease (NAFLD) on SHP expression and investigate the potential mechanisms. SHP was found to be repressed by steatotic drugs (valproate, doxycycline, tetracycline, and cyclosporin A) in cultured hepatic cells and the livers of different animal models of NAFLD: iatrogenic (tetracycline-treated rats), genetic (glycine N-methyltransferase-deficient mice), and nutritional (mice fed a methionine- and choline-deficient diet). Among the different transcription factors investigated, CCAAT-enhancer-binding protein alpha (C/EBP alpha) showed the strongest dominant-repressive effect on SHP expression in HepG2 and human hepatocytes. Reporter assays revealed that the inhibitory effect of C/EBP alpha and steatotic drugs colocalize between -340 and -509 base pair of the SHP promoter, and mutation of a predicted C/EBP alpha response element at -473 base pair abolished SHP repression by both C/EBP alpha and drugs. Moreover, inhibition of major stress signaling pathways demonstrated that the mitogen-activated protein kinase kinase 1/2 pathway activates, while the phosphatidylinositol 3 kinase pathway represses SHP in a C/EBP-dependent manner. We conclude that SHP is down-regulated by several steatotic drugs and in advanced NAFLD. These conditions can activate signals that target C/EBP alpha and consequently repress SHP, thus favoring the progression and severity of NAFLD.

Scope: Flavonoids and related compounds seem to have favorable effects on nonalcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3-kinase (PI3K)/AKT pathway modulation. Methods and results: We used an in vivo model based on methionine-and choline-deficient (MCD) diet-fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD-fed mice showed classical pathophysiological characteristics of nonalcoholic steatohepatitis, associated with altered transcriptional regulation of fatty acid uptake-and trafficking-related gene expression, with increased lipoperoxidation. PI3K/AKT pathway was activated by MCD and triggered gene deregulation causing either activation or inhibition of all studied genes as demonstrated through cell incubation with the PI3K-inhibitor LY294002. Treatment with quercetin reduced AKT phosphorylation, and oxidative/nitrosative stress, inflammation and lipid metabolism-related genes displayed a tendency to normalize in both in vivo and in vitro models. Conclusion: These results place quercetin as a potential therapeutic strategy for preventing NAFLD progression by attenuating gene expression deregulation, at least in part through PI3K/AKT pathway inactivation.

BACKGROUND: Accuracy of MRI in assessing mesorectal fascia and predicting circumferential resection margin decreases in low anterior rectal tumors. OBJECTIVE: The purpose of this work was to evaluate the accuracy of endorectal ultrasound in predicting the pathologic circumferential resection margin in low rectal anterior tumors and to compare it with MRI findings. DESIGN: This was a prospective series comparing the preoperative circumferential resection margin assessed by endorectal ultrasound and MRI with pathologic examination. SETTINGS: The study was conducted by a specialized colorectal multidisciplinary team at a tertiary teaching hospital. PATIENTS: Between 2002 and 2008, 76 patients with mid to low rectal cancer were preoperatively evaluated by endorectal ultrasound and MRI and underwent total mesorectal excision without neoadjuvant radiochemotherapy. Twenty-seven patients with posterior or postero-lateral tumors were excluded, leaving 49 patients with anterior or antero-lateral tumors for the present subanalysis. We compared preoperative circumferential resection margin status using endorectal ultrasound and MRI with pathologic examination. INTERVENTIONS: We conducted a comparison between preoperative circumferential resection margin status and pathologic examination after total mesorectal excision surgery. MAIN OUTCOME MEASURES: Accuracy in predicting pathologic circumferential resection margin status was measured. RESULTS: Overall accuracy of endorectal ultrasound and MRI in assessing circumferential resection margin status was 83.7% and 91.8%, with negative predictive values of 97.2% and 97.5%. When focusing on low rectal tumors, the overall accuracy of endorectal ultrasound increased to 87.5%, whereas the accuracy of MRI decreased to 87.5%, with a negative predictive value of 95.6% for both diagnostic tests. LIMITATIONS: The sample size is small, and interobserver variability in radiologic assessment was not evaluated. CONCLUSIONS: Endorectal ultrasound can help MRI in predicting circumferential resection margin involvement in mid to low anterior rectal cancer, especially at the low third of the rectum, with a high negative predictive value.

There is experimental evidence that some antioxidant flavonoids show therapeutic potential in the treatment of hepatitis C through inhibition of hepatitis C virus (HCV) replication. We examined the effect of treatment with the flavonols quercetin and kaempferol, the flavanone taxifolin and the flavone apigenin on HCV replication efficiency in an in vitro model. While all flavonoids studied were able to reduce viral replication at very low concentrations (ranging from 0.1 to 5 mu M), quercetin appeared to be the most effective inhibitor of HCV replication, showing a marked anti-HCV activity in replicon-containing cells when combined with interferon (IFN)alpha. The contribution of oxidative/nitrosative stress and lipogenesis modulation to inhibition of HCV replication by quercetin was also examined. As expected, quercetin decreased HCV-induced reactive oxygen and nitrogen species (ROS/RNS) generation and lipoperoxidation in replicating cells. Quercetin also inhibited liver X receptor (LXR)alpha-induced lipid accumulation in LXR alpha-overexpressing and replicon-containing Huh7 cells. The mechanism underlying the LXR alpha-dependent lipogenesis modulatory effect of quercetin in HCV-replicating cells seems to involve phosphatidylinositol 3-kinase (PI3K)/AKT pathway inactivation. Thus, inhibition of the PI3K pathway by LY294002 attenuated LXR alpha upregulation and HCV replication mediated by lipid accumulation, showing an additive effect when combined with quercetin. Inactivation of the PI3K pathway by quercetin may contribute to the repression of LXR alpha-dependent lipogenesis and to the inhibition of viral replication induced by the flavonol. Combined, our data suggest that oxidative/nitrosative stress blockage and subsequent modulation of PI3K-LXR alpha-mediated lipogenesis might contribute to the inhibitory effect of quercetin on HCV replication.

Liver fatty acid binding protein (FABP1) prevents lipotoxicity of free fatty acids and regulates fatty acid trafficking and partition. Our objective is to investigate the transcription factors controlling the human FABP1 gene and their regulation in nonalcoholic fatty liver disease (NAFLD). Adenovirus-mediated expression of multiple transcription factors in HepG2 cells and cultured human hepatocytes demonstrated that FOXA1 and PPARa are among the most effective activators of human FABP1, whereas C/EBPa is a major dominant repressor. Moreover, FOXA1 and PPARa induced re-distribution of FABP1 protein and increased cytoplasmic expression. Reporter assays demonstrated that the major basal activity of the human FABP1 promoter locates between -96 and -229bp, where C/EBPa binds to a composite DR1-C/EBP element. Mutation of this element at -123bp diminished basal reporter activity, abolished repression by C/EBPa and reduced transactivation by HNF4a. Moreover, HNF4a gene silencing by shRNA in HepG2 cells caused a significant down-regulation of FABP1 mRNA expression. FOXA1 activated the FABP1 promoter through binding to a cluster of elements between -229 and -592bp, whereas PPARa operated through a conserved proximal element at -59bp. Finally, FABP1, FOXA1 and PPARa were concomitantly repressed in animal models of NAFLD and in human nonalcoholic fatty livers, whereas C/EBPa was induced or did not change. We conclude that human FABP1 has a complex mechanism of regulation where C/EBPa displaces HNF4a and hampers activation by FOXA1 and PPARa. Alteration of expression of these transcription factors in NAFLD leads to FABP1 gen repression and could exacerbate lipotoxicity and disease progression.

Douglas Wong proposed a new classification of tumor penetration in the rectal wall (T stage) in an attempt to incorporate the prognostic heterogeneity of T3 rectal cancers into the preoperative staging.

espanolCaso clinico: Se presenta el caso de un varon de 58 anos que acudio a urgencias con dolor ocular y perdida progresiva de vision del ojo izquierdo. La exploracion oftalmologica detecto una masa pigmentada en el angulo iridocorneal afectando cuerpo ciliar. El paciente presentaba glaucoma secundario a la lesion melanica. La oftalmoscopia mostro una tumoracion coroidea pigmentada de gran tamano. Tras la enucleacion ocular, el estudio anatomopatologico confirmo el diagnostico de melanoma ocular difuso. Discusion: El melanoma uveal difuso es un tumor maligno que produce metastasis en los primeros anos tras su diagnostico, siendo la enucleacion el tratamiento indicado. EnglishCase report: We report the case of a 58-year-old man who presented at our emergency department with ocular pain and progressive loss of vision in his left eye. Ophthalmic examination detected a pigmented mass in the iridocorneal angle, involving the ciliary body. Glaucoma had also developed secondary to the melanotic lesion. Ophthalmoscopy showed a large pigmented choroidal tumor. After enucleation, pathologic examination confirmed the diagnosis of a diffuse ocular melanoma. Discussion: Diffuse uveal melanoma is a malignant tumor that metastasises early. Enucleation is the treatment of choice.

La deficiencia de hierro es la carencia nutricional más frecuente y la principal causa de anemia en el niño. En un estudio a escala nacional (1974-1975) la prevalencia de anemia en preescolares fue de 18,8%. Para evaluar la nutrición de hierro, se seleccionaron 96 niños sanos (2 a 5 años) de la comuna La Pintana. Previo consentimiento informado, se obtuvo una muestra de sangre para medir hemoglobina, volumen corpuscular medio, protoporfirina libre eritrocitaria y ferritina sérica. Ninguno de los niños presentó anemia ferropriva o eritropoyesis deficiente en hierro. Sólo un 5,2% de los sujetos tenía una depleción de los depósitos de hierro. 99% y 69% de los niños consumían diariamente pan y leche fortificada (Leche Purita Cereal). Es altamente probable que la mejoría de la nutrición de hierro de los niños se deba al consumo de alimentos fortificados con hierro: harina de trigo y la Leche Purita Cereal distribuida por el Programa Nacional de Alimentación Complementaria Iron deficiency is the single most common nutritional disorders worldwide and the main cause of anemia in infancy and childhood. The prevalence of anemia in a Chilean national sample of preschool children was 18.8% (1974-1975). Ninety-six healthy children aged 2 to 5 years from La Platina were selected to evaluate iron nutritional status. After informed written consent was obtained from the parents, a venous sample was drawn to measure hemoglobin, mean corpuscular volume, free erythrocyte protoporhyrin and serum ferritin. None of the children presented iron deficiency anemia or iron-deficient erythropoiesis, and only 5.2% of the subjects had iron depleted stores. Ninety-nine and 69% of the children consumed daily bread and iron fortified milk (Leche Purita Cereal), respectively. It is highly likely that the iron fortification of wheat flour and the milk distributed by the National Complementary Food Program has improved iron nutrition status of children

From march 1992 to february 1993, the Ministry of Health of Chile sponsored a program intended to improve medical core and gather epidemiologic information on urinary trcct infections in the pediatric population served by the Northern Sarriago Metropolitan Health Service |SSMM}. During this period, suspicious cases of urinary tract infections (UTI) presenting at seven lout or 14] ambulatory care centers and at the local pediatric hospital emergency room were refered to a special unit [U I clinic] ot that same hospital, where diagnoses were confirmed and patients were treated and followed by a standard protocol, including renal ultrasonogram and voiding cystourefhrography to all patients without previous radiologic evaluation. By the time of this study the SSMN cared for 188 329 children [age under 15 years), 108 221 of 'hem were adscribed to the participating health centers, and 1 .275 patients were referred to the UTI clinic, 630 being confi'rned UTI cases. The attack rate of the disease was significantly higher in the participating healtn centers [3-7/1.000), thar, /n the non participating ones (2.7/1 .000, p < 0.0003). Acute pyelonephritis was significantly more ccnmon in children under 24 months of age then among other ages: OR=3.3 [IC95%-2.1-5.3); p < 0.0000001. E. co'ii was the predorrvnant bacterial pathogen in males and females, but identification of non E. coll bacteriae was significantly more frequent among male patients (OR - 17,3; (1C 95% = 8.0 - 38.0). Five hundred and twenty two children were followed beyond recover/ of the index UTI and 148 had at least a second episode of UTI during the fo.low-jp period [1 to 18 months, median and mode 6 months); 87,8% of the detected recurrences occurred before the seventh month of follow-up. Age 24 to 71 months and non E. coll infections were associated with significan-ly higher risk of recurrences: OR = 2.5; (1C 95% - 1.5-4.0) and OR - 2,5 (!C 95% = 1,2-5,2), respectively. Male parents and those with acute pyelonephitis were at significantly higher risk of bearing morphologic abnormalities: OR = 2,0; (1C 95% = 1,03-3,9), and OR = 2,0; (1C 95% = 1,2-3,5).

The effect of atrazine inthe populstions dynamics of soil microorgsnism in Saldana, Tolima was evaluated. The soil microorganism studied were bacteria in general, phosphatesolubilizing bacteria, desnitrificant, aminificants, nitrobacte and nitrosomonas. We used a completely randomnized design with five treatments and four repetitions. Results were analyzed using Analysis of variance Treatments consisted of (1) original soil, (2) sterilized soil, (3) soil with substrate of corn stubble, (4) soil treated with 1.5 kg i.a. atrazine/ha, (5) soil with substrate of corn stubble and atrazine. The null hypothesis has consisted that there are not significant differences between population. Differences in variance were compared to F distribution of 5% significance level. The Turkey's test was also used, with the same significance level. Results showed that, as time goes on, the atrazine herbicide has a detrimental effect on the amonificant bacteria populations, as well as on nitrosomonas, desnitrificant and nitrobacter populations. However , ther corn stubble substrate with atrazine has reduced the effect by increasing the number of colony-forming units per gram of soil (U.F.C./g of soil).

Objective: This study evaluates the vectorcardiographic criteria for left ventricular hypertrophy (LVH) in patients with essential hypertension. It also simultaneously assesses the acuracy of the VCG against the most used ECG criteria in the clinical setting. Methods: From the hypertension unit of the Cardiology Division of Sao Paulo Federal University 60 consecutive patients were selected (43 women and 16 men with average age of 49 * 9.4y) with diagnosis of essential hypertension. The patients were submitted to the ECG and VCG examinations on the same day and to the M-mode echocardiogram (Echo) examination around 2 weeks. We assessed the following electrocardiographic criteria to LVH: Sokolow-Lyon voltage (sum of amplitude of the S wave on lead V1 and R wave on lead V5 or V6 * 3.5 mV; Romhilt-Estes point score with partition values of * 5 points; gender-specific Cornell voltage (S V3 + R aVL [gt ] 2.8 mV in men and [gt ] 2.0 mV in women) and Peruggia score that requires the presence at least one of the following criteria: S V3 + R aVL [gt ] 2.4 mV in men or 2.0 mV in women; left ventricular strain or Romhilt-Estes score of 5 points or more. The VCG tracings were recorded with the Hewlett Packard model 1520A with the Frank system for electrode placement. The LVH diagnosis was met when the maximum QRS vector was directed to the left and posteriorly in the transverse and to the left and inferiorly in the frontal planes with the magnitude exceeding 2 mV. The results of the Echo was taken as golden standard and LVH was determined according to the recommendation of the ASE. The cut-off value to presence of LVH was 120 and 150 mg/m2 to women and men, respectively. All examination tracings were interpreted by 3 investigators without knwoledge of other patient data. Results: Comparative Analysis Considering the Echocardiogram as Golden Standard Conclusion: The VCG was much more sensitive than any current ECG criteria. The agreement analysis showed that the VCG, with simple and practical criteria, can be an operational alternative to a reliable diagnosis of LVH in populations with essential hypertension.

The Southern Wide-view Gamma-ray Observatory (SWGO) will be a next-generation gamma-ray observatory using a large array of particle detectors at a high elevation site in South America. This project is currently in a three years R & D phase in which the design will be optimised for cost and performance. Therefore it is crucial to efficiently evaluate the impact of different design options on the scientific objectives of the observatory. In this contribution, we will introduce the strategy and the simulation framework in which this evaluation takes place.

The Southern Wide-field Gamma-ray Observatory (SWGO) is the next-generation gamma-ray observatory, currently in an R\&D phase. The experiment is expected to have a large array of water Cherenkov detectors (WCD) placed at a high elevation (> 4.4 km a.s.l.) in South America. Here we present a WCD concept with reduced surface area and height of stations comprising four PMTs at the bottom. We show that it is possible to reach an excellent gamma/hadron discrimination by analysing the data gathered by this station with machine learning techniques. Such performance can be achieved by analysing the shower patterns at the ground or through the PMTs signal time structure to tag muons. Moreover, it is shown that the station's performance does not depend on the array configuration (dense or sparse) nor on the shower inclination ($\theta < 40^\circ$). Such a concept reduces the cost associated with the transport of massive amounts of water to high elevation sites while keeping a high physics performance. Therefore, it could be a good candidate station for SWGO, enabling to reach good sensitivities from low energies ($\sim 100\,$GeV) up to the PeV region, covering large ground surface areas (few square km).