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Lina Marcela Parra,1 Mireia Cantero,1 Ignacio Morrás,2 Alberto Vallejo,1 Itziar Diego,2 Elena Jiménez-Tejero,1 Elena Múñez,3 Ángel Asensio,1 Ana Fermández-Cruz,3,4 Antonio Ramos-Martinez3,4 On behalf of Puerta de Hierro Hospital Admission Study Group1Servicio de Medicina Preventiva, HU Puerta de Hierro-Majadahonda, Madrid, Spain; 2Servicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Madrid, Spain; 3Servicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Unidad de Enfermedades Infecciosas, UAM, Madrid, Spain; 4Instituto Investigación Sanitaria Puerta de Hierro - Segovia de Arana (IDIPHSA), Madrid, SpainCorrespondence: Antonio Ramos-MartinezServicio de Medicina Interna, HU Puerta de Hierro-Majadahonda, Unidad de Enfermedades Infecciosas, Calle Joaquín Rodrigo 2, Majadahonda, Madrid 28222, SpainTel +34 638 211 120Fax +34 91191 6807Email aramos2202@gmail.comObjective: To analyse the rate of occurrence and the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19.Setting: University hospital in Madrid (Spain).Participants: Sixty-one patients (74% male) who presented COVID-19 were readmitted during the 3 weeks after discharge from hospital.Interventions: Nested case–control study paired (1:1 ratio) by age, sex and period of admission.Outcome Measures: Rate of readmission rate of patients discharged after suffering COVID-19 and identification of the clinical variables associated with it.Results: Out of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients (N=10.2%) were at increased risk for readmission (p=0.04). There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil-to-lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate. Patients who were readmitted due to a thrombotic event (8 patients, 13.1%) presented a higher level of D-dimer at discharge of initial admission.Conclusion: The rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge were at greater risk of readmission to hospital.Keywords: coronavirus, pneumonia, viral, patient readmission, pulmonary embolism, heparin

In this study, the transport of salt with moderate solubility through bioinspired solid-state nanochannels was comprehensively investigated. For this purpose, bullet-shaped channels were fabricated and exposed to KClO 4 , a monovalent salt with moderate solubility. These channels displayed the typical rectifying behavior characteristic of asymmetrical channels but with one remarkable difference, the iontronic output exhibited a negative incremental resistance phenomenon of high gating efficiency when the transmembrane voltage in the open state was increased enough, giving rise to an inactivated state characterized by a low and stable ion current. The behavior is attributed to salt precipitation inside the channel and remarkably, it is not observed in other geometries such as cylindrical or cigar-shaped channels. Considering the central role of the surface in precipitation formation, the influence of several parameters such as electrolyte concentration, pH, and channel size was studied. Under optimized conditions, this system can alternate among three different conductance states (closed, open, and inactivated) and exhibits gating ratios higher than 20. Beyond its potential application in fields related to electronics or sensing, this study provides valuable insight into the fundamental principles behind ion rectifying behavior in solid-state channels and highlights the implications of surface phenomena at the nanoscale.

Background: Key and core components of effective infection prevention and control programmes (IPCPs) issued by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) have been described. WHO core component 1 relates to the structure, organization and management of IPCPs., Aim: The objective of this study was to assess the status and the time trends of some indicators of core component 1 of IPCPs in acute hospitals in Spain throughout the period 2012-2022., Methods: Hospital-level data from the Spanish point prevalence survey for years 2012-2022 were analysed. Core component 1 indicators were calculated and tested for association to healthcare-associated infections (HAIs). In addition, trends were also examined., Results: Overall, 67.0% and 57.2% of Spanish hospitals reported having an annual infection prevention and control (IPC) plan and an annual IPC report that was approved by the hospital managing director, respectively. The global median number of full-time equivalent (FTE) IPC nurses per 250 beds for the period was 0.87 and the global median number of FTE IPC doctors was 0.70. The rates of blood cultures and stool tests for Clostridioides difficile were 39.9 and 6.1 per 1000 patient-days, respectively. No significant correlation was found between core component 1 indicators and HAI prevalence., Conclusion: Spain is currently at a basic level on the structure, organization and management of IPCPs. Profound differences were found between hospitals depending on size and type., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Surveillance of antimicrobial consumption is an important component of control strategies to tackle antimicrobial resistance., Aim: To evaluate the consumption of antimicrobials using six indicators proposed by the European Center for Disease Prevention and Control., Methods: Point prevalence survey data on antimicrobial use in Spanish hospitals throughout the period 2012-2021 were analysed. A descriptive analysis of each indicator by year was performed globally and by hospital size. A logistic regression model was used to identify significant time trends., Findings: In all, 515,414 patients and 318,125 antimicrobials were included. The prevalence of antimicrobial use remained stable throughout the study period (45.7%; 95% confidence interval (CI): 45.6-45.8). Percentages of antimicrobials for systemic use and those administered parenterally showed a small and significant increasing trend (odds ratio (OR): 1.02; 95% CI: 1.01-1.02; and OR: 1.03; 95% CI: 1.02-1.03, respectively). Small improvements were found in the percentages of antimicrobials prescribed for medical prophylaxis and with the reason for use documented in patients' medical records (-0.6% and 4.2%, respectively). The percentage of surgical prophylaxis prescribed for more than 24 h shows a significant improvement, decreasing from 49.9% (95% CI: 48.6-51.3) in 2012 to 37.1% (95% CI: 35.7-38.5) in 2021., Conclusion: During the last decade, Spanish hospitals have had a stable but high prevalence of antimicrobial use. Little to no improvement has been made in most of the indicators analysed, except for a reduction in the prescription of surgical prophylaxis for more than 24 h., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The parasitoid Telenomus podisi Ashmead, 1893 is used in biological control programs in Brazil against eggs of Euschistus heros (Fabricius, 1798), a key pest of soybean, Glycine max (L.) Merr. To optimize the mass production of parasitoids, artificial diets and storage of host eggs at low temperatures have been developed; however, direct comparisons of the effects of these conditions have not occurred. We assessed a double factorial arrangement composed of six treatments (fresh or cryopreserved E. heros eggs from adults fed on natural or two artificial diets). We evaluated the biological characteristics and parasitism capacity of T. podisi produced from these treatments across seven temperatures. The thermal range between 21 and 30 °C resulted in satisfactory daily parasitism in all treatments tested, with an inverse relationship between temperature and female survival. The best parasitoid biological parameters were found between 21 and 27 °C, where all tested diets supported T. podisi development, with the best results from artificial diets. Fresh eggs and those frozen in liquid nitrogen and stored at -196 °C until use supported parasitoid development. These results suggest that the best method to mass rear T. podisi is to use artificial diets to rear E. heros and store eggs until needed, and then rear parasitoids at 24 °C.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (p = 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (p = 0.042) and the HLA-G expression with progression to death (p = 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Colombian program to end trachoma implements the component F of the SAFE strategy in the Vaupés department of the Amazon rainforest. Cultural, linguistic, and geographical barriers and the coexistence of an ancestral medical system demand the technical and sociocultural adaptation of this component. A cross-sectional survey combined with focus-group discussions to understand the knowledge, attitudes, and practices of the indigenous population related to trachoma was conducted in 2015. Of the 357 heads of households that participated, 45.1% associated trachoma with a lack of hygiene, and 94.7% associated the concept of hygiene with taking one or more body baths per day, using commercial or handcrafted soap. In total, 93% reported cleaning their children's faces and eyes more often when they have conjunctivitis, but 66.1% also did this with clothes or towels in use, and 52.7% of people shared towels; in total, 32.8% indicated that they would use ancestral medicine to prevent and treat trachoma. The SAFE strategy in Vaupés requires an intercultural approach to facilitate stakeholder support and participation to promote general and facial hygiene, washing clothes with soap, and not sharing towels and clothes to dry and clean children's faces for effective and sustainable elimination of trachoma as a public health problem. This qualitative assessment facilitated an intercultural approach locally and in other Amazonian locations.

The expansion of Integrated Pest Management (IPM), including biological control, has had several positive consequences for the agricultural environment and participants in the production chain. To enable successful operation and applications of biological control, production of insects used for rearing natural enemies (parasitoids and predators) must be optimized to reduce time and costs and improve production both qualitatively and quantitatively. The present study evaluated the effect of wheat varieties, the main component of artificial diets for Ephestia kuehniella, on the reproductive performance and biological parameters of this flour moth, which is used for mass production of Trichogramma spp. (Hymenoptera: Trichogrammatidae) and other parasitoids and predators. Four varieties of wheat were compared: BRS 327, BRS Marcante, BRS Parrudo, and KBR, with and without the addition of corn E. kuehniella reared on 97% BRS 327 wheat flour + 3% nutritional yeast had the best biological parameters and substitution of corn for about half of the wheat increased the number of eggs per female., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America.)

Background: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data., Methods: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI., Results: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age., Conclusion: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making., (Copyright © 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Healthcare workers (HCWs) have been a critical and vulnerable population during SARS-CoV-2 pandemic. The aim of this study was to determine the overall seroprevalence and to evaluate occupational risk factors among HCWs in one of the countries most affected by this pandemic., Methods: We conducted a seroprevalence study for SARS-CoV-2 in a tertiary hospital in Madrid (Spain) between 24 April and 8 May 2020. A total of 4894 HCWs were invited for serologic testing. Serum samples were tested for SARS-CoV-2 IgM and IgG antibodies using Enzyme Immunoassay (ELISA) and Electro-Chemiluminescence Immunoassay (ECLIA) techniques. We calculated odds ratios to assess association between demographic and occupational characteristics with SARS-CoV-2 seroconversion., Results: We processed 4324 serum samples. Overall, seroprevalence was of 16.6% (95% CI: 15.5-17.7). We found statistically significant differences in SARS-CoV-2 seroprevalence by type of employee, professional category, department and type of activity performed during the pandemic period, while no differences were identified between the personnel working in the COVID-19 wards compared to those working in non-COVID-19 wards. We confirmed 268 (26.7%) infections among 1005 hospital staff members tested by PCR. 60.5% of HCWs infected by SARS-CoV-2, assessed either by PCR or serology, could be considered asymptomatic or paucisymptomatic., Conclusions: HCWs have an increased risk of SARS-CoV-2 infection but COVID-19 patient exposure was not a determining factor. Universal mask wearing should be mandatory in healthcare settings given the important number of asymptomatic and paucisymptomatic cases.

Background: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data., Methods: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI., Results: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age., Conclusion: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making., (Copyright © 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Publicado por Elsevier España, S.L.U. All rights reserved.)

In this meta-analysis, central venous catheter exposure (pooled odds ratio, 8.02; 95% confidence interval [CI], 2.19-29.31; P < .01) in neonates and length of stay (standardized mean difference, 0.65; 95% CI, 0.26-1.05; P = .01) in an adult population were associated with acquisition of waterborne healthcare-associated infections or colonization in ICUs. The quality of evidence was low.

Background: We describe the management and control of an outbreak of mediastinitis in a cardiac surgery department. Method: We performed a retrospective cohort study of 87 patients who underwent coronary artery bypass grafting (CABG), valve replacement, or both during a five-month period with a higher than normal number of cases of post-operative mediastinitis. In addition to medical records review, a survey was conducted among surgeons to estimate the frequency of cellulose-derived absorbable hemostatic (CDAH) use. Results: Eleven patients (12.5%) developed mediastinitis during the period. None of them died, and the course of the infections was benign. No differences were found between the infected and non-infected patients regarding clinical or demographic characteristics. The rate of infection by surgeon ranged from 0 to 21.4%. (p = 0.38). We found a significant linear relation between the frequency of CDAH use and the risk of infection, from 3.3% to 22.6% (p = 0.024). Cultures of unused CDAHs were negative. Cessation of product use led to no new cases for the following year and to a mediastinitis rate <1% for the following 24 months. Conclusion: We identified a cluster of undesired clinical outcomes compatible with mediastinitis that added morbidity and associated cost, but not deaths, related to the use of CDAH as a hemostatic. These data suggest keeping the use of CDAH in cardiothoracic surgery to a minimum.

Objective: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes., Materials and Methods: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development., Results: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them., Conclusions: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

In this outbreak, 12 patients in intensive care units acquired a Chryseobacterium indologenes infection. Cultures from sinkholes and air samples were positive for C. indologenes. After removing wash basins, no new cases appeared. Sinkholes, potentially contaminated, can act as a reservoir for C. indologenes and other microorganisms. Thus, patients and equipment should be protected from sink splashes to avoid contamination.

The linkage disequilibrium (LD) between molecular markers affects the accuracy of genome-wide association studies and genomic selection application. High-density genotyping platforms allow identifying the genotype of thousands of single nucleotide polymorphisms (SNPs) distributed throughout the animal genomes, which increases the resolution of LD evaluations. This study evaluated the distribution of minor allele frequencies (MAF) and the level of LD in the Colombian Creole cattle breeds Blanco Orejinegro (BON) and Romosinuano (ROMO) using a medium density SNP panel (BovineSNP50K&#95;v2). The LD decay in these breeds was lower than those reported for other taurine breeds, achieving optimal LD values (r2 ≥ 0.3) up to a distance of 70 kb in BON and 100 kb in ROMO, which is possibly associated with the conservation status of these cattle populations and their effective population size. The average MAF for both breeds was 0.27 ± 0.14 with a higher SNP proportion having high MAF values (≥ 0.3). The LD levels and distribution of allele frequencies found in this study suggest that it is possible to have adequate coverage throughout the genome of these breeds using the BovineSNP50K&#95;v2, capturing the effect of most QTL related with productive traits, and ensuring an adequate prediction capacity in genomic analysis.

Several coastal lagoons and estuaries in Mexico receive untreated domestic and industrial discharges which contain complex mixtures of contaminants. In order to assess the effects of chemical contamination, we used the White mullet (Mugil curema) as biological indicator. We worked in two estuaries located in Northwest Mexico: Urias (highly polluted) and Teacapan (less polluted, therefore used as reference site). We measured several endpoints at different levels of biological organization: vitellogenin transcription in males as biomarker of estrogenic contamination, as well as reproductive, morphological (deformities), morphometric, and meristic parameters. Total RNA was isolated from the liver, and a partial sequence of the mullet vitellogenin gene was obtained; gene expression was analyzed by quantitative PCR. At the same time, gonad samples were analyzed by histologic techniques to determine sex ratios and the reproductive cycle stage. The reproductive season was detected from February to June in both sites, but the gonadosomatic index was consistently higher in Teacapan. Sex ratios were female-biased in both estuaries, and one intersex gonad and several malformations were found in fish from Urias. Vitellogenin gene transcription in males was detected in both sites, although gene expression was slightly higher in Urias. The results obtained in this study indicate that biological effects of contamination are evident in fish, environmental estrogens may be present in both estuaries, and the white mullet is useful as biological indicator to identify and characterize environmental stressors in tropical coastal ecosystems.

Release of cytokines, growth factors and other life-essential molecules from precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high substrate-specificity. We hypothesized that this is achieved by cleavage-regulatory intracellular-domain (ICD)-modifications of the precursors. We show here that cleavage-stimuli-induced specific ICD-modifications cause structural substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1; epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to chymotrypsin/trypsin or soluble ADAM. This inside-out signal transfer required substrate homodimerization and was prevented by cleavage-inhibitory ICD-mutations. In chimeras, regulation could be conferred to a foreign ectodomain, suggesting a common higher-order structure. We predict that substrate-specific protease-accessibility-regulation controls release of numerous ADAM substrates.

Ectodomain cleavage by A-disintegrin and -metalloproteases (ADAMs) releases many important biologically active substrates and is therefore tightly controlled. Part of the regulation occurs on the level of the enzymes and affects their cell surface abundance and catalytic activity. ADAM-dependent proteolysis occurs outside the plasma membrane but is mostly controlled by intracellular signals. However, the intracellular domains (ICDs) of ADAM10 and -17 can be removed without consequences for induced cleavage, and so far it is unclear how intracellular signals address cleavage. We therefore explored whether substrates themselves could be chosen for proteolysis via ICD modification. We report here that CD44 (ADAM10 substrate), a receptor tyrosine kinase (RTK) coreceptor required for cellular migration, and pro-NRG1 (ADAM17 substrate), which releases the epidermal growth factor (EGF) ligand neuregulin required for axonal outgrowth and myelination, are indeed posttranslationally modified at their ICDs. Tetradecanoyl phorbol acetate (TPA)-induced CD44 cleavage requires dephosphorylation of ICD serine 291, while induced neuregulin release depends on the phosphorylation of several NRG1-ICD serines, in part mediated by protein kinase Cδ (PKCδ). Downregulation of PKCδ inhibits neuregulin release and reduces ex vivo neurite outgrowth and myelination of trigeminal ganglion explants. Our results suggest that specific selection among numerous substrates of a given ADAM is determined by ICD modification of the substrate., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Ectodomain shedding of transmembrane precursor proteins generates numerous life-essential molecules, such as epidermal growth factor receptor ligands. This cleavage not only releases the regulatory growth factor, but it is also the required first step for the subsequent processing by γ-secretase and the release of gene regulatory intracellular fragments. Signaling within the cell modifies the cytoplasmic tails of substrates, a step important in starting the specific and regulated cleavage of a large number of studied substrates. Ectodomain cleavage occurs, however, on the outside of the plasma membrane and is carried out by membrane-bound metalloproteases. How the intracellular domain modification communicates with the ectodomain of the substrate to allow for cleavage to occur is unknown. Here, we show that homodimerization of a cluster-of-differentiation-44 or of pro-neuregulin-1 monomers represents an essential pre-condition for their regulated ectodomain cleavage. Both substrates are associated with their respective metalloproteases under both basal or cleavage-stimulated conditions. These interactions only turn productive by specific intracellular signal-induced intracellular domain modifications of the substrates, which in turn regulate metalloprotease access to the substrates' ectodomain and cleavage. We propose that substrate intracellular domain modification induces a relative rotation or other positional change of the dimerization partners that allow metalloprotease cleavage in the extracellular space. Our findings fill an important gap in understanding substrate-specific inside-out signal transfer along cleaved transmembrane proteins and suggest that substrate dimerization (homo- or possibly heterodimerization) might represent a general principle in ectodomain shedding., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Unlabelled: Ectodomain cleavage (shedding) of transmembrane proteins by metalloproteases (MMP) generates numerous essential signaling molecules, but its regulation is not totally understood. CD44, a cleaved transmembrane glycoprotein, exerts both antiproliferative or tumor-promoting functions, but whether proteolysis is required for this is not certain. CD44-mediated contact inhibition and cellular proliferation are regulated by counteracting CD44 C-terminal interacting proteins, the tumor suppressor protein merlin (NF2) and ERM proteins (ezrin, radixin, moesin). We show here that activation or overexpression of constitutively active merlin or downregulation of ERMs inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced [as well as serum, hepatocyte growth factor (HGF), or platelet-derived growth factor (PDGF)] CD44 cleavage by the metalloprotease ADAM10, whereas overexpressed ERM proteins promoted cleavage. Merlin- and ERM-modulated Ras or Rac activity was not required for this function. However, latrunculin (an actin-disrupting toxin) or an ezrin mutant which is unable to link CD44 to actin, inhibited CD44 cleavage, identifying a cytoskeletal C-terminal link as essential for induced CD44 cleavage. Cellular migration, an important tumor property, depended on CD44 and its cleavage and was inhibited by merlin. These data reveal a novel function of merlin and suggest that CD44 cleavage products play a tumor-promoting role. Neuregulin, an EGF ligand released by ADAM17 from its pro-form NRG1, is predominantly involved in regulating cellular differentiation. In contrast to CD44, release of neuregulin from its pro-form was not regulated by merlin or ERM proteins. Disruption of the actin cytoskeleton however, also inhibited NRG1 cleavage. This current study presents one of the first examples of substrate-selective cleavage regulation., Implications: Investigating transmembrane protein cleavage and their regulatory pathways have provided new molecular insight into their important role in cancer formation and possible treatment., (©2015 American Association for Cancer Research.)

Background: chronic diseases are responsible for 60% of deaths and 75% of spending on public health. There are few works on the prevalence of this type of pathology in prison., Objective: Describe the prevalence of chronic major diseases in the population and the major risk factors observed., Methods: Multicenter transversal descriptive study. The sample size was 1,170 people, who were selected through sampling stratified with simple allocation by strata among 9 prisons in the country. There were interviews and physical examinations between May and June 2013. Variables were collected: socio-demographic, diagnostic, anthropometric, clinical-analytical and risk factors. A descriptive and subsequent comparative analysis was carried out using non-parametric tests for quantitative variables using the Mann-Whitney test and a Ji-square test for categorical variables. Subsequently, binary logistic regression models to evaluate the influence of factors of risk in major pathologies. The manuscript was approved by the Ethics Committee for clinical research of the University General Hospital of Castellon., Results: 1 of every 2 inmates has some type of chronic disease out of the 1,077 participated (92.1). Median age of 37.4 years IQR (30.0 to 44.8). 95 males, 40.6 foreigners. Prevalence: dyslipidemias (34.8); arterial hypertension (17.8); Diabetes (5.3); asthma (4.6); COPD (2.2); ischaemic heart disease (1.8) and (1.5) cardio-circulatory pathologies. Main risk factors: smoking, obesity, abdominal fat distribution, consumption of cocaine and age., Conclusions: It would be interesting to establish early diagnosis, encourage giving up smoking, and physical activity and dietary advice to combat the major modifiable risk factors.

White shrimp, Litopenaeus vannamei, subadults were exposed to four dilutions of the 96 h cadmium LC50 reported for postlarvae (PL12) of this species, and the effects were evaluated after 5, 48, and 96 h of exposure. While treatments did not affect survival and hemolymph clotting time increased with time, but not as a response to Cd exposure, the intensity of other responses was related to concentration, to time of exposure, and to their interaction. Hemocyanin decreased with time in all metal concentrations but increased in the control treatment, and an almost similar trend was observed with hemocyte numbers. As an initial response, phenoloxidase activity decreased with all metal concentrations, but it increased later to values similar or higher than the control treatment.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Agriculture is one of the most important economic activities in Sinaloa, Mexico. The Culiacan Valley is an extensive agricultural region characterized by a variety of crops with high-yield productions. In this study, concentrations of organochlorine (OCPs) and organophosphorus (OPs) pesticides and polychlorobiphenyls (PCBs) were determined in sediments of the agricultural drainage system of Culiacan Valley. Overall, 32 compounds were detected, with concentrations widely ranging from 0.03 to 1 294 ng g(-1) dry weight. OCP concentrations (15) ranged from 0.1 to 20.19 ng g(-1) dw. OP concentrations (8) ranged from 0.03 to 1294 ng g(-1) dw, and diazinon was the compound with the highest concentration. PCB concentrations were also determined and varied from 0.05 to 3.29 ng g(-1) dw. Other compounds detected included permethrin, triadimefon, and fipronil. The central zone registered the higher concentrations and the greatest number of compounds, which could be related to the occurrence of horticultural fields in this zone. According to sediment quality guidelines, the compounds exceeding the probable effect level were γ-HCH, p,p'-DDT and p,p'-DDE, while the pesticides above the maximum permissible concentration were endosulfan, azinphos methyl, diazinon, dichlorvos, and permethrin. Although Sinaloa is an important agricultural crop producer in northwest Mexico, there are not many studies dealing with pesticide distribution in agricultural areas.

Lung metastasectomy is an area of interest and controversy in surgical oncology. Most of the available evidence derives from small cohorts with short follow-up. The aim of this study was to evaluate the oncologic outcomes in an 18-year cohort from a single center. We retrospectively reviewed 398 patients with several malignancies who underwent lung metastasectomy between January 1990 and December 2008. Demographic, clinical, and surgical variables were evaluated. Uni- and multivariate analyses were performed to identify factors associated with overall survival (OS). Mean follow-up was 20 months. Wedge resection was performed in 297 cases and 101 required anatomic resections. In 303 patients the disease-free interval (DFI) was >6 months meanwhile 95 patients had a DFI ≤6 months. Complete resection was achieved in 351 patients (88.2%). Median OS for all patients was 81.9 months (95% CI, 36.9-126.9). On multivariate analysis, factors associated with a poor overall survival were DFI <6 months (HR, 1.74; 95% CI, 1.24-2.4; p=0.001) and incomplete resection (HR, 1.58 95% CI, 1.01-2.5; p=0.0047). Independent prognostic factors associated with better survival were DFI >6 months and complete resection. Size and number of metastases as well as re-do metastasectomy were not associated with worse survival., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The capybaras are the biggest rodents in the world but, however, there are not extensive population genetics studies on them. In the current work, we studied the genetic structure of a troop of 31 capybaras (Hydrochoerus hydrochaeris) sampled in Hato Corozal, Casanare Department at the Colombian Eastern Llanos, by means of five microsatellite markers. The gene diversity was 0.61 and the average allele number was 5.2, which is a medium-low level for markers of this nature. Out five markers employed, three were in Hardy-Weinberg equilibrium meanwhile one showed a significant homozygote excess and other presented a significant heterozygote excess. There were not significant genetic differences between males and females inside this troop. The application of different procedures to determine possible historical demographic changes (population expansions or bottlenecks) clearly showed that the population analyzed crossed over a very narrow recent bottleneck. The illegal hunt is the possibly cause of this strong genetic bottleneck.

The dinoflagellate Cochlodinium polykrikoides isolated from Bahía de La Paz, Gulf of California, showed an important short-term toxic effect on the spotted rose snapper Lutjanus guttatus. This microalga was able to decrease fish liver catalase activity and lipid peroxidation. Fish exposed to live dinoflagellates developed an abnormal mucus secretion on the gills that was directly related to algal cell concentration. Hepatic catalase inhibition and an increase in mucus secretion on the gills occurred when fish were exposed to 2 x 10(6) cells L(-1) of C. polykrikoides. Lipid peroxidation was significantly different at 4 x 10(6) cells L(-1) and the hepatosomatic index decreased at 3 x 10(6) cells L(-1). Our results suggest that oxidative stress contributes, at least in part, to the ichthyotoxic effect of C. polykrikoides from the Gulf of California.

Biomarkers have been useful tools to monitor some effects of pollution in coastal environments. Hepatic expression of heat-shock protein 70 (Hsp70) and cytochrome P450 1A (CYP1A) were analyzed in white mullet (Mugil curema) by RT-PCR from July, 2005 until July, 2006 in three coastal lagoons located in the southern Gulf of California, Mexico. These three coastal systems receive contaminants derived from local anthropogenic activities. Heat-shock proteins function to maintain protein integrity in the presence of stressors (such as heat or chemicals) and can be used as biomarkers of homeostatic alterations in polluted environments, whereas cytochrome P450 family members participate in steroid hormone synthesis and metabolism, and in xenobiotic transformation as a detoxification mechanism. The expression levels of both genes showed consistency in time and space, and presented a high overall correlation (r = 0.731, P < 0.001). Regardless of a high individual variability, both genes presented higher expression levels in the Urias Estuary (P < 0.001 and P < 0.05 for CYP1A and Hsp70, respectively), which was considered the most polluted among the three systems, especially during the rainy season (summer to fall). Gene expression levels were significantly associated with non-halogenated hydrocarbon concentrations in sediments during the sampling period (r = 0.686, P = 0.019 for CYP1A and r = 0.91, P < 0.001 for Hsp70), suggesting that both genes respond to chemicals in the environment. The results indicate that Mugil curema is a good candidate species to implement biomonitoring programs in tropical coastal environments.

Pathfinding axons change responses to guidance cues at intermediate targets. During midline crossing, spinal cord commissural axons acquire responsiveness to class 3 Semaphorins and Slits, which regulate their floor plate exit and restrict their post-crossing trajectory into a longitudinal pathway. We found that Sonic Hedgehog (Shh) could activate the repulsive response of pre-crossing axons to Semaphorins. Blocking Shh function with a monoclonal antibody to Shh, 5E1, in 'open-book' explants or by expressing a dominant-negative form of Patched-1, Ptch1(Delta loop2), or a Smoothened (Smo) shRNA construct in commissural neurons resulted in severe guidance defects, including stalling and knotting inside the floor plate, recrossing, randomized anterior-posterior projection and overshooting after crossing, reminiscent of Neuropilin-2 mutant embryos. Enhancing protein kinase A activity in pre-crossing axons diminished Shh-induced Semaphorin repulsion and caused profound midline stalling and overshooting/wandering of post-crossing axons. Therefore, a morphogen, Shh, can act as a switch of axon guidance responses.

The hemolytic activity of the dinoflagellate Cochlodinium polykrikoides from Bahía de La Paz, Gulf of California was investigated as part of the ichthyotoxic mechanism of this microalga. Two different kinds of erythrocytes, fish and human, were tested for the hemolytic assay. Since fatty acids have been associated with hemolytic activity in C. polykrikoides, the composition of fatty acids of this dinoflagellate was also analyzed. The concentration of C. polykrikoides causing 50% hemolysis (HE(50)) was 4.88 and 5.27x10(6) cellsL(-1), for fish and human erythrocytes, respectively. According to the standard curve of saponin, an equivalence between the hemolytic activity of saponin and the dinoflagellate concentration was found with 1mug saponinmL(-1) equivalent to 1x10(6) cellsL(-1) of C. polykrikoides. The polyunsaturated fatty acids: hexadecaenoic (16:0), docosahexaenoic (22:6 n3) and octadecapentaenoic (18:5 n3) were found in an abundance of approximately 62% of total fatty acids.

Background: There are no available studies assessing job satisfaction amongst nursing staff in Spanish prisons. The aim of this study is to establish overall levels of job satisfaction and determine each of the components., Method: Cross-sectional and multi-centre descriptive study conducted in Spanish prisons. A Font Roja satisfaction questionnaire adapted by J. Arranz for the study was used to measure degrees of job satisfaction using a Likert's scale. A parametric test was used and a regression model was constructed for predictive ends., Results: 376 nurses answered the questionnaire (Participation Rate 62.7%; Response Rate 76.7%) 67 centres took part (91.8%). The average satisfaction mark was 2.84 (CL 95%: 2.81-2.87). The lowest ranked components were job variety 1.66 (CL 95%: 1.58-1.74), job-related stress 2.15 (CL 95%: 2.08-2.23) and control over job 2.77 (CL 95%: 2.73-2.82). The highest ranked aspect was job satisfaction, averaging 3.52 (CL 95%: 3.44-3.58)., Conclusions: The average satisfaction mark for prison nursing staff was low when compared to other groups of health care professionals, which implies the need for corrective measures.

We selected muscle tissue from nine commercial fish species, seven teleosts and two elasmobranchs, frequently caught in the NW Mediterranean trawling grounds in two different habitats (the continental shelf at 53 m and the slope at 660 m) for cholinesterases (ChEs) characterisation and activities determination, as well as the measure of lipid peroxidation (LP) levels. Acethyl- (AChE), butyryl- (BChE) and propionyl- (PrChE) cholinesterase were chosen as exposure markers of neurotoxic chemicals/molecules and LP as an effect marker of oxidative damage. The use of diagnose inhibitors: eserine sulphate, iso-OMPA and BW284c51 confirmed the measurement of true ChEs as well as the presence of pseudocholinesterases. The present study has evidenced the existence of interspecies differences, especially between teleosts and elasmobranchs but not in relation to depth. Moreover, the good correlation observed between all ChEs in most of the studied fish, supports the use of AChE as neurotoxic marker in field pollution monitoring. The non-metric multidimensional scaling analysis identified the commercial species hake Merluccius merluccius, among teleosts, and the shark, Galeus melastomus, as more adequate sentinel species in commercial fishing grounds. AChE activity showed a relationship with the fish trophic level, while all ChEs revealed a relationship with the feeding habits (benthic, suprabenthic, pelagic) and the stomach fullness. BChE activity and LP levels were the only markers to show a relationship with their swimming capacity.

There is a lack of information on monitoring neurotoxicity in offshore commercial species. To help fill this gap, we sampled hake (Merluccius merluccius) and Norway lobster (Nephrops norvegicus) in fishing grounds off the coast of l'Ametlla de Mar (NW Mediterranean) in June 2005 at a depth of 100 m and 400 m. Additionally, at 400 m depth, two other fish species, Micromesistius poutassou and Phycis blennoides were included. Neurotoxicity markers such as Colinesterases (ChEs), namely acethyl- (AChE), butyryl- (BChE), propionyl- (PrChE) and carboxilesterase (CbE) were measured in muscle. Lipid peroxidation (LP), a marker of oxidative damage, was also included. The results are discussed in relation to the animal's sex, size and fishing depth. A comparison of esterases and LP levels between muscle and liver of hake and between muscle and hepatopancreas of Norway Lobster was made. AChE was dominant in muscle and CbE in hepatopancreas. No differences between fish species were seen for AChE. However, N. norvegicus, presented lower levels of ChEs and LP. A size-dependence in ChEs was seen for M. merluccius, with larger animals showing significantly lower activities (p<0.05). Sex-dependence was seen in N. norvegicus for most esterases, except AChE, with males displaying higher activities (p<0.05). A sampling-depth effect was also seen in the crustacea, with animals from 100 m generally presenting lower esterase activities and higher LP levels.

The toxicity of methamidophos on the shrimp Litopenaeus vannamei was evaluated using acetylcholinesterase (AChE) activity, behavior, and feeding rate as effect criteria. The biochemical characterization of the soluble cholunesterase (ChE) present in both muscle and eye tissues of L. vannamei was performed in a first phase of the study. In both tissues, almost full inhibition of enzyme activity by eserine sulfate was found, indicating that the measured activity is mainly from ChE and not from other esterases. The highest rate of substrate hydrolysis was found when acetylthiocholine was used as substrate. To evaluate the effects of methamidophos on L. vannamei AChE, behavior, and feeding rate, shrimps were exposed for 24h to several sublethal concentrations of methamidophos. Significant effects of the pesticide on behavior and AChE were found, with behavior being a more sensitive endpoint than AChE inhibition. Feeding rate was not a sensible endpoint under conditions tested.

The relationship between parasites and environmental stress were studied in two tropical coastal lagoons of Northwest Mexico: Urias estuary (highly polluted) and Teacapan estuary (slightly polluted). Metazoan parasites were examined in 292 white mullet (Mugil curema) specimens collected bimonthly during a year from both systems. Haliotrema mugilinus, Metamicrocotyla macracantha, Ergasilus sp., Caligus sp., Holobomolochus sp., and Lernaeopodidae were found in gills, while Contracaecum sp. larvae III was found liver, hepatic portal vein and kidneys. Ecological indices were influenced by the slightly higher number of parasitic species in Urias compared to Teacapan, as well as the clear dominance of two species: Ergasilus sp. and Contracaecum sp. in both systems. In fact, Ergasilus sp. showed considerably higher abundance in Urias, possibly indicating that its success was a result of adverse conditions affecting the host, while Contracaecum sp showed higher abundances in Teacapan, suggesting that the environmental conditions occurring in Urias could have produced negative impacts on the nematode's infective potential.

Sand gobies, Pomatoschistus minutus, were collected monthly from September 2002 to August 2003 at a station situated 8 km upstream from the mouth of the Guadalquivir estuary (southwest Spain). Physical parameters of the water and selected biomarkers of organic pollution were recorded in the fish to discuss its potential as a sentinel species in estuaries. The biomarkers selected were the activities of catalase (CAT), 7-ethoxyresorufin-O-deethylase (EROD), and glutathione S-transferase (GST) in the liver and acetylcholinesterase (AChE) and lipid peroxidation (LP) in the head. The results showed an increase in total protein synthesis in late spring and early summer coinciding with the reproductive period as well as the release of fresh water from a dam situated 110 km upstream. During the same period, a significant depletion of hepatic GST and head AChE but higher LP levels in this tissue suggest exposure to pesticides such as those applied to crops established along the course of the river and reaching the estuary mostly when the freshwater discharges occur. Changes in CAT and EROD activities fluctuated randomly and were not noted as seasonally dependent. Biomarker fluctuations in sand goby are discussed as normal seasonal variations, but other variables-such as potential local pollution inputs-cannot be disregarded.

The causes of disease in cultured shrimp are difficult to ascertain but there is evidence that disease is correlated with environmental factors. Crustaceans are particularly sensitive to insecticides due to their close phylogenetic relationship with insects. The objective of this study was to investigate whether there was an increased susceptibility of the shrimp Litopenaeus vannamei to Vibrio parahaemolyticus, when exposed to methyl parathion. The outline of the study was the following: An LC50 96 h was determined to methyl parathion orally offered to juvenile shrimp. Further experiments were carried out in order to determine a concentration that affected the shrimp (verified by measuring the acethylcholinesterase activity) while producing minimal mortalities. This sublethal concentration was used in a susceptibility experiment where methyl parathion was offered to shrimp which were later injected with V. parahaemolyticus in a dose expected to kill less than 15%. Probit analysis estimated a 96 h median lethal concentration (LC50) of 1.56 microg g(-1). Mortality and AChE activity showed a concentration-response relationship in the exposure treatments. The median inhibitory concentration (IC50) determined was 0.029 microg g(-1). These results suggested that a concentration of 0.1 microg g(-1) was appropriate for the bacteria-pesticide interaction test as it was able to elicit 11.1% mortality after 10 days of exposure, while producing an AChE inhibition of 57.12%. Cumulative mortalities were significantly increased (P<0.01) in the treatment that combined exposure to methyl parathion and V. parahaemolyticus (35.19%) in comparison with methyl parathion or V. parahaemolyticus alone (9.26% and 7.41%, respectively).