Complementary training in disasters for healthcare professionals: an analysis of the official offer in brazil and mexico / Formación complementaria en desastres para profesionales de la salud: un análisis de la oferta oficial en brasil y méxico / Formação complementar em desastres para profissionais da saúde: uma análise da oferta oficial no brasil e méxico

ABSTRACT Objective: to identify courses available online by national civil defense bodies in Brazil and Mexico to assist in the additional training of healthcare professionals for disasters. Method: an exploratory descriptive study, based on a qualitative approach, using technological prospecting methodology, carried out on the official Civil Defense websites in Brazil and Mexico. Results: ten courses offered by the Government of Mexico's National Center for Disaster Prevention were found, nine of which were short-term and one offered as vocational training. All of these courses were synchronous. In Brazil, 36 courses were located, all in asynchronous formats, with durations varying between 20 and 50 hours. Although the courses presented programmatic content that included activities inherent to healthcare professionals, none of them made specific mention of professionals in this area as the target audience. Conclusion: the prospective study reinforces that Information and Communication Technologies for distance education present themselves as an alternative present in both countries in terms of additional training for disasters, although not yet specifically aimed at healthcare professionals. The need to include this area of interdisciplinary and multi-professional content reflects gaps in sector integration.

RESUMEN Objetivo: identificar cursos disponibles en línea por los organismos nacionales de defensa civil en Brasil y México para ayudar en la capacitación adicional de profesionales de la salud para desastres. Método: estudio descriptivo exploratorio, de enfoque cualitativo, utilizando metodología de prospección tecnológica, realizado en los sitios web oficiales de la Defensa Civil de Brasil y México. Resultados: se encontraron 10 cursos ofrecidos por el Centro Nacional para la Prevención de Desastres del Gobierno de México, nueve de los cuales fueron de corta duración y uno se ofreció como formación vocacional. Todos estos cursos fueron sincrónicos. En Brasil se ubicaron 36 cursos, todos en formato asincrónico, con duraciones que variaron entre 20 y 50 horas. Aunque los cursos presentaron contenidos programáticos que incluyeron actividades inherentes a los profesionales de la salud, ninguno de ellos hizo mención específica a los profesionales de esa área como público objetivo. Conclusión: el estudio prospectivo refuerza que las Tecnologías de la Información y las Comunicaciones para la educación a distancia se presentan como una alternativa presente en ambos países en términos de capacitación adicional para desastres, aunque aún no dirigida específicamente a los profesionales de la salud. La necesidad de incluir esta área de contenidos interdisciplinarios y multiprofesionales refleja brechas en la integración del sector.

RESUMO Objetivo: identificar cursos disponíveis on-line pelos órgãos de defesa civil nacional do Brasil e do México visando auxiliar na formação complementar de profissionais de saúde para desastres. Método: estudo descritivo exploratório, a partir de uma abordagem qualitativa, utilizando a metodologia de prospecção tecnológica, realizada nos sites oficiais de Defesa Civil do Brasil e do México. Resultados: foram encontrados 10 cursos oferecidos pelo Centro Nacional de Prevenção de Desastres do Governo do México, sendo nove de curta duração e um oferecido como curso técnico. Todos esses cursos na modalidade síncrona. No Brasil, localizaram-se 36 cursos, todos em formatos assíncronos, com duração variável entre 20 e 50 horas. Embora os cursos apresentassem conteúdo programático que incluía atividades inerentes aos profissionais de saúde, nenhum deles fazia menção específica aos profissionais desta área como público-alvo. Conclusão: o estudo prospectivo reforça que as Tecnologias da Informação e da Comunicação para educação a distância se apresentam como uma alternativa presente em ambos os países quanto à formação complementar para desastres, porém, ainda não direcionados especificamente aos profissionais da saúde. A necessidade de inclusão desta área de conteúdos interdisciplinares e multiprofissionais reflete lacunas de integração de setores.

Trajectories of Cancer Care in Latin America: A Scope Review: Trayectorias de atención al cáncer en América Latina. Una revisión de alcance.

OBJECTIVES: In recent decades there has been a development of research on cancer care trajectories in Latin America; however, the diversity of theoretical-methodological uses of this approach can be confusing and difficult for the academic and professional community to use. To analyze studies that have been carried out in Latin America on cancer care trajectories to propose a typology of the approaches developed and synthesize key findings. METHODS: A scope review of studies published in journals indexed in PubMed, LILACS, and SciELO databases in the period 2006-2021 was conducted. RESULTS: 22 articles were analyzed. A typology of descriptive, evaluative, and interpretative approaches was proposed. From the key findings, the following were identified: the importance of pleasure and the feeling of power in the development of risky practices; the role of popular explanatory models for the identification of abnormality and the search for attention; the interaction of various personal, interpersonal, organizational, and structural barriers that limited timely diagnosis and continuity of treatment; the sequential or parallel use of different forms of care, public and private; and the importance of social support networks. CONCLUSIONS: The proposed typology clarifies the different uses of the approach. The informative synthesis evidences problematic knots regarding multiple barriers to access and allows us to propose as priorities in future research the study of types of cancer, stages, and populations that have been scarcely addressed, as well as the diversification of methodological approaches.

Common mental disorders in the perinatal period in Primary Healthcarein Latin America: A Systematic review and meta-analysis

Existe un riesgo estadísticamente mayor de desarrollar comorbilidades mentales en el período perinatal. Existe un vacío científico en el análisis de la ocurrencia de problemas de salud mental en el período perinatal entre países de ingresos medios y bajos en el contexto de la Atención Primaria de Salud. Así, el objetivo de este estudio fue revisar la ocurrencia de trastornos mentales comunes en el período perinatal en la Atención Primaria de Salud en América Latina. Se identificó una estimación global del 37 % (IC 95 %: 32 %-43 %) de trastornos mentales comunes durante todo el período perinatal. A pesar de las altas frecuencias identificadas para los síntomas de comorbilidad mental, no hubo estudios en otros países de América Latina con excepción de Brasil, lo que impide un análisis sobre la salud mental de las mujeres latinas en el período perinatal[AU]

Existe um risco estatisticamente maior de desenvolver comorbidades mentais no período perinatal. Existe uma lacuna científica na análise da ocorrência de problemas de saúde mental no período perinatal entre famílias de média e baixa renda países no contexto da Atenção Primária à Saúde. Assim, o objetivo deste estudo foi revisar a ocorrência de transtornos mentais comuns no período perinatal em Atenção Primária à Saúde na América Latina. Uma estimativa geral de 37% (95% CI:32%-43%) de transtornos mentais comuns foram identificados durante todo o período perinatal período. Apesar das altas frequências identificadas para sintomas de comorbidade mental, não houve estudos em outros países latino-americanos com exceção de Brasil, impossibilitando uma análise sobre a saúde mental das mulheres latinas no período perinatal[AU]

There is a statistically higher risk for developing mental comorbidities in the perinatal period. There is a scientific gap in the analysis of the occurrence of mental health problems in the perinatal period among middle and low-income countries in the context of Primary Healthcare. Thus, the objective of this study was to review the occurrence of common mental disorders in the perinatal period in Primary Healthcare in Latin America. An overall estimate of 37% (95%CI: 32%-43%) of common mental disorders was identified for the entire perinatal period. Despite the high frequencies identified for mental comorbidity symptoms, there were no studies in other Latin American countries with the exception of Brazil, preventing an analysis on the mental health of Latino women in the perinatal period[AU]

Acanthamoeba castellanii Genotype T4: Inhibition of Proteases Activity and Cytopathic Effect by Bovine Apo-Lactoferrin.

Acanthamoeba castellanii genotype T4 is a clinically significant free-living amoeba that causes granulomatous amoebic encephalitis and amoebic keratitis in human beings. During the initial stages of infection, trophozoites interact with various host immune responses, such as lactoferrin (Lf), in the corneal epithelium, nasal mucosa, and blood. Lf plays an important role in the elimination of pathogenic microorganisms, and evasion of the innate immune response is crucial in the colonization process. In this study, we describe the resistance of A. castellanii to the microbicidal effect of bovine apo-lactoferrin (apo-bLf) at different concentrations (25, 50, 100, and 500 µM). Acanthamoeba castellanii trophozoites incubated with apo-bLf at 500 µM for 12 h maintained 98% viability. Interestingly, despite this lack of effect on viability, our results showed that the apo-bLf inhibited the cytopathic effect of A. castellanii in MDCK cells culture, and analysis of amoebic proteases by zymography showed significant inhibition of cysteine and serine proteases by interaction with the apo-bLf. From these results, we conclude that bovine apo-Lf influences the activity of A. castellanii secretion proteases, which in turn decreases amoebic cytopathic activity.

Rate of methicillin-resistant Staphylococcus aureus in pediatric emergency departments in Spain.

INTRODUCTION: Staphylococcus aureus is a common germ in bacterial infections in children. The rate of methicillin-resistant S. aureus (MRSA) is increasing lately. OBJECTIVES: The main aim is to know the rate of positive cultures to MRSA in Spanish pediatric emergency departments. The secondary aims are to analyse the risk factors for MRSA isolation (patient origin, history of hospitalization or surgery in the previous 90 days, antibiotherapy in the previous 60 days, presence of comorbidity, invasive devices, prior MRSA isolation) and to analyse the morbidity of these infections. METHODOLOGY: Retrospective multicenter study (07/01/2017-06/30/2018) with review of patient histories with isolation of S. aureus in samples of any origin obtained in 8 pediatric emergency departments of the Infectious Diseases Working Group of the Spanish Society of pediatric Emergencies. RESULTS: During this period, S. aureus was detected in 403 patients (average age 75.8 ± 59.2 months; 54.8% male): 28.8% hospital-related infections (HRI) and 71.2% community-related infections (CRI). Overall, MRSA rate was 16.6% (95% CI: 13-20.2%); 18.1% in HRI and 16.2% in CRI (p > 0.05). The highest rates of MRSA were obtained in skin abscesses (29.3%, CI 95%: 21.8-36.8%), patients not born in Spain (52%; CI 95%: 32-72%) or patients with a previous MRSA infection (90%; CI 95% 71.4-100%). 167 (41%) patients were admitted, 12 (3%) had complications and 4 (1%) suffered sequels. There were no deaths. CONCLUSIONS: The overall MRSA rate was one in 6 staphylococcal infections. Higher MRSA rates were detected in samples of suppurating skin injuries and in foreign children or in children with a history of previous MRSA infection. In suppurative skin lesions, early drainage is essential and the change to an antibiotic with MRSA coverage should be considered if the evolution is inadequate.

Associations between COVID-19 testing status, non-communicable diseases and HIV status among residents of sub-Saharan Africa during the first wave of the pandemic.

BACKGROUND: This study determined if non-communicable disease status, HIV status, COVID-19 status and co-habiting were associated with COVID-19 test status in sub-Saharan Africa. METHODS: Data of 5945 respondents age 18-years-old and above from 31 countries in sub-Saharan Africa collected through an online survey conducted between June and December 2020, were extracted. The dependent variable was COVID-19 status (testing positive for COVID-19 and having symptoms of COVID-19 but not getting tested). The independent variables were non-communicable disease status (hypertension, diabetes, cancer, heart conditions, respiratory conditions, depression), HIV positive status, COVID-19 status (knowing a close friend who tested positive for COVID-19 and someone who died from COVID-19) and co-habiting (yes/no). Two binary logistic regression models developed to determine associations between the dependent and independent variables were adjusted for age, sex, employment, sub region and educational status. RESULTS: Having a close friend who tested positive for COVID-19 (AOR:6.747), knowing someone who died from COVID-19 infection (AOR:1.732), and living with other people (AOR:1.512) were significantly associated with higher odds of testing positive for COVID-19 infection, while living with HIV was associated with significantly lower odds of testing positive for COVID-19 infection (AOR:0.284). Also, respondents with respiratory conditions (AOR:2.487), self-reported depression (AOR:1.901), those who had a close friend who tested positive for COVID-19 infection (AOR:2.562) and who knew someone who died from COVID-19 infection (AOR:1.811) had significantly higher odds of having symptoms of COVID-19 infection but not getting tested. CONCLUSION: Non-communicable diseases seem not to increase the risk for COVID-19 positive test while cohabiting seems to reduce this risk. The likelihood that those who know someone who tested positive to or who died from COVID-19 not getting tested when symptomatic suggests there is poor contact tracing in the region. People with respiratory conditions and depression need support to get tested for COVID-19.

[Rate of methicillin-resistant Staphylococcus aureus in pediatric emergency departments in Spain]. / Tasa de Staphylococcus aureus resistentes a meticilina en urgencias pediátricas en España.

INTRODUCTION: Staphylococcusaureus (S. aureus) is a common germ present in bacterial infections in children. Lately, the rate of methicillin-resistant S. aureus (MRSA) is increasing. OBJECTIVES: The main aim of this study is to know the rate of positive cultures to MRSA in Spanish pediatric emergency departments. The secondary aims are to analyze the risk factors for MRSA isolation (patient origin, history of hospitalization or surgery in the previous 90 days, antibiotherapy in the previous 60 days, presence of comorbidity, invasive devices, prior MRSA isolation) and to analyze the morbidity of these infections. METHODOLOGY: Retrospective multicenter study (07/01/2017-06/30/2018) with review of patient histories with isolation of S. aureus in samples of any origin obtained in 8 pediatric emergency departments of the Infectious Diseases Working Group of the Spanish Society of Pediatric Emergencies. RESULTS: During this period, S. aureus was detected in 403 patients (average age 75.8±59.2 months; 54.8% male): 28.8% hospital-related infections and 71.2% community-related infections. Overall, MRSA rate was 16.6% (95% CI: 13-20.2%); 18.1% in hospital-related infections and 16.2% in community-related infections (P>.05). The highest rates of MRSA were obtained in skin abscesses (29.3%, 95% CI: 21.8-36.8%), patients not born in Spain (52%; 95% CI: 32-72%) or patients with a previous MRSA infection (90%; 95% CI: 71.4-100%). 167 (41%) patients were admitted, 12 (3%) had complications and 4 (1%) suffered sequels. There were no deaths. CONCLUSIONS: The overall MRSA rate was one in six staphylococcal infections. Higher MRSA rates were detected in samples of suppurating skin injuries and in foreign children or in children with a history of previous MRSA infection. In suppurative skin lesions, early drainage is essential and the change to an antibiotic with MRSA coverage should be considered if the evolution is inadequate.

Conversion of RNA Aptamer into Modified DNA Aptamers Provides for Prolonged Stability and Enhanced Antitumor Activity.

Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in in vitro experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers in vivo by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.

La prensa y la participación social frente a los desastres: desde el sismo de Oaxaca de 1787 al sismo de Tehuantepec de 2017 / A Imprensa E A Participação Social Diante Dos Desastres: Do Terremoto De Oaxaca De 1787 Ao Terremoto De Tehuantepec Em 2017 / The Press And Social Participation In The Face Of Disasters: From The Oaxaca Earthquake Of 1787 To The Tehuantepec Earthquake Of 2017

A través de su historia, México se ha caracterizado por ser un país vulnerable a la ocurrencia de diversos eventos de origen meteorológico y geofísico debido a su ubicación geográfica.

The press and social participation in the face of disasters: from the Oaxaca earthquake of 1787 to the Tehuantepec earthquake of 2017.

A imprensa e a participação social diante dos desastres: do terremoto de Oaxaca de 1787 ao terremoto de Tehuantepec em 2017.

Underutilization of the reports of adverse events in an Argentine hospital.

BACKGROUND: An adverse event is defined as any unintentional harm that results in temporary or permanent disability and/or prolongation of hospitalization time, or death of a patient; as a consequence of health care provided by any staff member of the health institution. OBJECTIVES: The aim was to describe the adverse events that affect patient safety, reported in 2015 in a private hospital in the city of Córdoba, Argentina. METHODS: We analyzed 678 events reported through the computer system on the hospital's intranet. RESULTS: The highest frequency of events reported corresponded to the nursing professionals (40.7% ). Problems related to drug therapy process showed the highest frequency of reports (17.7% ), followed by communication failures (11.1% ) and patient's fall (10.3% ). In the notification of the causes of the incident, 51.9% of "No answer" was observed. CONCLUSION: In the case of this hospital, this valuable tool is being underutilized. The reports should allow identifying the entire chain of events that lead to the incidents to address effective interventions in patient safety that involve all hospital staff, with greater emphasis on senior staff.

Mild hypothermia upregulates myc and xbp1s expression and improves anti-TNFα production in CHO cells.

Chinese hamster ovary (CHO) cells are the most frequently used host for commercial production of therapeutic proteins. However, their low protein productivity in culture is the main hurdle to overcome. Mild hypothermia has been established as an effective strategy to enhance protein specific productivity, although the causes of such improvement still remain unclear. The self-regulation of global transcriptional regulatory factors, such as Myc and XBP1s, seems to be involved in increased the recombinant protein production at low temperature. This study evaluated the impact of low temperature in CHO cell cultures on myc and xbp1s expression and their effects on culture performance and cell metabolism. Two anti-TNFα producing CHO cell lines were selected considering two distinct phenotypes: i.e. maximum cell growth, (CN1) and maximum specific anti-TNFα production (CN2), and cultured at 37, 33 and 31°C in a batch system. Low temperature led to an increase in the cell viability, the expression of the recombinant anti-TNFα and the production of anti-TNFα both in CN1 and CN2. The higher production of anti-TNFα in CN2 was mainly associated with the large expression of anti-TNFα. Under mild hypothermia myc and xbp1s expression levels were directly correlated to the maximal viable cell density and the specific anti-TNFα productivity, respectively. Moreover, cells showed a simultaneous metabolic shift from production to consumption of lactate and from consumption to production of glutamine, which were exacerbated by reducing culture temperature and coincided with the increased anti-TNFα production. Our current results provide new insights of the regulation of myc and xbp1s in CHO cells at low temperature, and suggest that the presence and magnitude of the metabolic shift might be a relevant metabolic marker of productive cell line.

Desastres en México de 1900 a 2016: patrones de ocurrencia, población afectada y daños económicos / Disasters in Mexico, 1900-2016: Patterns of occurrence, population affected, and economic damages / Desastres no México de 1900 a 2016: padrão de ocorrência, população atingida e prejuízos econômicos

RESUMEN Objetivo Caracterizar los patrones de ocurrencia de desastres, defunciones, población afectada y daños económicos en México en el período 1900-2016. Métodos Se realizó un estudio descriptivo de las frecuencias de desastres, de defunciones y de personas afectadas y se estimaron los daños económicos para México en el período señalado. Se utilizó la base de datos EM-DAT del International Disaster Database, del Centre de Recherche sur l'Epidémiologie des Désastres de L'École de Santé Publique de l'Université Catholique de Louvain, Belgique. Resultados Se observó un aumento de la frecuencia de desastres a partir de la década de los noventa. Los patrones de ocurrencia de desastres en México indican que el porcentaje más alto es el de los de origen meteorológico e hidrológico (tormentas, temperaturas extremas, inundaciones, aludes y acción de los oleajes), que representan la mitad de los desastres registrados. El pocentaje de los desastres de origen meteorológico, hidrológico y climatológico oscila entre 50%-60% y son los que han provocado mayores daños a México en la serie analizada. Los que más defunciones han causado son los geofísicos, seguidos de los hidrológicos y los meteorológicos. El costo de los daños asciende con el paso de las décadas. Conclusiones De los 219 desastres analizados en el período mencionado, 63,4% se ha registrado a partir de 1990. La frecuencia de los desastres y las necesidades de inversión en su prevnción y mitigación van en aumento.

ABSTRACT Objective Characterize the patterns in the occurrence of disasters, associated deaths, population affected, and economic damages in Mexico over the period 1900-2016. Methods In a descriptive study approach, information was gathered on the frequency of disasters, associated deaths, persons affected, and economic damages in Mexico over the period indicated, using the International Disaster Database (EM-DAT) of the Center for Disaster Epidemiology Research (CRED) of the School of Public Health, Catholic University of Louvain, Belgium. Results In Mexico, an increase was observed in the frequency of disasters starting in the 1990s. According to the pattern of occurrence, the highest percentage were of hydrometeorological origin (storms, extreme temperatures, floods, avalanches, and storm surges), which accounted for half the reported disasters. In the series analyzed, disasters of hydrologic, meteorological, or climatological origin represented between 50% and 60% of the events and were the ones that caused the greatest damage. Geophysical events caused the most deaths, followed by hydrologic and then by meteorological events. The cost of damages increased with each decade. Conclusions Of the 219 disasters analyzed over the period, 63.4% have occurred since 1990. The frequency of the disasters and the need for investment in their prevention and mitigation are increasing.

RESUMO Objetivo Caracterizar o padrão de ocorrência de desastres, mortes, população atingida e prejuízos econômicos no México no período 1900-2016. Métodos Foi realizado um estudo descritivo da frequência de desastres, mortes e população atingida no México sendo estimados os prejuízos económicos no período considerado. Foi usada a base de dados EM-DAT do International Disaster Database do Centro de Pesquisa Epidemiológica de Desastres da Escola de Saúde Pública da Université Catholique de Louvain, Bélgica. Resultados Foi observado um aumento da frequência de desastres a partir da década de 1990. Os padrões de ocorrência de desastres no México demonstram uma maior porcentagem de desastres de origem meteorológica e hidrológica (temporais, temperaturas extremas, enchentes, deslizamentos e ação das ondas), representando metade das ocorrências registradas. A porcentagem de desastres de origem meteorológica, hidrológica e climatológica variou entre 50% e 60% e foram os desastres que causaram maior prejuízo ao país na série analisada. Os desastres que causaram mais mortes foram os geofísicos, seguidos dos hidrológicos e meteorológicos. O montante do prejuízo económico aumentou ao longo dos anos. Conclusões Dos 219 desastres analisados no período considerado, 63,4% foram registrados a partir de 1990. A frequência dos desastres está aumentando assim como a necessidade de investimento em prevenção e redução dos danos.

STAT3 inhibition by STA21 increases cell surface expression of MICB and the release of soluble MICB by gastric adenocarcinoma cells.

NKG2D is an activating receptor expressed on NK cells that binds to a variety of ligands, including MICA and MICB. These cell surface glycoproteins are overexpressed under cellular transformation, thus playing an important role in cell-mediated immune response to tumors. STAT3 is a transcription factor that is constitutively active in cancer. It negatively regulates MICA expression on target cells, while its inhibition enhances NK cell cytotoxicity against tumors. In this work, we aimed to describe the effect of STAT3 signaling inhibition by STA21 on the regulation of MICB expression in gastric adenocarcinoma cells and its effect on the cytotoxic function of NK cells. Treatment of gastric adenocarcinoma cells with STA21 induced an increase in MICB expression and soluble MICB secretion, as well as a variable pattern on effector cell degranulation. Soluble MICB secretion by gastric adenocarcinoma cells was not affected by metalloprotease inhibition. We also observed that primary gastric adenocarcinoma tissue released soluble MICB into the extracellular milieu. Recombinant MICB induced a significant decrease in the levels of NKG2D receptor on effector NK and CD8+ T cells, which correlated with an impaired cytotoxic function. Altogether, our data provide evidence that STAT3 signaling pathway regulates MICB expression on gastric adenocarcinoma cells and that recombinant soluble MICB compromises the cytolytic activity of NK cells.

Evaluación neuropsicológica en niños y adolescentes con fenilcetonuria e hiperfenilalaninemia y su relación con los niveles de fenilalanina plasmática / Neuropsychological assessment among children and adolescents with phenylketonuria and hyperphenylalaninemia and its relationship with plasma phenylalanine levels

Aunque, con tratamiento precoz, los pacientes con fenilcetonuria pueden presentar niveles de inteligencia normales, es importante optimizar el control dietético para mantener niveles de fenilalanina adecuados y poder desarrollar su potencial intelectual sin alteraciones en sus tareas diarias por déficits en las funciones ejecutivas. Se presenta una serie de 26 pacientes, diagnosticados y tratados precozmente, a quienes se realizó una evaluación psicométrica junto con determinaciones de fenilalanina a lo largo de su vida y en el momento de realización de los tests. Se observa una tendencia a la relación inversa entre el cociente intelectual y la fenilalanina concurrente, la mediana de fenilalanina y el cociente fenilalanina/tirosina, así como una tendencia a la relación negativa entre las funciones ejecutivas y los valores de fenilalanina concurrentes y durante la vida.

Although with early treatment phenylketonuria patients may have average intelligence levels, it is important to optimize the nutritional management to maintain adequate phenylalanine levels, so that patients can develop their intellectual potential free of abnormalities in their daily activities due to deficits of cognitive executive functions. This study presents a series of 26 patients, diagnosed and treated early, who underwent a psychometric evaluation together with phenylalanine determinations along their lives, and at the time of doing the tests. A trend is observed towards a reverse relationship between IQ and concurrent phenylalanine concentration, phenylalanine median and phenylalanine/tyrosine ratio. Likewise, a trend towards a negative relationship is observed between executive functions and concurrent phenylalanine values along patients' lives.

Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients.

Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

Application of Pediatric Appendicitis Score on the emergency department of a secondary level hospital.

BACKGROUND: Acute appendicitis is the most common surgical emergency during childhood. Accurate early diagnosis is important to avoid complications and unnecessary interventions. In 2002, Samuel developed the Pediatric Appendicitis Score (PAS) based on a series of data obtained from anamnesis, physical examination, and laboratory tests. The main purpose of this study was to check the validity of PAS and its applicability to our population. METHODS: Prospective observational study, carried out at Hospital Río Hortega (Valladolid, Spain), between June 2009 and May 2010. Data from 101 patients who presented to the emergency department experiencing abdominal pains were recovered. RESULTS: A total of 101 patients were included in the study: 55 were boys and 46 girls. The mean age was 9.51 (2.76) years. Diagnosis was acute appendicitis in 28 patients, adenitis in 8 patients, nonspecific abdominal pain in 51 patients, and other diagnoses in 14 patients. The mean (SD) PAS for children with and without appendicitis was 7.43 (1.79) and 4.97 (1.67), respectively (P < 0.001). CONCLUSIONS: With a cutoff PAS of 3 or lower, there were no patients diagnosed with acute appendicitis; hence, these patients could be discharged without any image studies. If all the patients with a PAS of 8 or higher undergo surgery, we would find in our sample a 4.95% rate of negative appendicectomy, less than other studies have shown. The application of this score in the emergency department could help in the decision making process, aiding in the identification of patients with a low risk of having appendicitis and enabling a better use of resources by avoiding unnecessary diagnostic tests.

Interleukin 10 decreases MICA expression on melanoma cell surface.

Natural-killer group 2, member D (NKG2D) binds to a variety of ligands, including the major histocompatibility complex (MHC) class I chain-related proteins (MIC) and UL16-binding proteins (ULBP). It is regarded as a co-activating receptor on NK cells, having an important role in the cell-mediated immune response to tumours. We studied the influence of interleukin (IL)-10 on the regulation of MIC and ULBP expression on melanoma cells, and its effect on the cytotoxic function of NK cells in vitro. Here, we show that, in the presence of IL-10, FMS mel and BL mel cell lines decreased MICA and ULBP2 surface expression, whereas MHC class I did not change substantially on the cell surface. MICA mRNA levels decreased in IL-10-treated FMS and IL-10-transduced BL cell lines. Interestingly, we observed that MICB surface expression and its mRNA levels increased upon IL-10 treatment in a melanoma cell line. These changes in NKG2D ligands surface expression patterns owing to IL-10 treatment resulted in an effect on lysis susceptibility mediated by lymphocyte-activated killer cells, as tumour cell lines that displayed a higher decrease of MICA on their surface had lower levels of lysis. In addition, expression of CD107a was downregulated on the surface of NK cells following stimulation with IL-10-treated FMS cells. Our results suggest a novel function for IL-10 in the modulation of NKG2D ligand expression and in the control of cytotoxicity mediated by NKG2D/NKG2D ligand axis.

Short-term lipopolysaccharide stimulation induces differentiation of murine bone marrow-derived dendritic cells into a tolerogenic phenotype.

Dendritic cells (DCs) are professional, antigen-presenting cells, which induce and regulate T cell reactivity. DCs are crucial in innate and adaptive immune responses, and are also involved in central and peripheral tolerance induction. Tolerance can be mediated by immature and semi-mature DCs expressing low levels of co-stimulator and major histocompatibility complex (MHC) molecules. The aim of this study was to investigate the ability of short-term lipopolysaccharide (LPS) stimulation to modulate the stage of differentiation of bone marrow-derived DCs. For this purpose, DCs obtained from DBA1/lacJ mice were stimulated for four (4hLPS/DCs) or 24 (24hLPS/DCs) hours with LPS, using DCs without stimulation (0hLPS/DCs) as a control. Flow cytometry analysis of 4hLPS/DCs showed intermediate CD40 and MHC class II expression, lower than that of 24hLPS/DCs (fully mature), and greater than that of 0hLPS/DCs (immature). A functional assay showed that 4hLPS/DCs displayed increased endocytotic ability compared to 24hLPS/DCs, indicating a semi-mature state. 4hLPS/DCs were greater producers of IL-10 protein and TGFbeta1 mRNA than 24hLPS/DCs and immature DCs, displaying a cytokine production pattern that is characteristic of tolerogenic DCs. An assay for antigen-presenting capacity demonstrated that 4hLPS/DCs induced secretion of IL-2 from an OTH4 T cell hybridoma, indicating a functional presenting activity. Finally, the tolerogenic phenotype of 4hLPS/DCs was demonstrated by their ability to interfere with the progression of bovine type II collagen (bII)-induced arthritis (CIA) when they were loaded with bCII antigen and injected into mice with established CIA. We conclude that the stimulation of murine bone marrow-derived DCs with LPS for four hours generates semi-mature DCs with tolerogenic capability.

Yeast system as a model to study Moloney murine leukemia virus integrase: expression, mutagenesis and search for eukaryotic partners.

Moloney murine leukemia virus (M-MuLV) integrase (IN) catalyses the insertion of the viral genome into the host chromosomal DNA. The limited solubility of the recombinant protein produced in Escherichia coli led the authors to explore the use of Saccharomyces cerevisiae for expression of M-MuLV IN. IN was expressed in yeast and purified by chromatography on nickel-NTA agarose. IN migrated as a single band in SDS-PAGE and did not contain IN degradation products. The enzyme was about twofold more active than the enzyme purified from E. coli and was free of nucleases. Using the yeast system, the substitution of the putative catalytic amino acid Asp184 by alanine was also analysed. The mutated enzyme was inactive in the in vitro assays. This is the first direct demonstration that mutation of Asp184 inactivates M-MuLV IN. Finally, S. cerevisiae was used as a model to assess the ability of M-MuLV IN to interact with eukaryotic protein partners. The expression of an active M-MuLV IN in yeast strains deficient in RAD52 induced a lethal effect. This phenotype could be attributed to cellular damage, as suggested by the viability of cells expressing inactive D184A IN. Furthermore, when active IN was expressed in a yeast strain lacking the ySNF5 transcription factor, the lethal effect was abolished, suggesting the involvement of ySNF5 in the cellular damage induced by IN. These results indicate that S. cerevisiae could be a useful model to study the interaction of IN with cellular components in order to identify potential counterparts of the natural host.