Search

O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

Introduction: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. Methods and Analysis: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494

Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines.

ObjectivesIn this study, we aimed to systematically review the literature of the prevalence of systemic antibacterial use during pregnancy and to perform a descriptive analysis focused on methodological characteristics.Materials and methodsThis study was registered in PROSPERO under protocol number CRD42022376634. Medline, Embase, Scientific Electronic Library Online, Biblioteca Virtual em Saúde, Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases were searched (published studies until November 3rd, 2022). Selected studies were population-based cross-sectional or cohort, carried out with pregnant women, and providing information about the prevalence of systemic antibacterial use at least in one trimester of pregnancy. Reviewers conducted in pairs the title and abstract screening, eligibility criteria check, and data extraction of selected studies. Quality appraisal was performed with an adapted version of the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Data of included studies were pooled into a graphical and tabular summary.ResultsA total of 16,251,280 pregnant women and 5,169,959 pregnancy registers were identified. The prevalence estimates of systemic antibacterial use during pregnancy ranged from 2.0% (95%CI 2.0-2.0) to 64.3% (95%CI not reported) in the 79 included studies. The majority were performed in high-income countries (91.5%). Overall, the studies revealed considerable prevalence heterogeneity in terms of study type and dataset used. The 95% confidence intervals were not reported in 41% of studies.ConclusionThe disparities in the prevalence of systemic antibacterial use during pregnancy can be related to methodological issues and different health policies. Lack of uniform databases and changes in data collection methods over time should be taken into account in public health strategy planning. The scarce evidence in low- and middle-income settings hampers the comprehensiveness of the global prevalence of antibacterial use during pregnancy.

Introduction Nearly 30 000 Mexican women develop breast cancer annually, frequently presenting unmet supportive care needs. In high-income countries, incorporating electronic patient-reported outcomes (ePROs) into cancer care has demonstrated potential for increasing patient-centred care and reducing unmet needs. No such ePRO interventions have been implemented in Mexico. This paper presents the study protocol for designing and evaluating an ePRO digital health application combined with proactive follow-up by nurses.Methods and analysis We designed a two-component intervention for women receiving breast cancer treatment: a responsive web application for monitoring ePROs and clinical algorithms guiding proactive follow-up by nurses. We will conduct a pilot test of the intervention with 50 patients with breast cancer for 6 weeks to assess feasibility and adjust the application. We will conduct a parallel arm randomised controlled trial assigning 205 patients each to intervention and control in one of Mexico’s largest public oncology hospitals. The intervention will be provided for 6 months, with additional 3 months of post-intervention observation. The control group will receive usual healthcare and a list of breast cancer information sources. Women diagnosed with stages I, II or III breast cancer who initiate chemotherapy and/or radiotherapy will be invited to participate. The primary study outcome will be supportive care needs; secondary outcomes include global quality of life and breast symptoms. Information on the outcomes will be obtained through web-based self-administered questionnaires collected at baseline, 1, 3, 6 and 9 months.Ethics and dissemination The National Research and Ethics Committees of the Mexican Institute of Social Security approved the study (R-2021-785-059). Participants will sign an informed consent form prior to their inclusion. Findings will be disseminated through a policy brief to the local authorities, a webinar for patients, publications in peer-reviewed journals and presentations at national and international conferences.Trial registration number NCT05925257.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Introduction.Melanoma is a public health problem; it represents 4% of malignant skin tumors and is responsible for 80% of deaths from this type of neoplasm. Objective: Show the response to Temozolomide in patients with metastatic melanoma. Methods: Descriptive, cross-sectional study. The clinical response of patients with metastatic melanoma, managed with Temozolomide 200 mg/m2 once a day was analyzed for 5 days every 28 days. The risk factors analyzed were: histological variety, topographic region of the primary lesion, metastasis, ulceration, and Breslow. Descriptive statistics were used for normality Kolmogorov-Smirnoff, Student's t-test, and binary logistic regression. Results: There were 51 les, 47 met the criteria; 25 men, 22 women, mean age 54.45, minimum 22, maximum 85 years, Complete response was obtained in 3 (6.3%), partial response in 7 (14.8%), stable disease in 10 (21%) and disease progression in 27 (57.44%) patients. The presence of ulceration is associated with a higher Breslow index and, as a result, a higher risk of disease progression. Conclusions: Temozolomide as monotherapy is a treatment that presents low rates of complete response and partial response, showing better results in patients with lymph node metastases.

Mycotoxins present a significant health concern within the animal-feed industry, with profound implications for the pig-farming sector. The objective of this study was to evaluate the efficacy of two commercial adsorbents, an organically modified clinoptilolite (OMC) and a multicomponent mycotoxin detoxifying agent (MMDA), to ameliorate the combined adverse effects of dietary aflatoxins (AFs: sum of AFB1, AFB2, AFG1, and AFG2), fumonisins (FBs), and zearalenone (ZEN) at levels of nearly 0.5, 1.0, and 1.0 mg/kg, on a cohort of cross-bred female pigs (N = 24). Pigs were randomly allocated into six experimental groups (control, mycotoxins (MTX) alone, MTX + OMC 1.5 kg/ton, MTX + OMC 3.0 kg/ton, MTX + MMDA 1.5 kg/ton, and MTX + MMDA 3.0 kg/ton), each consisting of four individuals, and subjected to a dietary regimen spanning 42 days. The administration of combined AFs, FBs, and ZEN reduced the body-weight gain and increased the relative weight of the liver, while there was no negative influence observed on the serum biochemistry of animals. The supplementation of OMC and MMDA ameliorated the toxic effects, as observed in organ histology, and provided a notable reduction in residual AFs, FBs, and ZEN levels in the liver and kidneys. Moreover, the OMC supplementation was able to reduce the initiation of liver carcinogenesis without any hepatotoxic side effects. These findings demonstrate that the use of OMC and MMDA effectively mitigated the adverse effects of dietary AFs, FBs, and ZEN in piglets. Further studies should explore the long-term protective effects of the studied adsorbent supplementation to optimize mycotoxin management strategies in pig-farming operations.

Abstract COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p 24.8 U/mL, p

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute painful conditions like post-operative and post-traumatic pain. Despite the satisfactory results achieved by oral analgesics, parenteral analgesia remains a key tool in the treatment of painful conditions when the enteral routes of administration are inconvenient. Parenteral ready-to-use fixed-dose combinations of non-opioid analgesics combinations, including NSAIDs and paracetamol or metamizole, could play a central role in the treatment of painful conditions by combining the advantages of multimodal and parenteral analgesia in a single formulation. Surprisingly, only in 2020, a parenteral ready-to-use fixed-dose combination of ibuprofen/paracetamol was launched to the market. This review aims to investigate the current availability of combinations of NSAIDs with paracetamol or metamizole in both European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, we explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. We concluded that, despite the well-recognized utility of combining NSAIDs with paracetamol or metamizole, several randomized clinical trial studies demonstrate no clear advantages concerning their efficacy and safety. Future clinical trials specifically designed to assess the efficacy and safety of pre-formulated fixed-dose combinations are required to generate solid evidence about their clinical advantages.

A utilização indiscriminada de antibacterianos no período gestacional pode aumentar a resistência antimicrobiana e colocar em risco a saúde da gestante e da criança. Atualmente, está em vigência no Brasil a Resolução da Diretoria Colegiada nº 20/2011, que controla a prescrição e fornecimento de antibacterianos. O objetivo deste estudo foi comparar o uso de antibacterianos pelas gestantes participantes das coortes de nascimentos de Pelotas, Rio Grande do Sul, Brasil, de 2004 e 2015, considerando a regulamentação implementada entre as duas coortes. Foram utilizados dados coletados no período perinatal dos dois estudos. O desfecho principal foi o uso de antibacterianos na gestação. As prevalências de uso foram descritas a partir de variáveis independentes e diferenças em pontos percentuais (p.p.) entre as duas coortes. A prevalência do uso de antibacterianos foi de 41,9% (IC95%: 40,4; 43,3) em 2004 e 39,2% (IC95%: 37,7; 40,6) em 2015. Considerando-se as gestantes que relataram ter infecção durante a gestação, observou-se maior redução de uso em 2015, quando comparado a 2004, nas gestantes mais pobres (-15,4p.p., IC95%: 9,59; 21,20) e naquelas que foram a menos consultas (-17,1p.p., IC95%: 2,81; 31,36). Houve redução na proporção de antibacterianos usados, considerando o total de medicamentos de 20,6% (IC95%: 19,9; 21,4) em 2004 para 12,6% (IC95%: 12,1; 13,1) em 2015. As reduções encontradas, tanto nas prevalências de uso quanto na proporção dos antibacterianos sobre o total de medicamentos utilizados, podem ser reflexo da política de regulamentação implementada em 2011.

Background: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. Materials and methods: This prospective cohort study included 262 consecutive adults with inflammatory bowel disease and rheumatological diseases who underwent an infectious diseases evaluation before initiating or switching immunosuppressive/biological therapy. Vaccine prescription and adherence were assessed during an infectious diseases (ID) consultation using a real-world multidisciplinary clinical project. Results: At baseline, less than 5% had all their vaccines up-to-date. More than 650 vaccines were prescribed to 250 (95.4%) patients. The most prescribed were pneumococcal and influenza vaccines, followed by hepatitis A and B vaccines. Adherence to each of the vaccines ranged from 69.1–87.3%. Complete adherence to vaccines occurred in 151 (60.4%) patients, while 190 (76%) got at least two-thirds of them. Twenty patients (8%) did not adhere to any of the vaccines. No significant differences were found in the adherence rates of patients with different sociodemographic and health-related determinants. Conclusions: ID physicians can play a role in the process of increasing vaccine prescription and adherence. However, more data on patients’ beliefs and vaccine hesitancy, along with mobilization of all health care professionals and adequate local interventions, shall be considered to improve vaccine adherence.

Abstract Objective The Glittre-ADL test (GA-T) is a functional capacity test that stands out for encompassing multiple tasks similar to activities of daily living. As ventilatory efficiency is one of the variables valued in the prognosis of chronic heart failure (CHF), this study aimed to evaluate associations between functional capacity and ventilatory variables in patients with CHF during the GA-T. Results Eight patients with CHF and New York Heart Association (NYHA) functional classification II–III underwent the GA-T coupled with metabolic gas analysis to obtain data by means of telemetry. The median total GA-T time was 00:04:39 (00:03:29–00:05:53). Borg dyspnoea scale scores before and after the GA-T were 2 (0–9) and 3 (1–10), respectively (P = 0.011). The relationship between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) was correlated with the total GA-T time (rs = 0.714, P = 0.047) and Borg dyspnoea score (rs = 0.761, P = 0.028). The other ventilatory variables showed no significant correlations. Our results suggest that the total GA-T time can be applied to estimate the ventilatory efficiency of patients with CHF. Future studies may use the GA-T in conjunction with other functional capacity tests to guide the treatment plan and evaluate the prognosis.

Bilateral luxatio erecta remains a rare condition, with less than 30 cases currently described in the literature. The authors present a case of bilateral inferior glenohumeral dislocation after a fall with low-energy trauma, treated with closed reduction and immobilization for 3 weeks followed by a physiotherapy program for functional rehabilitation. After 1 year of follow-up, the patient presented satisfactory results with a complete recovery of the previous mobility arch of both shoulders.

Abstract Background Low molecular weight carrageenan (Cg) is a seaweed-derived sulfated polysaccharide widely used as inflammatory stimulus in preclinical studies. However, the molecular mechanisms of Cg-induced inflammation are not fully elucidated. The present study aimed to investigate the molecular basis involved in Cg-induced macrophages activation and cytokines production. Methods Primary culture of mouse peritoneal macrophages were stimulated with Kappa Cg. The supernatant and cell lysate were used for ELISA, western blotting, immunofluorescence. Cg-induced mouse colitis was also developed. Results Here we show that Cg activates peritoneal macrophages to produce pro-inflammatory cytokines such as TNF and IL-1β. While Cg-induced TNF production/secretion depends on TLR4/MyD88 signaling, the production of pro-IL-1β relies on TLR4/TRIF/SYK/reactive oxygen species (ROS) signaling pathway. The maturation of pro-IL1β into IL-1β is dependent on canonical NLRP3 inflammasome activation via Pannexin-1/P2X7/K+ efflux signaling. In vivo, Cg-induced colitis was reduced in mice in the absence of NLRP3 inflammasome components. Conclusions In conclusion, we unravel a critical role of the NLRP3 inflammasome in Cg-induced pro-inflammatory cytokines production and colitis, which is an important discovery on the pro-inflammatory properties of this sulfated polysaccharide for pre-clinical studies. Video abstract Graphical Abstract Carrageenan (Cg) is one the most used flogistic stimulus in preclinical studies. Nevertheless, the molecular basis of Cg-induced inflammation is not totally elucidated. Herein, Lopes et al. unraveled the molecular basis for Cg-induced macrophages production of biological active IL-1β. The Cg-stimulated macrophages produces pro-IL-1β depends on TLR4/TRIF/Syk/ROS, whereas its processing into mature IL-1β is dependent on the canonical NLRP3 inflammasome.

To assess the effects of clinical-like cryotherapy on inflammatory signs (in vivo neutrophil migration, cytokines, and joint inflammation), pain, joint swelling, balance, and motor coordination in mice with knee arthritis. Young C57BL/6 mice were randomly divided into three groups (8 to 10 mice per group): Control group: mice with no intervention; antigen-induced arthritis (AIA) group: mice sensitized and immunized with intra-articular (i.a.) injection of methylated bovine serum albumin (mBSA); and AIA + cryotherapy group: mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol. After 21 days of sensitization, AIA and AIA + cryotherapy groups received i.a. injection of mBSA (100 μg/joint) to induce joint inflammation, and a clinical-like cryotherapy protocol was applied to AIA + cryotherapy group (crushed ice bag, two cryotherapy sessions of 20 min every two hours). Experimental analysis was conducted in the initial (immediately after i.a. injection of mBSA) and final periods (two hours after the second cryotherapy session). The number of synovial fluid neutrophils, cytokine levels, joint histology, pain, joint swelling, and motor performance were also analyzed. Our results showed that clinical-like cryotherapy in mice with acute knee arthritis reduced inflammatory signs, pain, and joint swelling, and improved balance and motor coordination.

To assess the effects of clinical-like cryotherapy on inflammatory signs (in vivo neutrophil migration, cytokines, and joint inflammation), pain, joint swelling, balance, and motor coordination in mice with knee arthritis. Young C57BL/6 mice were randomly divided into three groups (8 to 10 mice per group): Control group: mice with no intervention; antigen-induced arthritis (AIA) group: mice sensitized and immunized with intra-articular (i.a.) injection of methylated bovine serum albumin (mBSA); and AIA + cryotherapy group: mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol. After 21 days of sensitization, AIA and AIA + cryotherapy groups received i.a. injection of mBSA (100 μg/joint) to induce joint inflammation, and a clinical-like cryotherapy protocol was applied to AIA + cryotherapy group (crushed ice bag, two cryotherapy sessions of 20 min every two hours). Experimental analysis was conducted in the initial (immediately after i.a. injection of mBSA) and final periods (two hours after the second cryotherapy session). The number of synovial fluid neutrophils, cytokine levels, joint histology, pain, joint swelling, and motor performance were also analyzed. Our results showed that clinical-like cryotherapy in mice with acute knee arthritis reduced inflammatory signs, pain, and joint swelling, and improved balance and motor coordination.

Abstract Pyelocaliceal obstruction is a diagnostic challenge, and it is important to identify the obstruction cause. Some patients present extra‐renal compressive masses that need further imagiologic investigation and a biopsy, to establish the diagnosis.

Abstract Hemophagocytic lymphohistiocytosis poses a diagnostic dilemma due to the absence of specific clinical and laboratory findings, especially in adults. Despite greater recognition of the disease, secondary idiopathic forms are still reported.

Mycobacterium tuberculosis (M. tuberculosis) was the pathogen responsible for the highest number of deaths from infectious diseases in the world, before the arrival of the COVID-19 pandemic. Whole genome sequencing (WGS) has contributed to the understanding of genetic diversity, the mechanisms involved in drug resistance and the transmission dynamics of this pathogen. The object of this study is to use WGS for the epidemiological and molecular characterization of M. tuberculosis clinical strains from Chinchiná, Caldas, a small town in Colombia with a high incidence of TB. Sputum samples were obtained during the first semester of 2020 from six patients and cultured in solid Löwenstein-Jensen medium. DNA extraction was obtained from positive culture samples and WGS was performed with the Illumina HiSeq 2500 platform for subsequent bioinformatic analysis. M. tuberculosis isolates were typified as Euro-American lineage 4 with a predominance of the Harlem and LAM sublineages. All samples were proven sensitive to antituberculosis drugs by genomic analysis, although no phenotype antimicrobial tests were performed on the samples, unreported mutations were identified that could require further analysis. The present study provides preliminary data for the construction of a genomic database line and the follow-up of lineages in this region.

Bendamustine is a chemotherapeutic drug associated with frequent haematological and gastrointestinal adverse effects and, more rarely, neurological toxicity. We present the case of a 79-year-old man with follicular lymphoma, grade 2, Ann-Arbor stage IV-A, FLIPI 4, high risk, with bulky disease and vital organ compression, treated with R-CHOP and then rituximab-bendamustine, who developed encephalopathy approximately 2 months after the last cycle. After ruling out other possible aetiologies, we assumed the patient’s encephalopathy was due to a delayed bendamustine side effect, possibly aggravated by the concomitant administration of rituximab. The authors hope to alert clinicians to this rare adverse effect, its difficult identification and the need to rule out other aetiologies.

In this work, we propose a framework to store and manage spatial data, which includes new efficient algorithms to perform operations accepting as input a raster dataset and a vector dataset. More concretely, we present algorithms for solving a spatial join between a raster and a vector dataset imposing a restriction on the values of the cells of the raster; and an algorithm for retrieving K objects of a vector dataset that overlap cells of a raster dataset, such that the K objects are those overlapping the highest (or lowest) cell values among all objects. The raster data is stored using a compact data structure, which can directly manipulate compressed data without the need for prior decompression. This leads to better running times and lower memory consumption. In our experimental evaluation comparing our solution to other baselines, we obtain the best space/time trade-offs.

Background & aimsHepatorenal syndrome is a rare entity that is part of the complications of liver cirrhosis in its more severe stages. Without treatment, its mortality rate increases significantly. Terlipressin is considered to be the therapy of choice until the need of a liver transplant. The aim is to determine its prevalence, define patients' characteristics, triggers and 90-day survival, according to the type of managements established.MethodThis was a retrospective cohort study conducted in Colombia. It included patients with cirrhosis and acute kidney injury who met hepatorenal syndrome criteria, reaching 28 patients from 2007 to 2015. Groups were categorized according the type of hepatorenal syndrome and treatment. Demographic and trigger factors were evaluated to characterize the population. Treatment outcomes with terlipressin vs norepinephrine were analyzed up to a 90-day survival, using log Rank test. Continuous variables needed Student's T and Mann Whitney's U tests and categorical variables, Chi2 test. A value of p Results117 patients with cirrhosis developed renal injury; of these 23.9% were diagnosed with Hepatorenal Syndrome (67.8% type1; 32.1% type2). The presence of ascites was 100% in HRS2 and 84% in HRS1 (p = 0.296). The main trigger in both types was paracentesis greater than 5 liters in the last 4 weeks (39.3%). In total, 35% of the patients received renal replacement therapy and 14% underwent a hepatic transplant. Type 1 was more frequent (63% received terlipressin; 21% norepinephrine). The total complete response was 36% (Type2 66.6% vs. Type1 18.7%) (p = 0.026). In contrast, the overall mortality was of 67.8% at 90-day of follow-up (89.4% Type1 vs. 22% Type2) (p = ConclusionThere is scarce clinical and epidemiological information about this condition in Colombia. A significant difference between the two drugs cannot be stipulated due to the limitation in the sample size of our study. The general mortality at a 90-day follow-up was high, being higher in patients with HRS1. While the results of this study are suggestive of clinical information for HRS patients in the Colombian population, they should also be interpreted with caution, therefore further multicenter studies should be performed.

Introdução: O objectivo do presente estudo é o relato de um caso de variação anatómica do nervo isquiático, por origem baixa e divisão alta bilateral. Material e Métodos: Foi dissecado um cadáver feminino de 66 anos, conservado pelas técnicas originais desenvolvidas no nosso departamento. Resultados: No trabalho regular de dissecção cadavérica da disciplina de Anatomia Regional II detectou-se nervo isquiático, em ambos os membros, com pequeno trajecto, de aproximadamente, 8 - 10 cm, dividido em nervos fibular comum e tibial, ao nível da margem inferior do músculo glúteo máximo. Discussão: Casos semelhantes aos do presente estudo, foram descritos por alguns autores desde Leonardo da Vinci, Da Cortona, ou Eustachius, demonstrando a importância desse conhecimento, tanto em termos clínicos, como cirúrgicos ou anestesiológicos. Diversas ilações são possíveis, por revisão do presente caso, infrequente. Conclusão: Para além de proporcionar conhecimento prévio da anatomia loco-regional, o estudo das variações do nervo isquiático orienta o melhor seguimento de patologias, bem como acessos cirúrgicos e/ou anestésicos. Por mais meticulosos que sejam os nossos estudos anatómicos, jamais poderemos considerar terminada ou definitiva a investigação em anatomia humana.

Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara “Fray Antonio Alcalde”. To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski’s sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Introduction: Classical aphasia evaluation scales are too long to use in the context of acute stroke or as a monitoring tool. The Aphasia Rapid Test is a 26-point scale developed as a bedside assessment to rate aphasia severity in acute stroke patients in less than 3 minutes. We aimed to adapt and validate this scale for European Portuguese. Material and Methods: We evaluated 56 acute stroke patients in the first and in the seventh days post-stroke. In the seventh day, patients were evaluated by two independent raters, to evaluate inter-rater agreement. To study concurrent validity, the Lisbon Aphasia Examination Battery was applied to a subset of 20 patients. The predictive ability of the Aphasia Rapid Test was assessed at six months, by the aphasia subscale of the National Institutes of Health Stroke Scale. Results: Translation to European Portuguese was based in the French and English versions, considering the words’ utilization frequency. The Chronbach’s alpha was 0.796. The concordance coefficient between the two raters was excellent (0.985). Correlation between Aphasia Rapid Test and the Lisbon Aphasia Examination Battery was strong (r = -0.958, p < 0.001). The study through Bland-Altman graphs corroborated the good inter-rater agreement and concurrent validity of the test. The Aphasia Rapid Test score in the first day is an independent predictor of long-term outcome. Discussion: This study provides reliable results for European Portuguese, with adequate internal consistency, inter-rater agreement and concurrent validity. Conclusion: The Aphasia Rapid Test is a good tool for the evaluation and monitoring of aphasia in stroke patients.

Vaccination is the most effective public health intervention to prevent influenza infections, which are responsible for an important burden of respiratory illnesses and deaths each year. Currently, licensed influenza vaccines are mostly split inactivated, although in order to achieve higher efficacy rates, some influenza vaccines contain adjuvants. Although split-inactivated vaccines induce mostly humoral responses, tailoring mucosal and cellular immune responses is crucial for preventing influenza infections. Quillaja brasiliensis saponin-based adjuvants, including ISCOM-like nanoparticles formulated with the QB-90 saponin fraction (IQB90), have been studied in preclinical models for more than a decade and have been demonstrated to induce strong humoral and cellular immune responses towards several viral antigens. Herein, we demonstrate that a split-inactivated IQB90 adjuvanted influenza vaccine triggered a protective immune response, stronger than that induced by a commercial unadjuvanted vaccine, when applied either by the subcutaneous or the intranasal route. Moreover, we reveal that this novel adjuvant confers up to a ten-fold dose-sparing effect, which could be crucial for pandemic preparedness. Last but not least, we assessed the role of caspase-1/11 in the generation of the immune response triggered by the IQB90 adjuvanted influenza vaccine in a mouse model and found that the cellular-mediated immune response triggered by the IQB90-Flu relies, at least in part, on a mechanism involving the casp-1/11 pathway but not the humoral response elicited by this formulation.

Según las estadísticas oficiales, los hombres sufren más enfermedades profesionales (EEPP) que las mujeres. No obstante, hay que tener presente su desigual distribución y participación en el mundo laboral. El objetivo de este estudio fue valorar cómo afecta el sexo al reconocimiento de EEPP en España, identificando posibles factores de interacción/confusión. Métodos: Se estudió la incidencia de las EEPP declaradas a través del Parte Oficial durante el período de 1999 al 2009, proporcionados por la Subdirección General de Estadísticas Sociales y Laborales del Ministerio de Empleo y Seguridad Social. Las variables incluidas fueron: año de declaración, sexo, edad, ocupación y actividad económica de la empresa. Se calcularon tasas y riesgos relativos (RR) crudos de EEPP por cada variable. Se estimaron los RR ajustados mediante análisis bivariable y multivariante de Poisson. Resultados: Durante 1999-2009 se notificaron en España 243.310 EEPP, con una razón de tasas hombres/mujeres de 1,07. Hubo correlación entre la ocupación y la actividad de la empresa, por lo que se analizaron las EEPP según estas variables por separado. Por ocupación, los hombres presentaron un RR crudo de 1,067 (IC95%:1,058-1,076) frente a las mujeres, mientras que al ajustar por todas las variables del modelo el RR fue de 0,507 (IC95%:0,502-0,512). Por actividad, el sentido del riesgo también se invirtió en el análisis ajustado para el sexo (RRc=1,065, IC95%:1,056-1,074 frente a 0,632, IC95%:0,626-0,638). Conclusiones: Aunque las tasas crudas de EEPP son inferiores en mujeres que en hombres durante el periodo 1999-2009 en España, al ajustar estas tasas por la actividad de la empresa o la ocupación del trabajador, la edad y el año de declaración, los RR pasan a ser casi un 50% superiores en mujeres que en hombres para la mayoría de ocupaciones y tipos de actividad de la empresa.

Acute obstruction of superior vena cava anastomosis right after the Glenn procedure may lead to tragic consequences. We describe the case of a one-year-old child with tricuspid atresia and a previous Blalock-Taussig shunt procedure, who presented severe low cardiac output syndrome right after the Glenn procedure and died forty-four hours after the procedure. The autopsy showed obstruction of the superior vena cava anastomosis. Patients that present superior vena cava syndrome and low cardiac output right after the Glenn procedure should have the surgical anastomosis revised immediately.

PurposeThe Hortega Study is a prospective study, which investigates novel determinants of selected chronic conditions with an emphasis on cardiovascular health in a representative sample of a general population from Spain.ParticipantsIn 1997, a mailed survey was sent to a random selection of public health system beneficiaries assigned to the University Hospital Rio Hortega’s catchment area in Valladolid (Spain) (n=11 423, phase I), followed by a pilot examination in 1999–2000 of 495 phase I participants (phase II). In 2001–2003, the examination of 1502 individuals constituted the Hortega Study baseline examination visit (phase III, mean age 48.7 years, 49% men, 17% with obesity, 27% current smokers). Follow-up of phase III participants (also termed Hortega Follow-up Study) was obtained as of 30 November 2015 through review of health records (9.5% of participants without follow-up information).Findings to dateThe Hortega Study integrates baseline information of traditional and non-traditional factors (metabolomic including lipidomic and oxidative stress metabolites, genetic variants and environmental factors, such as metals), with 14 years of follow-up for the assessment of mortality and incidence of chronic diseases. Preliminary analysis of time to event data shows that well-known cardiovascular risk factors are associated with cardiovascular incidence rates, which add robustness to our cohort.Future plansIn 2020, we will review updated health and mortality records of this ongoing cohort for a 5-year follow-up extension. We will also re-examine elder survivors to evaluate specific aspects of ageing and conduct geolocation to study additional environmental exposures. Stored biological specimens are available for analysis of new biomarkers. The Hortega Study will, thus, enable the identification of novel factors based on time to event data, potentially contributing to the prevention and control of chronic diseases in ageing populations.

ABSTRACT Objective To evaluate whether hormonal profile, arterial function, and physical capacity are predictors of fatigue in patients with acromegaly. Subjects and methods: This is a cross-sectional study including 23 patients. The subjects underwent a Modified Fatigue Impact Scale (MFIS) assessment; serum growth hormones (GH) and IGF-1 measurements; pulse wave analysis comprising pulse wave velocity (PWV), arterial compliance (AC), and the reflection index (IR1,2); dominant upper limb dynamometry (DYN); and the six-minute walking distance test (6MWT). Multiple linear regression models were used to identify predictors for MFIS. The coefficient of determination R2 was used to assess the quality of the models’ fit. The best model was further analyzed using a calibration plot and a limits of agreement (LOA) plot. Results The mean ± SD values for the participants’ age, MFIS, PWV, AC, IR1,2, DYN, and the distance in the 6MWT were 49.4 ± 11.2 years, 31.2 ± 18.9 score, 10.19 ± 2.34 m/s, 1.08 ± 0.46 x106 cm5/din, 85.3 ± 29.7%, 33.9 ± 9.3 kgf, and 603.0 ± 106.1 m, respectively. The best predictive model (R2 = 0.378, R2 adjusted = 0.280, standard error = 16.1, and P = 0.026) comprised the following regression equation: MFIS = 48.85 - (7.913 × IGF-I) + (1.483 × AC) - (23.281 × DYN). Conclusion Hormonal, vascular, and functional variables can predict general fatigue in patients with acromegaly.

Background: Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus Tabebuia, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from Tabebuia rosea and Tabebuia chrysantha. Methods: The antioxidant activity of extracts obtained from the inner bark of T. rosea and T. chrysantha was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene (NQO1) was evaluated by real-time PCR. Results: The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of NQO1. Conclusion: These results indicate that the ethyl acetate extracts obtained from the inner bark of T. chrysantha and T. rosea have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.

There are controversies whether Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are distinct glomerular lesions or different manifestations within the same spectrum of diseases. The uPAR (urokinase-type plasminogen activator receptor) and some slit diaphragm proteins may be altered in FSGS glomeruli and may function as biomarkers of the disease in renal biopsies. Thus, this study aims to evaluate the diagnostic potential of uPAR and glomerular proteins for differentiation between MCD and FSGS in renal pediatric biopsy. Renal biopsies from 50 children between 2 and 18 years old were selected, with diagnosis of MCD (n = 29) and FSGS (n = 21). Control group consisted of pediatric autopsies (n = 15) from patients younger than 18 years old, with no evidences of renal dysfunction. In situ expressions of WT1, nephrin, podocin and uPAR were evaluated by immunoperoxidase technique. Renal biopsy of patients with MCD and FSGS expressed fewer WT1 (p≤0.0001, F = 19.35) and nephrin (p

Background: Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus Tabebuia, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from Tabebuia rosea and Tabebuia chrysantha. Methods: The antioxidant activity of extracts obtained from the inner bark of T. rosea and T. chrysantha was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene (NQO1) was evaluated by real-time PCR. Results: The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract, respectively). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of NQO1. Conclusion: These results indicate that the ethyl acetate extracts obtained from the inner bark of T. chrysantha and T. rosea have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.

The Iberian lynx (Lynx pardinus) is one of the most endangered felid species in the world. Conservation efforts have increased its population size and distribution and reinforced their genetic diversity through captive breeding and reintroduction programmes. Among several threats that the Iberian lynx faces, infectious and parasitic diseases have underlined effects on the health of their newly reintroduced populations, being essential to identify the primary sources of these agents and assess populations health status. To achieve this, 79 fresh faecal samples from Iberian lynx and sympatric mesocarnivores were collected in the reintroduction area of Extremadura, Spain. Samples were submitted to copromicroscopic analyses to assess parasite diversity, prevalence, and mean intensity of parasite burden. Overall, 19 (24.1%, ±15.1–35.0) samples were positive for at least one enteric parasite species. Parasite diversity and prevalence were higher in the Iberian lynx (43.8%) compared with the others mesocarnivores under study (e.g., the red fox Vulpes vulpes and the Egyptian mongoose Herpestes ichneumon). Ancylostomatidae and Toxocara cati were the most prevalent (15.6%) parasites. Obtained results revealed that Iberian lynx role as predator control might have reduced parasite cross-transmission between this felid and mesocarnivores due to their decreasing abundances. Surveillance programs must include regular monitoring of this endangered felid, comprising mesocarnivores, but also domestic/feral and wild cat communities.

Introducción: existen dos formas de respuesta tumoral a la quimioterapia neoadyuvante: concéntrica o dispersa. Los pacientes con respuesta dispersa no son buenos candidatos a cirugía conservadora porque sus microfocos tumorales pueden pasar desapercibidos en el tejido que rodea el tumor residual principal. Este tipo de respuesta se ha identificado como marcador de recurrencia ipsilateral luego de cirugía conservadora. Objetivo: el objetivo de este estudio es evaluar el porcentaje de respuesta de cada patrón y la suficiencia del margen obtenido en los casos de cirugía conservadora. Material y método: se analizaron los registros médicos de pacientes sometidos a cirugía luego de quimioterapia neoadyuvante entre mayo de 2004 y diciembre de 2013. Se efectuó un análisis detallado del tipo de quimioterapia recibida y de los informes patológicos para determinar el patrón de respuesta así como la de los fenotipos moleculares y el grado tumoral en cada caso. Resultados: 14 de los 55 casos (25%) presentaron un patrón de respuesta dispersa (diez con microfocos distantes de cáncer invasor y cuatro con microfocos distantes de cáncer in situ). El porcentaje de respuesta patológica completa fue de 15,4%. No hubo diferencias significativas en el tipo de respuesta entre los diferentes inmunofenotipos ni entre diferentes grados tumorales, ni entre las pacientes que recibieron taxanos y las que no los recibieron. Conclusiones: un cuarto de las pacientes de nuestra serie presentó un patrón de respuesta dispersa luego de quimioterapia neoadyuvante. Este es un signo de advertencia para aquellos que abogan por la cirugía conservadora luego de neoadyuvancia, ya que la respuesta difusa aumenta el riesgo de márgenes insuficientes y recurrencia ipsilateral.

Only a few studies describe histopathological changes in renal biopsies performed in pediatric patients. This study was conducted to identify an association between morphometric data in renal biopsies and renal function of these patients. Fifty-nine individuals with ages between 2 and 18 years old were selected, who were divided into six groups consisting of frequent nephropathies in children and adolescents and one control group. Proteinuria, urea, and creatinine values of the patients were recorded. Interactive image analysis software Leica QWin[®]was used for morpho- metric analysis of Bowman′s capsule, glomerular capillary tuft, and Bowman′s space area. The mean glomerular tuft area was higher in the membranous glomerulopathy group than in the podo- cytopathy group (57,101 ± 25,094 vs. 27,420 c ± 6279 µm2; P

Given a set of temporal networks, from different domains and with different sizes, how can we compare them? Can we identify evolutionary patterns that are both (i) characteristic and (ii) meaningful? We address these challenges by introducing a novel temporal and topological network fingerprint named Graphlet-orbit Transitions (GoT). We demonstrate that GoT provides very rich and interpretable network characterizations. Our work puts forward an extension of graphlets and uses the notion of orbits to encapsulate the roles of nodes in each subgraph. We build a transition matrix that keeps track of the temporal trajectory of nodes in terms of their orbits, therefore describing their evolution. We also introduce a metric (OTA) to compare two networks when considering these matrices. Our experiments show that networks representing similar systems have characteristic orbit transitions. GoT correctly groups synthetic networks pertaining to well-known graph models more accurately than competing static and dynamic state-of-the-art approaches by over 30%. Furthermore, our tests on real-world networks show that GoT produces highly interpretable results, which we use to provide insight into characteristic orbit transitions.

A randomized controlled trial was performed on racing horses, to evaluate the efficacy of a new class of therapeutic agents in regenerative medicine-ReGeneraTing Agents® (RGTA®), to treat tendinopathies. Preliminary uncontrolled studies on tendon healing in racing horses with RGTA® (OTR4131)-Equitend® showed encouraging results, justifying performing a randomized, controlled, multicenter study with a two-year racing performance follow up. The objective of this study was to evaluate the effect of Equitend® versus placebo on acute superficial digital flexor tendonitis in racing French Standardbred Trotters (ST). Twenty-two ST were randomly and blindly assigned to receive with a ratio of 2 to 1, a single Equitend® (n = 14) or placebo (n = 8) intralesional injection under ultrasonographic guidance. Horses were evaluated over 4 months, by clinical and ultrasonographic evaluations (day 0, months 1, 2, 4), and their racing performances followed up over the 2 years after treatment. During the first month of treatment, a significant decrease in the cross-sectional area (CSA) was found in the Equitend® group (p = 0.04). After 4 months, the number of Equitend® treated horses with an improved CSA was significantly higher than the placebo-treated horses (p = 0.03571). The Equitend® group returned to their pre-injury performance level, racing in, and winning, significantly more races than the placebo group (p = 0.01399 and 0.0421, respectively). Furthermore, recurrence was significantly higher in the placebo group than in the Equitend® group (71.4% vs 16.6%, p = 0.02442). In conclusion, we measured a significant, short-term, reduction effect on CSA and demonstrated a long-term beneficial effect of intralesional injection of Equitend® for the treatment of superficial digital flexor tendonitis on racing ST, racing 2. 3 times more often than placebo, with 3.3 times fewer recurrences maintaining pre-injury performance level. This study may open the way for the development of a human treatment of tendonitis.

Desde las epidemias de peste en la edad media hasta la epidemia de Ébola en África del Oeste en 2014-15, las emergencias sanitarias han tenido un impacto importante en la historia de la humanidad. Sin embargo, a partir de la segunda mitad del siglo XX la frecuencia con la que se detectan y notifican eventos y situaciones de riesgo para la salud de la población a nivel global parece haberse incrementado. Durante ese mismo periodo, se ha producido un cambio global en diversos ámbitos, incluyendo el clima que dada la velocidad a la que se está desarrollando puede poner en duda la capacidad de adaptación del ser humano. En este artículo tratamos de valorar las relaciones existentes entre el cambio global y la modificación observada en el patrón de las alertas y emergencias de interés internacional y planteamos el posible impacto de este cambio de patrón. Si bien a corto plazo este impacto podría ser controlable, la complejidad de las interrelaciones entre los diferentes aspectos del cambio global y sus posibles sinergias y su impacto en la salud humana dificultan predicciones a medio y largo plazo.

Desde las epidemias de peste en la edad media hasta la epidemia de Ébola en África del Oeste en 2014-15, las emergencias sanitarias han tenido un impacto importante en la historia de la humanidad. Sin embargo, a partir de la segunda mitad del siglo XX la frecuencia con la que se detectan y notifican eventos y situaciones de riesgo para la salud de la población a nivel global parece haberse incrementado. Durante ese mismo periodo, se ha producido un cambio global en diversos ámbitos, incluyendo el clima que dada la velocidad a la que se está desarrollando puede poner en duda la capacidad de adaptación del ser humano. En este artículo tratamos de valorar las relaciones existentes entre el cambio global y la modificación observada en el patrón de las alertas y emergencias de interés internacional y planteamos el posible impacto de este cambio de patrón. Si bien a corto plazo este impacto podría ser controlable, la complejidad de las interrelaciones entre los diferentes aspectos del cambio global y sus posibles sinergias y su impacto en la salud humana dificultan predicciones a medio y largo plazo.

El hipertiroidismo es una de las enfermedades endocrinológi - cas más frecuentes cuyo tratamiento actual se basa en fárma - cos, yodo radioactivo y cirugía. El metimazol es usualmen - te el antitiroideo de elección debido a su potencia y efectos adversos infrecuentes, generalmente leves. Este medicamento rara vez se asocia a toxicidad hepática que por lo general suele manifestarse con ictericia colestásica. Presentamos el caso de una paciente de 33 años que acude al Hospital Uni - versitario Fundación Santa Fe de Bogotá con ictericia coles - tásica inducida por el tratamiento con metimazol para una enfermedad de Graves. El prurito e ictericia apareció después de tres semanas de tratamiento, todos los marcadores de he - patitis virales fueron negativos, la ecografía hepatobiliar fue normal y se observó una elevación de la fosfatasa alcalina, la bilirrubina total y las aminotransferasas. El diagnóstico de causalidad de hepatotoxicidad inducida por el metimazol fue apoyado por la biopsia hepática. Según la escala CIOMS se obtuvo una puntuación de 10. De este modo la relación causal de la reacción adversa hepática asociada a metimazol es muy probable. El curso clínico de la paciente fue satisfac - torio tras la interrupción del fármaco, con mejoría clínica a los 5 días y normalización de las pruebas hepáticas a las 5 semanas. El presente caso se discute desde una aproximación diagnóstica y terapéutica.

El dengue se ha convertido en un importante problema de salud pública mundial. Ae. Albopictus, vector competente para su transmisión, se detectó por primera vez en Cataluña en 2004. Desde entonces se ha establecido por la costa Mediterránea. El objetivo del artículo es describir el riesgo de importación y posible transmisión del dengue en España, revisando cualitativamente los factores que podrían influir en su emergencia en nuestro país, así como las implicaciones que tendría a nivel de salud pública. Aunque el virus no circula actualmente en España, constante- mente llegan personas infectadas procedentes de países endémicos. La transmisión de esta enfermedad podría ocurrir en la costa mediterránea. Sería más probable en los meses más cálidos por los hábitos socioculturales y las mayor presencia del vector. Aunque la mayoría de la población es susceptible, el impacto en la salud de la población sería bajo dadas las características de la enfermedad. La estrategia fundamental de salud pública para reducir el riesgo de importación y posible transmisión del dengue de- be enfocarse a la prevención primaria para evitar la interacción del virus, el vector y los seres humanos. Estos tres componentes deben abordarse dentro de un plan de acción integral y multisectorial, intensificando algunas actividades en las zonas de mayor riesgo. La coordinación desde salud pública de todos los sectores implicados es imprescindible para el correcto funcionamiento de este plan integral de respuesta ante enfermedades transmitidas por vectores.

Fundamentos: Después de la ola de calor del año 2003 muchos países euro- peos implementaron planes para la vigilancia y control de los efectos de las olas de calor (PVCEOC), sin embargo, son pocos los países que han evaluado su impacto. El objetivo de trabajo es evaluar el impacto del PVEOC en la mortalidad atribuida al calor. Método: Para evaluar en la ciudad de Madrid la mortalidad atribuida al calor durante el período 1990-2009 se realizó un análisis de series temporales utili- zando modelos ARIMA con una variable exógena, la temperatura.Se analizó el impacto de las altas temperaturas sobre la mortalidad antes y después de 2004, año de la implementación del PVCEOC. Resultados: El impacto atribuible a la ola de calor en el año 2003 fue del 22,39 % de incremento de mortalidad por cada oC que se superó la tempera- tura umbral, con una intensidad de 8,2 oC. Algunas olas de calor previas al 2003 fueron superiores en intensidad, así durante los años 1991, 1992 y 1995 la intensidad de las olas de calor fue de 25,9 oC, 8,3 oC y 12,5 oC respectiva- mente. Las olas de calor posteriores al 2003 presentaron menor intensidad y en 2005 con una ola de calor de 4,5 oC de intensidad se observó un impacto de 45,71% de incremento de la mortalidad por cada oC en que se superó la tem- peratura umbral. Conclusiones: Con la metodología utilizada no se puede afirmar que en Ma- drid la puesta en marcha del PVEOC se traduzca en una disminución de la mortalidad atribuible a las altas temperaturas .

n/a

Swarm robotics is a promising approach for the coordination of large numbers of robots. While previous studies have shown that evolutionary robotics techniques can be applied to obtain robust and efficient self-organized behaviors for robot swarms, most studies have been conducted in simulation, and the few that have been conducted on real robots have been confined to laboratory environments. In this paper, we demonstrate for the first time a swarm robotics system with evolved control successfully operating in a real and uncontrolled environment. We evolve neural network-based controllers in simulation for canonical swarm robotics tasks, namely homing, dispersion, clustering, and monitoring. We then assess the performance of the controllers on a real swarm of up to ten aquatic surface robots. Our results show that the evolved controllers transfer successfully to real robots and achieve a performance similar to the performance obtained in simulation. We validate that the evolved controllers display key properties of swarm intelligence-based control, namely scalability, flexibility, and robustness on the real swarm. We conclude with a proof-of-concept experiment in which the swarm performs a complete environmental monitoring task by combining multiple evolved controllers.

Fundamento: El sistema español de monitorización de la mortalidad y el «Programa Europeo de monitorización de excesos de mortalidad para la acción en salud pública» detectaron dos excesos de mortalidad en España en noviembre y diciembre de 2009. El objetivo de este trabajo es valorar su posible asociación con la transmisión de gripe pandémica. Métodos: Se analizó la evolución de la mortalidad en España en los meses citados utilizando métodos de análisis de series temporales basados en las series históricas de mortalidad y se comparó en el tiempo con la transmisión de gripe. Resultados: La mortalidad observada en la población total fue mayor de lo esperado en dos periodos: semanas 46-47/2009 con 5,75% de exceso y las semanas 51-52/2009 con 7,35% de exceso. También se registró un exceso de mortalidad en niños de 5 a 14 años en las semanas 46-48/2009 con 41 defunciones vs las 21 esperadas. El exceso de mortalidad en noviembre fue concomitante con las mayores tasas de gripe. El exceso de diciembre se observó 5 semanas después del pico de gripe y coincidió con un descenso dramático de las temperaturas. El virus sincitial respiratorio y los accidentes de tráfico fueron descartados como factores asociados. Conclusiones: Mientras que las temperaturas podrían explicar la mayoría del exceso de mortalidad observado en diciembre, ningún factor por si solo podría explicar el exceso de noviembre.

Fundamentos: La incidencia de tuberculosis (TB) se ha asociado a factores, epidemiológicos y sociales. En España, la TB es una enfermedad de declaración obligatoria e individualizada. Las tasas de TB respiratoria experimentan un descenso constante en los últimos años. El objetivo es valorar la asociación entre la morbilidad por TB respiratoria y variables socioeconómicas y epidemiológicas así como su distribución espacial mediante métodos geoestadísticos. Método: Las tasas de incidencia se estandarizaron por edad y sexo con datos de la Red Nacional de Vigilancia (2006). Las variables socioeconómicas incluidas son: condición socioeconómica, nivel de estudios, tasa de hacinamiento, densidad de población, tasa de inmigración estandarizada por sexo, tasa de analfabetismo, tasa de paro, gasto medio en euros por persona. Las variables epidemiológicas incluidas han sido la tasa de SIDA y la tasa de incidencia de gripe. Se realizó un análisis multivariable mediante un Modelo Lineal Generalizado poisson. Se aplicó la técnica geoestadística Cokringing ajustada por las variables estadísticamente significativas para ver la distribución espacial de riesgo. Resultados: Las variables estadísticamente significativas son la tasa de hacinamiento, tasa de inmigración, tasa de analfabetismo, tasa de paro, gasto medio euros por persona, tasa de gripe y tasa de sida. La técnica geoestadística muestra una variabilidad espacial del riesgo y una concentración del riesgo en el noroeste y sureste de la península. Conclusiones: Los resultados permiten afirmar que el método Cokriging es una herramienta útil para representar la distribución espacial del riesgo. Existe asociación entre variables socioeconómicas, epidemiológicas y TB en España.

The interaction between blood-borne pathogens and fibrinolysis is one of the most important mechanisms that mediate invasion and the establishment of infectious agents in their hosts. However, overproduction of plasmin (final product of the route) has been related in other contexts to proliferation and migration of the arterial wall cells and degradation of the extracellular matrix. We have recently identified fibrinolysis-activating antigens from Dirofilaria immitis, a blood-borne parasite whose key pathological event (proliferative endarteritis) is produced by similar mechanisms to those indicated above. The objective of this work is to study how two of this antigens [actin (ACT) and fructose-bisphosphate aldolase (FBAL)] highly conserved in pathogens, activate fibrinolysis and to establish a relationship between this activation and the development of proliferative endarteritis during cardiopulmonary dirofilariasis. We demonstrate that both proteins bind plasminogen, enhance plasmin generation, stimulate the expression of the fibrinolytic activators tPA and uPA in endothelial cell cultures and are located on the surface of the worm in contact with the host's blood. ELISA, western blot and immunofluorescence techniques were employed for this purpose. Additionally, the implication of lysine residues in this interaction was analyzed by bioinformatics. The involvement of plasmin generated by the ACT/FBAL and plasminogen binding in cell proliferation and migration, and degradation of the extracellular matrix were shown in an "in vitro" model of endothelial and smooth muscle cells in culture. The obtained results indicate that ACT and FBAL from D. immitis activate fibrinolysis, which could be used by the parasite like a survival mechanism to avoid the clot formation. However, long-term overproduction of plasmin can trigger pathological events similar to those described in the emergence of proliferative endarteritis. Due to the high degree of evolutionary conservation of these antigens, similar processes may occur in other blood-borne pathogens.

In cattle, molecular control of oviduct receptivity to the embryo is poorly understood. Here, we used a bovine model for receptivity based on size of the pre-ovulatory follicle to compare oviductal global and candidate gene transcript abundance on day 4 of the estrous cycle. Growth of the pre-ovulatory follicle (POF) of Nelore (Bos indicus) cows was manipulated to produce two groups: large POF large corpus luteum (CL) group (LF-LCL; greater receptivity) and small POF-small CL group (SF-SCL). Oviductal samples were collected four days after GnRH-induced ovulation. Ampulla and isthmus transcriptome was obtained by RNA-seq, regional gene expression was assessed by qPCR, and PGR and ERa protein distribution was evaluated by immunohistochemistry. There was a greater abundance of PGR and ERa in the oviduct of LF-LCL animals thus indicating a greater availability of receptors and possibly sex steroids stimulated signaling in both regions. Transcriptomic profiles indicated a series of genes associated with functional characteristics of the oviduct that are regulated by the periovulatory sex steroid milieu and that potentially affect oviductal receptivity and early embryo development. They include tissue morphology changes (extra cellular matrix remodeling), cellular changes (proliferation), and secretion changes (growth factors, ions and metal transporters), and were enriched for the genes with increased expression in the LF-LCL group. In conclusion, differences in the periovulatory sex steroid milieu lead to different oviductal gene expression profiles that could modify the oviductal environment to affect embryo survival and development.