Estación de bomberos en la integración social de la ciudad de Casma, 2022

La presente investigación corresponde a la Estación de bomberos en la integración social de la ciudad de Casma, 2022. La problemática identificada corresponde a la falta de atención para las emergencias generadas por los incendios, tampoco existe una escuela de formación y capacitación que permita preparar al equipo del cuerpo general de bomberos voluntarios del Perú, para hacer frente a situaciones de crisis como parte de la gestión de riesgo de desastres. El objetivo es diseñar una estación de bomberos en Casma; para cubrir la demanda, debido al acelerado crecimiento poblacional y de su espacio geográfico. La metodología utilizada es de tipo básica, con diseño de estudio de casos: caso 1: Estación de Bomberos de Santo Tirso – Portugal y Caso 2: Estación de Bomberos de Yatsushiro – Japón. El escenario elegido es Casma y los participantes son los bomberos de la zona. Se han analizado artículos científicos y tesis. Como resultado se determina la importancia de la Estación de bomberos en la integración social de la ciudad de Casma, concluyendo que este proyecto arquitectónico brinda la posibilidad de atender las emergencias en el corto tiempo y, además, preparar a los aspirantes y convertirse en un espacio de interacción con la población

Rural and urban disparities in anemia among Peruvian children aged 6-59 months: a multivariate decomposition and spatial analysis

Introduction: Anemia is a global public health issue that affects mainly children aged less than 5 years. In Peru, despite the reduction in the prevalence of anemia between 2010 and 2018, anemia remains a major concern, especially in high-risk zones such as rural areas. Several sociodemographic factors have been associated with anemia in children; however, components contributing to the urban–rural gap have not been previously assessed. The purpose of this study was to evaluate the determinants of the difference in anemia prevalence between urban and rural areas, and its spatial distribution in Peruvian children aged 6–59 months. Methods: A secondary data analysis was conducted using the 2019 Peruvian Demographic Health Survey. The study population included 18 846 children aged 6–59 months. A multivariate decomposition analysis for non-linear response model was performed to identify the factors contributing to the gap in the prevalence of anemia across urban and rural areas. Global Moran's I autocorrelation, Ordinary Kriging interpolation and Bernoullibased purely spatial scan statistics were employed to assess the spatial pattern of anemia. Results: Nationwide, the prevalence of anemia in Peru was 29.47% (95%CI 28.63–30.33). In rural areas, it was 38.25%, and in urban areas 26.39%. The decomposition analysis revealed that 88.61% of the difference in the prevalence of anemia between urban and rural areas was attributed to the difference in the respondents’ characteristics. Wealth index, mother's education, mother's employment status, number of living children and mother's age were key determinants contributing to the rural–urban gap. Spatial heterogeneity of anemia prevalence in childhood was observed at both inter and intradepartmental level. The SaTScan spatial analysis identified six significant cluster areas with high prevalence of anemia in childhood. Conclusion: A considerable gap of anemia prevalence between urban and rural areas was found. Targeted interventions are necessary to reduce geographic disparities.Revisión por pare

Heme metabolism, oxidative and nitrosative markers in a mouse model of Hemochromatosis: Effect of Isoflurane, ethanol and 5-aminolevulinic acid

Hereditary hemochromatosis (HH) is characterized by iron homeostasis alterations. Association between HH and Porphyria Cutanea Tarda has been reported. The aim was to characterize oxidative and nitrosative stress status and its relationship with heme metabolism in a hemochromatosis mouse model (Hfe-/-), and to evaluate the effects of Isoflurane, ethanol and 5-aminolevulinic acid (ALA). Male and female Hfe−/− and wild-type C57BL/6J mice received Isoflurane (2 ml/kg); ethanol (30%) or ALA (40 mg/kg). In male Hfe-/-, reduced glutathione (GSH) was diminished respect to C57BL/6J mice. Female Hfe-/- showed higher levels of GSH and total antioxidant capacity than male Hfe-/-. Catalase activity was lower in male and female Hfe-/- than in controls. 5-Aminolevulinic acid synthetase activity was higher in male and female Hfe-/- than in controls. In male Hfe-/-, Porphobilinogen deaminase (PBG-D) activity was augmented and Heme oxygenase (HO) activity was diminished probably to avoid iron increase. Isoflurane and ethanol reduced PBG-D and increased HO activities. HO induction would indicate oxidative stress instauration being more striking due to ethanol that also induced Superoxide dismutase activity. Isoflurane reduced Nitric Oxide Synthase expression. ALA altered antioxidant system. In Hfe-/- mice different metabolisms were altered being more affected by the drugs studied. Findings here described would contribute to increase the knowledge about the association between HH and the Porphyrias and about the effects of volatile anaesthetics on different metabolisms in genetic models of Porphyrias and associated diseases.Fil: Buzaleh, Ana Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Centro de Invest. Sobre Porfirinas y Porfirias; Argentina. Hospital 12 de Octubre; España. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Moreno Carraledo, Maria. Hospital 12 de Octubre; EspañaFil: Mendez, Manuel. Hospital 12 de Octubre; EspañaFil: Batlle, Alcira Maria del C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Centro de Invest. Sobre Porfirinas y Porfirias; ArgentinaFil: Enriquez de Salamanca, Rafael. Hospital 12 de Octubre; EspañaFil: Moran Jimenez, Maria Jose. Hospital 12 de Octubre; Españ

Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity

Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTL) and natural killer cells (NK). Granzyme A is the most abundant of the different granzymes (gzms) expressed by these two cell types. Gzms A and K are found in all jawed vertebrates and are the most well conserved of all hematopoietic serine proteases. Their potential functions have been studied extensively for many years, however, without clear conclusions. Gzm A was for many years thought to serve as a key component in the defense against viral infection by the induction of apoptosis in virus-infected cells, similar to gzm B. However, later studies have questioned this role and instead indicated that gzm A may act as a potent inducer of inflammatory cytokines and chemokines. Gzms A and K form clearly separate branches in a phylogenetic tree indicating separate functions. Transcriptional analyses presented here demonstrate the presence of gzm A and K transcripts in both CD4+ and CD8+ T cells. To enable screening for their primary biological targets we have made a detailed analysis of their extended cleavage specificities. Phage display analysis of the cleavage specificity of the recombinant enzymes showed that both gzms A and K are strict tryptases with high selectivity for Arg over Lys in the P1 position. The major differences in the specificities of these two enzymes are located N-terminally of the cleavage site, where gzm A prefers small amino acids such as Gly in the P3 position and shows a relatively relaxed selectivity in the P2 position. In contrast, gzm K prefers large amino acids such as Phe, Tyr, and Trp in both the P2 and P3 positions and does not tolerate negatively charged residues in the P2 position. This major distinction in extended specificities is likely reflected also in preferred in vivo targets of these two enzymes. This information can now be utilized for high-precision screening of primary targets for gzms A and K in search of their highly conserved but still poorly defined functions in vertebrate immunity

Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy

mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-tooffspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission.Peer reviewe

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Use of spirometry-like measurements to monitor house dust mite-induced experimental asthma in mice

Weight and age correlated positively with FEV 0.1 and PEF among other lung function parameters in naïve mice. Lung function parameters decline in a model of experimental asthma induced by intranasal HDM administrations. Systemic injections of dexamethasone improved lung function, decreased mast cell populations and BAL levels of mast cell protease-1 in the HDM model