Homoeostasis between the GTPase Spg1p and its GAP in the regulation of cytokinesis in S. pombe

Cytokinesis in Schizosaccharomyces pombe begins at mitotic entry, when the site of division is defined by formation of the contractile acto-myosin ring (CAR) at the cell cortex. Contraction of the CAR and formation of the division septum are triggered at the end of mitosis by septation initiation network (SIN) proteins associated with the spindle pole body (SPB). SIN signalling requires activation of the GTPase Spg1p, which is regulated by the bipartite GTPase-activating protein (GAP) Byr4p-Cdc16p. We show that, for Spg1p to associate with the SPB, it must be bound to its GAP or to its mitotic effector, the protein kinase Cdc7p. Analysis of the GAP proteins reveals that the steady-state level of Byr4p reflects that of Spg1p. Furthermore, if the interaction of Byr4p with Spg1p is compromised, the level of Byr4p decreases dramatically. The adaptation of the level of Byr4p to that of Spg1p requires the presence of Cdc16p and is mediated by proteasome-dependent destruction. It requires neither association with the SPB nor an active SIN. We propose a mechanism that limits the amount of the Byr4p-Cdc16p GAP to the amount required to inhibit Spg1p signalling

Controller therapy for asthma: montelukast versus fluticasone

Introducción: El asma es un trastorno inflamatorio crónico de las vías aéreas. Esta inflamación genera un aumento asociado de la hiperreactividad de las vías aéreas a una variedad de estímulos y una limitación del flujo aéreo. El tratamiento controlador del asma tiene como objetivos lograr y mantener control de los síntomas, prevenir las exacerbaciones, mantener la función pulmonar lo mas cerca posible a la normalidad, evitar efectos adversos de la medicación, prevenir obstrucción irreversible de la vía aérea y disminuir la mortalidad. Los medicamentos utilizados para este fin son los antinflamatorios dentro de los cuales se incluyen los grupos de corticoesteroides, cromonas y antileucotrienos. Objetivo: El objetivo de esta revisión bibliográfica es indicar las evidencias encontradas sobre mayor efectividad en este cuadro clínico entre Fluticasona y Montelukast. Material y métodos: Se realizó una revisión bibliográfica, en la cual se utilizo para la búsqueda de información las bases de datos PUBMED, MEDLINE y BIBLIOTECA VIRTUAL DE SALUD artículos científicos publicados en los últimos 5 años que comparan el tratamientote ambos fármacos. Conclusión: El fármaco más efectivo como monoterapia para el tratamiento controlador del asma en niños es la fluticasona frente al montelukast, por lo que esta es considerada la terapia de primera línea.Introduction: Asthma is a chronic inflammatory disorder of the airways. This inflammation is an associated increase in Nonspecific hyperresponsiveness airway to a variety of stimuli and airflow limitation. The asthma controller therapy aims to achieve and maintain control of symptoms, prevent exacerbations, maintaining lung function as close as possible to normal, avoid adverse effects of medication, prevent irreversible obstruction of the airway and reduce mortality . Medicines used for this purpose are the anti-inflammatory within which groups include corticosteroids, chromones and leukotriene. Objective: Fluticasone (inhaled corticosteroid) and montelukast (antileukotriene) are commonly used drugs for the treatment of pediatric asthma controller so that the objective of this review is to summarize the evidence on which of the two showed greater effectiveness in the treatment. Methods: A literature review, which was used to search for information databases PUBMED, MEDLINE and HEALTH LIBRARY scientific articles published over the past 5 years, comparing treatment with fluticasone and montelukast. Conclusion: The most effective drug as monotherapy for asthma controller therapy in children is fluticasone compared with montelukast, so this is considered first-line therapy.Fil: Acevedo, Maria E..Fil: Cano, Alejandra A..Fil: Lopez, Vanina A..Fil: Viola, Luciana S..Fil: Gerometta, Rosana María del Rosario. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Analysis of S. pombe SIN protein association to the SPB reveals two genetically separable states of the SIN.

The Schizosaccharomyces pombe septation initiation network (SIN) regulates cytokinesis, and asymmetric association of SIN proteins with the mitotic spindle pole bodies (SPBs) is important for its regulation. Here, we have used semi-automated image analysis to study SIN proteins in large numbers of wild-type and mutant cells. Our principal conclusions are: first, that the association of Cdc7p with the SPBs in early mitosis is frequently asymmetric, with a bias in favour of the new SPB; second, that the early association of Cdc7p-GFP to the SPB depends on Plo1p but not Spg1p, and is unaffected by mutations that influence its asymmetry in anaphase; third, that Cdc7p asymmetry in anaphase B is delayed by Pom1p and by activation of the spindle assembly checkpoint, and is promoted by Rad24p; and fourth, that the length of the spindle, expressed as a fraction of the length of the cell, at which Cdc7p becomes asymmetric is similar in cells dividing at different sizes. These data reveal that multiple regulatory mechanisms control the SIN in mitosis and lead us to propose a two-state model to describe the SIN

Giyera sa Droga (War on Drugs): An application of the Theory of Planned Behaviour to the influence of negative word-of-mouth communication to the tourists’ intention to visit the Philippines

War on drugs campaign commenced in the Duterte Administration in 2016. The campaign resulted to worldwide criticisms which spread negative word-of-mouth about the Philippines. The study applied the Theory of Planned Behaviour (TPB) by Ajzen and Fishbein (1991) to test the negative word-of-mouth (WOM) communication regarding war on drugs to tourists’ intention to visit the Philippines. Structural Equation Modelling was utilized to determine the relationship among the three factors of TPB namely, Attitude, Subjective Norm, and Perceived Behavioural Control to tourist intention. The data was collected from 242 foreign passport holders and through an interview conducted with the Department of Tourism (DOT). The result of the study reveals that Attitude does not affect tourist intention to travel. On the other hand, Subjective Norm has the strongest influence on tourist intention followed by Perceived Behavioural Control but does not necessarily affect their decision-making behaviour towards visiting the Philippines regardless of the campaign

Evaluando el progreso de la eficiencia con tecnología en una cadena de hoteles española

This paper analyzes the changes in the total factor productivity index of a Spanish hotel chain in the period from 2007 to 2010 with the purpose of identifying efficiency patterns for the chain in a period of financial crisis. The data envelopment analysis (DEA) Malmquist productivity index was used to estimate productivity change in 38 hotels of the AC chain. Results reveal AC hotels’ efficiency trends and, therefore, their competitiveness in the recession period; they also show the changes experienced in these hotels’ total productivity and its components: technological and efficiency changes. Positive efficiency changes were due to positive technical efficiency rather than technological efficiency. The recession period certainly influenced the performance of AC Hotels, which focused on organizational changes rather than investing in technology.Este artigo analisa as mudanças no fator total de produtividade de uma cadeia de hotéis na Espanha, no período de 2007-2010, com o propósito de identificar os padrões da cadeia em um período de crise financeira. O índice data envelopment analysis (DEA) Malmquist de produtividade foi usado para estimar a mudança da produtividade nos 38 hotéis da AC Cadeia de Hotéis. Os resultados revelaram as tendências de eficiência e competitividade da AC Hotéis em um período de recessão, bem como as mudanças vivenciadas na produtividade total e, consequentemente, em seus componentes de eficiência e tecnológicos. O período de recessão influenciou, sem dúvida, o comportamento da AC Hotéis, que buscou mais mudanças organizacionais do que tecnológicas.Este artículo analiza los cambios del índice de productividad del factor total de una cadena de hoteles españoles en el periodo de 2007 hasta 2010, con el propósito de identificar patrones de eficiencia para la cadena en un periodo de crisis financiera. El índice de productividad data envelopment analysis (DEA) Malmquist fue utilizado para estimar el cambio de productividad en 38 hoteles de la cadena AC. Los resultados revelan las tendencias de la eficiencia de los hoteles AC y, por lo tanto, su competitividad en el periodo de recisión; ellos también demuestran los cambios experimentados en la productividad total de eses hoteles y sus componentes: cambios de eficiencia y tecnológicos. Cambios de eficiencia positivos se debieron más bien a eficiencias técnicas positivas que a eficiencias tecnológicas. El periodo de recesión ciertamente ha influenciado los Hoteles AC, que enfocaron más en los cambios organizacionales que en invirtiendo en tecnología

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication