Progressive alterations in polysomal architecture and activation of ribosome stalling relief factors in a mouse model of Huntington's disease.

Given their highly polarized morphology and functional singularity, neurons require precise spatial and temporal control of protein synthesis. Alterations in protein translation have been implicated in the development and progression of a wide range of neurological and neurodegenerative disorders, including Huntington's disease (HD). In this study we examined the architecture of polysomes in their native brain context in striatal tissue from the zQ175 knock-in mouse model of HD. We performed 3D electron tomography of high-pressure frozen and freeze-substituted striatal tissue from HD models and corresponding controls at different ages. Electron tomography results revealed progressive remodelling towards a more compacted polysomal architecture in the mouse model, an effect that coincided with the emergence and progression of HD related symptoms. The aberrant polysomal architecture is compatible with ribosome stalling phenomena. In fact, we also detected in the zQ175 model an increase in the striatal expression of the stalling relief factor EIF5A2 and an increase in the accumulation of eIF5A1, eIF5A2 and hypusinated eIF5A1, the active form of eIF5A1. Polysomal sedimentation gradients showed differences in the relative accumulation of 40S ribosomal subunits and in polysomal distribution in striatal samples of the zQ175 model. These findings indicate that changes in the architecture of the protein synthesis machinery may underlie translational alterations associated with HD, opening new avenues for understanding the progression of the disease.

Comparative study of postpartum sexual function: Second-degree tears versus episiotomy outcomes.

PURPOSE: The effects of episiotomy and second-degree tears on postpartum sexual function are key areas of enquiry in women's health research. Episiotomy and second-degree tears are common procedures and injuries that occur during childbirth. Understanding their impact on post-childbirth sexuality is crucial to women's overall well-being. This study aimed to examine the relationship between episiotomy, second-degree tears, and post childbirth sexuality. METHODS: A cross-sectional design was employed, including 83 women who gave birth to Cáceres in 2017. Participants were evaluated based on sociodemographic and sexual health factors. RESULTS: No significant differences were found in dyspareunia or sexual function between women who underwent episiotomies and those with second-degree tears. However, women who underwent episiotomies waited longer before resuming sexual activity after childbirth. Factors such as age, number of previous births, employment status, educational level, and breastfeeding status affected the timing and frequency of postpartum sexual activity. CONCLUSION: Dyspareunia negatively affects various aspects of sexual function. When comparing episiotomy and second-degree tears, their impacts on postpartum sexual function were similar. However, episiotomy delays the resumption of sexual activity. Sociodemographic factors significantly influence postpartum sexual health. These findings highlight the importance of individualised interventions and support for new mothers during the postpartum period to address potential sexual health concerns.

The impact of teleworking technostress on satisfaction, anxiety and performance.

The aim of the research project is to find out how technostress influences the satisfaction, anxiety and performance of teleworkers and university students. The growth of technology and the use of digital platforms has given rise to a phenomenon called teleworking, a modality of work that involves remote work with the use of ICTs. However, the faster the use of ICTs in organisations grows, the more difficult it becomes for teleworkers, leading to anxiety and stress. This feeling is known as technostress, and knowing its impact on workers is of vital importance for organizational success. The study was conducted through a literature review and the dissemination of an online questionnaire using PLS software. The analysis validated the measurement scale and analysed the structural model at different stages, which confirmed its validity and reliability. The research concludes by affirming the high relationship between technostress, satisfaction, anxiety and performance. It is highlighted that the lower the technostress, the higher the satisfaction and performance, and the higher the technostress, the higher the anxiety and the lower the satisfaction. This research brings as an added value the validation of a scale of technostress together with the variables satisfaction, anxiety and performance not previously analysed by other researches. In addition, the research provides a series of measures to mitigate the effects of technostress and suggests future lines of research. Thus, it highlights the importance of understanding the impact of technostress on teleworkers, to provide effective measures to mitigate it and thus increase the satisfaction and performance of workers.

Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.

BACKGROUND & AIMS: Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response. METHODS: The intrahepatic localization of neutrophils was evaluated in patients with chronic liver disease. Neutrophil dynamics were analyzed by intravital microscopy and neutrophil-labeling assays in DDC-treated mice. Neutrophil depletion or inhibition of recruitment was achieved using a Ly6g antibody or a CXCR1/2 inhibitor, respectively. Mice deficient in PAD4 (peptidyl arginine deiminase 4) and ELANE/NE (neutrophil elastase) were used to investigate the mechanisms underlying ductular reaction expansion. RESULTS: In this study we describe a population of ductular reaction-associated neutrophils (DRANs), which are in direct contact with biliary epithelial cells in chronic liver diseases and whose numbers increased in parallel with disease progression. We show that DRANs are immobilized at the site of ductular reaction for a prolonged period of time. In addition, liver neutrophils display a unique phenotypic and transcriptomic profile, showing a decreased phagocytic capacity and increased oxidative burst. Depletion of neutrophils or inhibition of their recruitment reduces DRANs and the expansion of ductular reaction, while mitigating liver fibrosis and angiogenesis. Mechanistically, neutrophils deficient in PAD4 and ELANE abrogate neutrophil-induced biliary cell proliferation, thus indicating the role of neutrophil extracellular traps and elastase release in ductular reaction expansion. CONCLUSIONS: Overall, our study reveals the accumulation of DRANs as a hallmark of advanced liver disease and a potential therapeutic target to mitigate ductular reaction and the maladaptive wound-healing response. IMPACT AND IMPLICATIONS: Our results indicate that neutrophils are highly plastic and can have an extended lifespan. Moreover, we identify a new role of neutrophils as triggers of expansion of the biliary epithelium. Overall, the results of this study indicate that ductular reaction-associated neutrophils (or DRANs) are new players in the maladaptive tissue-healing response in chronic liver injury and may be a potential target for therapeutic interventions to reduce ductular reaction expansion and promote tissue repair in advanced liver disease.

Factors Associated with Quality of Life in Relatives of Adults with Serious Mental Illness: A Systematic Review.

Caring for a family member with a serious mental illness often has an impact on the quality of life (QoL) of caregivers. This could have negative repercussions on their caring skills and thus affect the care provided to that individual. The aim of this paper is to identify current evidence on QoL factors affecting relatives of individuals suffering from serious mental illness. A systematic review related to the research question was conducted in six databases by two independent reviewers. The QoL factors of relatives include sociodemographic, contextual, psychological, physical, and patient factors. The findings are consistent with the results of previous research. Mental health professionals may support a family with a member diagnosed with a serious mental illness by enhancing their education about QoL factors, which would trigger and promote protective factors so that family members could assess and act on them on an ongoing basis.

Embarazo en adolescentes. Análisis de natalidad en Perú y su relación con el Índice de Desarrollo Humano / Teenage pregnancy. Analysis of birth rate in Peru and its relationship with the Human Development Index

Resumen: OBJETIVO: Determinar la frecuencia de embarazos mediante la tasa de nacidos vivos en el grupo etario de 15 a 19 años y su asociación con el Índice de Desarrollo Humano (2016 a 2021). MATERIALES Y MÉTODOS: Estudio observacional, ecológico, exploratorio y correlacional efectuado con base en la información del Sistema de Registro del Certificado de Nacido Vivo en Línea y el Índice de Desarrollo Humano, que son datos por departamento, provincias y municipios. Se incluyeron todas las mujeres residentes en Perú con un recién nacido entre 2016 y 2021. Los datos registrados fueron: total de recién nacidos por departamento, región, provincia y distrito, divididos por grupos etarios de 15 a 19 años. Para el análisis de los datos se utilizaron regresión lineal y correlación de Pearson. RESULTADOS: En el periodo de estudio se registraron 2,843,903 nacimientos de los que 324,654 (11.41%) correspondieron a mujeres menores de 20 años. En el 2017 se registró la más alta cantidad de nacimientos en este grupo etario (n = 58,841). En 2016 el porcentaje más alto de nacimientos de hijos de adolescentes fue de 12.36% y el más bajo (10.51%) se registró en el 2020. CONCLUSIÓN: El porcentaje de adolescentes embarazadas disminuyó levemente en los últimos años, aunque hubo un ligero aumento en el 2021, sobre todo en la región de la selva, que es la de mayor proporción en comparación con las otras. El índice de desarrollo humano provincial y municipal está inversamente relacionado con la proporción de embarazos en adolescentes.

Abstract OBJECTIVE: To determine the frequency of pregnancies through the live birth rate in the 15-19 age group and its association with the Human Development Index (2016 to 2021). MATERIALS AND METHODS: Observational, ecological, exploratory, and correlational study carried out based on information from the Online Live Birth Certificate Registration System and the Human Development Index, which are data by department, provinces and municipalities. All women residing in Peru with a newborn between 2016 and 2021 were included. The data recorded were total newborns by department, region, province and district, divided by age groups from 15 to 19 years. Linear regression and Pearson correlation were used for data analysis. RESULTS: In the study period, 2,843,903 births were registered, of which 324,654 (11.41%) corresponded to women under 20 years of age. In 2017, the highest number of births was recorded in this age group (n = 58,841). In 2016, the highest percentage of births to teenagers was 12.36% and the lowest (10.51%) was recorded in 2020. CONCLUSION: The percentage of pregnant adolescents decreased slightly in recent years, although there was a slight increase in 2021, especially in the jungle region, which has the highest proportion compared to the others. The provincial and municipal human development index is inversely related to the proportion of teenage pregnancy.

Tendencia y distribución regional de la mortalidad materna en el Perú: 2015-2019 / Maternal mortality trend and regional distribution in Peru: 2015-2019

Resumen OBJETIVO: Describir la razón de mortalidad materna para 25 regiones peruanas entre 2015 y 2019, conocer su tendencia y algunos factores determinantes. MATERIALES Y MÉTODOS: Estudio retrospectivo y observacional efectuado con base en los casos de muerte materna registrados en el Repositorio Único Nacional de Información de Salud (REUNIS) del Perú de 2015 a 2019. Los datos se analizaron mediante la razón de mortalidad materna por 100,000 nacidos vivos. RESULTADOS: Se observó una tendencia de mortalidad materna descendente (415 casos en 2015 a 302, en 2019) y una razón de mortalidad materna de 76.34. La edad media fue 29.2 años (± 7.8). Las razones de mortalidad materna más altas se observaron en mujeres de la selva peruana (195.1), con parto domiciliario (1754.8) y atendidas en instituciones del primer nivel de atención (113.5). La región con más casos de muerte materna fue la Sierra peruana (37.61%). CONCLUSIÓN: En el periodo de estudio la razón de mortalidad materna en el Perú tuvo una ligera disminución, con una tendencia descendente. Solo 9 regiones lograron una razón de mortalidad materna menor de 70.

Abstract OBJECTIVE: Describe the trend and regional distribution of maternal mortality in Peru between 2015 and 2019. MATERIALS AND METHODS: A retrospective observational study was carried out based on the cases of maternal death (MM) registered in the National Repository of Health Information (REUNIS) of Peru between 2015 and 2019. The data were analyzed using the maternal mortality ratio (MMR) per 100,000 live births (NV). RESULTS: A descending maternal mortality trend was observed (415 cases in 2015 to 302 in 2019) and a MMR of 76.34. The mean age was 29.2 years (± 7.8). The highest MMRs were observed in women from the Peruvian jungle (195.1), with home birth (1754.8), and attended in institutions of the first level of care (113.5). The region with the most cases of MM was the Peruvian Sierra (37.61%). CONCLUSION: In the study period, the MMR in Peru had a slight decrease, with a downward trend. Only 9 regions achieved an MMR <70.

The Role of INAPERTURATE POLLEN1 as a Pollen Aperture Factor Is Conserved in the Basal Eudicot Eschscholzia californica (Papaveraceae).

Pollen grains show an enormous variety of aperture systems. What genes are involved in the aperture formation pathway and how conserved this pathway is in angiosperms remains largely unknown. INAPERTURATE POLLEN1 (INP1) encodes a protein of unknown function, essential for aperture formation in Arabidopsis, rice and maize. Yet, because INP1 sequences are quite divergent, it is unclear if their function is conserved across angiosperms. Here, we conducted a functional study of the INP1 ortholog from the basal eudicot Eschscholzia californica (EcINP1) using expression analyses, virus-induced gene silencing, pollen germination assay, and transcriptomics. We found that EcINP1 expression peaks at the tetrad stage of pollen development, consistent with its role in aperture formation, which occurs at that stage, and showed, via gene silencing, that the role of INP1 as an important aperture factor extends to basal eudicots. Using germination assays, we demonstrated that, in Eschscholzia, apertures are dispensable for pollen germination. Our comparative transcriptome analysis of wild-type and silenced plants identified over 900 differentially expressed genes, many of them potential candidates for the aperture pathway. Our study substantiates the importance of INP1 homologs for aperture formation across angiosperms and opens up new avenues for functional studies of other aperture candidate genes.

The multifaceted role of cathepsins in liver disease.

Proteases are the most abundant enzyme gene family in vertebrates and they execute essential functions in all living organisms. Their main role is to hydrolase the peptide bond within proteins, a process also called proteolysis. Contrary to the conventional paradigm, proteases are not only random catalytic devices, but can perform highly selective and targeted cleavage of specific substrates, finely modulating multiple essential cellular processes. Lysosomal protease cathepsins comprise 3 families of proteases that preferentially act within acidic cellular compartments, but they can also be found in other cellular locations. They can operate alone or as part of signalling cascades and regulatory circuits, playing important roles in apoptosis, extracellular matrix remodelling, hepatic stellate cell activation, autophagy and metastasis, contributing to the initiation, development and progression of liver disease. In this review, we comprehensively summarise current knowledge on the role of lysosomal cathepsins in liver disease, with a particular emphasis on liver fibrosis, non-alcoholic fatty liver disease and hepatocellular carcinoma.

Dating historical droughts from religious ceremonies, the international pro pluvia rogation database.

Climate proxy data are required for improved understanding of climate variability and change in the pre-instrumental period. We present the first international initiative to compile and share information on pro pluvia rogation ceremonies, which is a well-studied proxy of agricultural drought. Currently, the database has more than 3500 dates of celebration of rogation ceremonies, providing information for 153 locations across 11 countries spanning the period from 1333 to 1949. This product provides data for better understanding of the pre-instrumental drought variability, validating natural proxies and model simulations, and multi-proxy rainfall reconstructions, amongst other climatic exercises. The database is freely available and can be easily accessed and visualized via http://inpro.unizar.es/ .

Chaperonins: Nanocarriers with Biotechnological Applications.

Chaperonins are molecular chaperones found in all kingdoms of life, and as such they assist in the folding of other proteins. Structurally, chaperonins are cylinders composed of two back-to-back rings, each of which is an oligomer of ~60-kDa proteins. Chaperonins are found in two main conformations, one in which the cavity is open and ready to recognise and trap unfolded client proteins, and a "closed" form in which folding takes place. The conspicuous properties of this structure (a cylinder containing a cavity that allows confinement) and the potential to control its closure and aperture have inspired a number of nanotechnological applications that will be described in this review.

Caracterización clínico epidemiológica de la leishmaniosis visceral infantil / Clinical epidemiological characterization of children visceral leishmaniasis

Introducción: La leishmaniosis visceral es la más grave de las formas clínicas de la leishmaniosis, afecta principalmente a los niños y es potencialmente fatal. Objetivo: Exponer la caracterización clínico-epidemiológica de la leishmaniosis visceral en población pediátrica y su respuesta terapéutica. Métodos: Se realizó un estudio retrospectivo, longitudinal y descriptivo en el Hospital Italiano, Ciudad de Djibouti en el período septiembre 2016-agosto 2017. El universo lo conformaron 166 menores de 15 años que ingresaron con diagnóstico de fiebre prolongada sin foco de localización, la muestra fue de 22 niños con diagnóstico confirmado de leishmaniosis visceral. La información se obtuvo de las historias clínicas. Se operacionalizaron 20 variables: sociodemográficas, clínicas, analíticas, terapéuticas y evolutivas. Se utilizó el procesador Epidat 3.1. Los resultados se expresaron en valores absolutos y porcentajes. Resultados: Se diagnosticó leishmaniosis visceral en 13,2 por ciento de niños hospitalizados por fiebre prolongada, 90,9 por ciento de procedencia rural y 59,1 por ciento desnutridos. El 77,3 por ciento de los casos recibió antimoniales, 90,9 por ciento tuvo estadía hospitalaria mayor de 21 días y el 36,4 por ciento se complicó con neumonía. Conclusiones: La leishmaniosis visceral es una entidad relativamente frecuente en niños admitidos por fiebre prolongada en el Hospital Italiano, predominan los varones desnutridos, mayores de cinco años de edad, procedentes de zonas rurales. La fiebre y la esplenomegalia son manifestaciones clínicas constantes, la anemia y la leucopenia los principales hallazgos de laboratorio. La aplicación de antimoniales es el tratamiento electivo, con larga estadía hospitalaria y la neumonía es la complicación más frecuente(AU)

Introduction: Visceral leishmaniasis is the most severe clinical form of leishmaniasis that mainly affects children and is potentially fatal. Objective: To explain the clinical-epidemiological characterization of visceral leishmaniasis in the pediatric population and its therapeutic response. Methods: It was conducted a retrospective, longitudinal and descriptive study in the Italian Hospital, Djibouti City in the period from September 2016 to August 2017. The sample group was formed by 166 children under 15 years old that were admitted with a diagnosis of prolonged fever without localization focus and the sample was of 22 children with confirmed diagnosis of visceral leishmaniasis. The information was obtained from the clinical records. Twenty variables were operationalized: sociodemographic, clinical, analytical, therapeutic and evolutive ones. Epidat 3.1 proccessor was used. The results were expressed in absolute values and percentages. Results: Visceral leishmaniasis was diagnosed in 13.2 percent children that were admitted in hospital due to prolonged fever, 90.9 percent of them were from rural areas and 59.1 percent were undernourished. 77,3 percent of the cases had antimonial treatment, 90.9 percent had hospital stay for more than 21 days and the 36.4 percent had complications due to pneumonia. Conclusions: Visceral leishmaniasis is a relatively frequent entity in children admitted in the Italian Hospital due to prolonged fever with a predominance of undernourished males, older that five years and from rural areas. Fever and splenomegaly are constant clinical manifestations, and anemia and leucopenia are the main laboratory findings. The use of antimonials is the election treatment with long hospital stay, and pneumonia is the most frequent complication(AU)

PolishEM: image enhancement in FIB-SEM.

SUMMARY: We have developed a software tool to improve the image quality in focused ion beam-scanning electron microscopy (FIB-SEM) stacks: PolishEM. Based on a Gaussian blur model, it automatically estimates and compensates for the blur affecting each individual image. It also includes correction for artifacts commonly arising in FIB-SEM (e.g. curtaining). PolishEM has been optimized for an efficient processing of huge FIB-SEM stacks on standard computers. AVAILABILITY AND IMPLEMENTATION: PolishEM has been developed in C. GPL source code and binaries for Linux, OSX and Windows are available at http://www.cnb.csic.es/%7ejjfernandez/polishem. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effects of two emergency stabilization treatments on main soil properties four years after application in a severely burnt area.

In NW of the Iberian Peninsula, the incidence of anthropogenic fires is very high and, due to the climatologic and topographical conditions, burnt soils are prone to high erosion risks. In recent years several environmental management techniques (BAER: burnt area emergency response) have been applied after some wildfires, but there are still few field studies about their effects on soils (the foundations of terrestrial ecosystems) and most of them are short-term. Aiming to fill this gap of knowledge, sixteen properties useful as soil quality indices (pH, WHC, total N, δ15N, NH4+-N, NO3--N, and NH4Ac-DTPA extractable Na, K, Ca, Mg, P, Al, Fe, Mn, Cu and Zn) were studied four years after BAER application in a severely burnt area in the 0-2 and 2-5 cm depth layers of unburnt soil (US), burnt soil untreated (BS), and burnt soil treated with two BAERs techniques: rye seeding (BSS) and straw mulching (BSM). The effects of fire on soil WHC, total N, Mg, Na, P, Zn, NO3--N, Cu and K were mitigated in both BSS and BSM, but especially in the latter. The highest values for Ca and Mn were recorded in BSM. The BAER treatments affect NO3--N, Cu and K only in the top layer, but no clear effects were found for soil pH, δ15N, NH4+-N, Al and Fe. Soil samples were quite similarly grouped by the hierarchical cluster and the principal component analyses (PCA): a) 0-2 cm layers of US plots; b) 0-2 cm layers of BSM plots; c) 2-5 cm layers of US plots; d) most of top layers of BS and BSS plots; and e) most of the 2-5 cm layers of BS, BSM and BSS plots. The distribution of soil samples in the PCA showed that straw mulching and, to a lesser extent, rye seeding reduced the distance between burnt and unburnt topsoil along Factor 1, but not along Factor 2 (explaining 56% and 29% of the variance, respectively). Consequently, these BAER treatments mitigated, but not wiped out, the effects of fire on soil quality after four years.

Instrumento pronóstico de neumonía comunitaria complicada en niños / Prognostic instrument for complicated community pneumonia in children

Introducción: La neumonía comunitaria complicada es una entidad con gran impacto sobre la morbimortalidad pediátrica. Objetivo: Desarrollar un instrumento que permita pronosticar a los niños con alto riesgo de desarrollar neumonía comunitaria complicada. Métodos: Se realizó un estudio cuali-cuantitativo en el Hospital General Comandante Pinares de San Cristóbal, en el período 2013-2016 en dos etapas: una etapa diagnóstica inicial, en la que se efectuó un estudio de cohorte prospectivo observacional que permitió estimar la incidencia de neumonía complicada, describir sus características relevantes e identificar factores de riesgo. En una segunda etapa, se elaboró y validó un instrumento pronóstico de esta entidad. Resultados: La incidencia de neumonía complicada fue del 39,5 por ciento, identificándose seis factores de riesgo: hacinamiento [OR 1,9], fumador pasivo [OR 1,76], no lactancia materna exclusiva hasta el sexto mes [OR 1,85], anemia [OR 4,5], morbilidad infecciosa recurrente [OR 1,69] y uso reciente de antimicrobianos [OR 2,38]. Al aplicar el instrumento pronóstico se obtuvo una sensibilidad del 85,47 y una especificidad del 92,74. Conclusiones: La neumonía complicada es una entidad de presentación frecuente, identificándose seis factores de riesgo. El instrumento desarrollado pronostica la posibilidad de desarrollar neumonía complicada en niños con sensibilidad aceptable y alta especificidad(AU)

Introduction: Community complicated pneumonia is an entity with great impact on morbidity and mortality in children. Objective: To develop an instrument that allows prognosticating children at high risk of developing community complicated pneumonia. Methods: A qualitative-quantitative study was carried out at Comandante Pinares General Hospital, San Cristobal municipality, in the period from 2013 to 2016 in two stages: an initial diagnostic stage, in which it was performed a prospective observational cohort study that allowed to estimate the incidence of complicated pneumonia, to describe its relevant characteristics and identify risk factors. In a second stage, it was developed and validated a prognosis instrument for this entity. Results: The incidence of complicated pneumonia was 39.5 por ciento identifying six risk factors: overcrowding (OR 1.9), passive smoking (OR 1.76), not exclusive breastfeeding until the sixth month (OR 1.85), anemia (OR 4.5), recurrent infectious morbidity (OR 1.69), and recent use of antimicrobials (OR 2.38). When the prognosis instrument was applied, it was obtained a sensitivity of 85.47 and a specificity of 92.74. Conclusions: Complicated pneumonia is an entity of frequent presentation. Six risk factors were identified. The instrument predicts the possibility of developing complicated pneumonia in children with acceptable sensitivity and high specificity(AU)

Perfil microbiológico en servicio de Neonatología / Microbiological profile in the Neonatology service

RESUMEN Se realizó este estudio en el servicio de Neonatología del Hospital Universitario Pediátrico José Luis Miranda, de Santa Clara, en el período de junio 2015 - mayo 2016. Se analizaron los aislamientos de microorganismos en los cultivos realizados a los neonatos hospitalizados, con el objetivo de investigar la prevalencia y sensibilidad de estos gérmenes. Se confirmaron 69 aislamientos, en los cuales predominaron los gérmenes grampositivos; el estafilococo prevaleció de forma significativa y ofreció resistencia creciente a cefazolina. Dentro de los gramnegativos, la escherichia coli resultó el microorganismo con mayor aislamiento, mientras que el acinetobacter se comportó resistente a las cefalosporinas.

ABSTRACT A study was carried out in the Neonatology service at "José Luis Miranda" Pediatric University Hospital, in Santa Clara, from June, 2015 to May, 2016. The isolations of microorganisms in the cultures performed on hospitalized neonates were analyzed with the aim of investigating the prevalence and sensitivity of these germs. Sixty-nine isolates were confirmed, in which the gram-positive ones predominated; staphylococcus prevailed significantly and offered a high resistance to cefazolin. Escherichia coli was the microorganism with the highest isolation among the gram-negative bacteria, while acinetobacter exhibited resistant to cephalosporins.

Overweight in the Elderly Induces a Switch in Energy Metabolism that Undermines Muscle Integrity.

Aging is characterized by a progressive loss of skeletal muscle mass and function (sarcopenia). Obesity exacerbates age-related decline and lead to frailty. Skeletal muscle fat infiltration increases with aging and seems to be crucial for the progression of sarcopenia. Additionally, skeletal muscle plasticity modulates metabolic adaptation to different pathophysiological situations. Thus, cellular bioenergetics and mitochondrial profile were studied in the skeletal muscle of overweight aged people without reaching obesity to prevent this extreme situation. Overweight aged muscle lacked ATP production, as indicated by defects in the phosphagen system, glycolysis and especially mostly by oxidative phosphorylation metabolic pathway. Overweight subjects exhibited an inhibition of mitophagy that was linked to an increase in mitochondrial biogenesis that underlies the accumulation of dysfunctional mitochondria and encourages the onset of sarcopenia. As a strategy to maintain cellular homeostasis, overweight subjects experienced a metabolic switch from oxidative to lactic acid fermentation metabolism, which allows continued ATP production under mitochondrial dysfunction, but without reaching physiological aged basal levels. This ATP depletion induced early signs of impaired contractile function and a decline in skeletal muscle structural integrity, evidenced by lower levels of filamin C. Our findings reveal the main effector pathways at an early stage of obesity and highlight the importance of mitochondrial metabolism in overweight and obese individuals. Exploiting mitochondrial profiles for therapeutic purposes in humans is an ambitious strategy for treating muscle impairment diseases.

Expression of LAIR-1 (CD305) on Human Blood Monocytes as a Marker of Hepatic Cirrhosis Progression.

BACKGROUND AND AIM: The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis. METHODS: The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot. RESULTS: We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls. CONCLUSIONS: These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.

Association of single nucleotide polymorphisms at HSPB1 rs7459185 and TGFB1 rs11466353 with radiation esophagitis in lung cancer.

BACKGROUND AND PURPOSE: Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness. MATERIALS AND METHODS: 247 LC patients prospectively recruited between 2012 and 2016 from 3 institutions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan-Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk. RESULTS: Multivariate analyses showed that patients carrying the HSPB1 rs7459185 CC genotype were associated with a significantly higher risk of acute grade 3 RIET than those carrying the GG/GC genotypes (HR = 17.73; 95% CI = 2.896-108.49; p = 0.002). LC patients who received higher (>median) volume of esophagus exposed to 30 Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (p < 0.001). Additionally, LC patients carrying the TGFB1 rs11466353 GG genotype were found to be associated with a lower risk of late grade 2 RIET compared with those with the TT/TG genotypes (HR = 0.29; 95% CI = 0.103-0.830; p = 0.021). Patients receiving a high (>60 Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (p = 0.025). CONCLUSION: The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.

Hsp70 chaperone: a master player in protein homeostasis.

Protein homeostasis (proteostasis) is an essential pillar for correct cellular function. Impairments in proteostasis are encountered both in aging and in several human disease conditions. Molecular chaperones are important players for proteostasis; in particular, heat shock protein 70 (Hsp70) has an essential role in protein folding, disaggregation, and degradation. We have recently proposed a model for Hsp70 functioning as a "multiple socket". In the model, Hsp70 provides a physical platform for the binding of client proteins, other chaperones, and cochaperones. The final fate of the client protein is dictated by the set of Hsp70 interactions that occur in a given cellular context. Obtaining structural information of the different Hsp70-based protein complexes will provide valuable knowledge to understand the functional mechanisms behind the master role of Hsp70 in proteostasis. We additionally evaluate some of the challenges for attaining high-resolution structures of such complexes.