Zonal expression of StARD1 and oxidative stress in alcoholic-related liver disease.

Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely understood. StARD1 has emerged as a key player in other etiologies of chronic liver disease, and alcohol-induced liver injury exhibits zonal distribution. Here, we report that StARD1 is predominantly expressed in perivenous (PV) zone of liver sections from mice-fed chronic and acute-on-chronic ALD models compared to periportal (PP) area and is observed as early as 10 days of alcohol feeding. Ethanol and chemical hypoxia induced the expression of StARD1 in isolated primary mouse hepatocytes. The zonal-dependent expression of StARD1 resulted in the accumulation of cholesterol in mitochondria and increased lipid peroxidation in PV hepatocytes compared to PP hepatocytes, effects that were abrogated in PV hepatocytes upon hepatocyte-specific Stard1 KO mice. Transmission electron microscopy indicated differential glycogen and lipid droplets content between PP and PV areas, and alcohol feeding decreased glycogen content in both areas while increased lipid droplets content preferentially in PV zone. Moreover, transmission electron microscopy revealed that mitochondria from PV zone exhibited reduced length with respect to PP area, and alcohol feeding increased mitochondrial number, particularly, in PV zone. Extracellular flux analysis indicated lower maximal respiration and spared respiratory capacity in control PV hepatocytes that were reversed upon alcohol feeding. These findings reveal a differential morphology and functional activity of mitochondria between PP and PV hepatocytes following alcohol feeding and that StARD1 may play a key role in the zonal-dependent liver injury characteristic of ALD.

Characterization of microglia behaviour in healthy and pathological conditions with image analysis tools.

Microglia are very sensitive to changes in the environment and respond through morphological, functional and metabolic adaptations. To depict the modifications microglia undergo under healthy and pathological conditions, we developed free access image analysis scripts to quantify microglia morphologies and phagocytosis. Neuron-glia cultures, in which microglia express the reporter tdTomato, were exposed to excitotoxicity or excitotoxicity + inflammation and analysed 8 h later. Neuronal death was assessed by SYTOX staining of nucleus debris and phagocytosis was measured through the engulfment of SYTOX+ particles in microglia. We identified seven morphologies: round, hypertrophic, fried egg, bipolar and three 'inflamed' morphologies. We generated a classifier able to separate them and assign one of the seven classes to each microglia in sample images. In control cultures, round and hypertrophic morphologies were predominant. Excitotoxicity had a limited effect on the composition of the populations. By contrast, excitotoxicity + inflammation promoted an enrichment in inflamed morphologies and increased the percentage of phagocytosing microglia. Our data suggest that inflammation is critical to promote phenotypical changes in microglia. We also validated our tools for the segmentation of microglia in brain slices and performed morphometry with the obtained mask. Our method is versatile and useful to correlate microglia sub-populations and behaviour with environmental changes.

Aberrant TIMP-1 overexpression in tumor-associated fibroblasts drives tumor progression through CD63 in lung adenocarcinoma.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important regulator of extracellular matrix turnover that has been traditionally regarded as a potential tumor suppressor owing to its inhibitory effects of matrix metalloproteinases. Intriguingly, this interpretation has been challenged by the consistent observation that increased expression of TIMP-1 is associated with poor prognosis in virtually all cancer types including lung cancer, supporting a tumor-promoting function. However, how TIMP-1 is dysregulated within the tumor microenvironment and how it drives tumor progression in lung cancer is poorly understood. We analyzed the expression of TIMP-1 and its cell surface receptor CD63 in two major lung cancer subtypes: lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), and defined the tumor-promoting effects of their interaction. We found that TIMP-1 is aberrantly overexpressed in tumor-associated fibroblasts (TAFs) in ADC compared to SCC. Mechanistically, TIMP-1 overexpression was mediated by the selective hyperactivity of the pro-fibrotic TGF-ß1/SMAD3 pathway in ADC-TAFs. Likewise, CD63 was upregulated in ADC compared to SCC cells. Genetic analyses revealed that TIMP-1 secreted by TGF-ß1-activated ADC-TAFs is both necessary and sufficient to enhance growth and invasion of ADC cancer cells in culture, and that tumor cell expression of CD63 was required for these effects. Consistently, in vivo analyses revealed that ADC cells co-injected with fibroblasts with reduced SMAD3 or TIMP-1 expression into immunocompromised mice attenuated tumor aggressiveness compared to tumors bearing parental fibroblasts. We also found that high TIMP1 and CD63 mRNA levels combined define a stronger prognostic biomarker than TIMP1 alone. Our results identify an excessive stromal TIMP-1 within the tumor microenvironment selectively in lung ADC, and implicate it in a novel tumor-promoting TAF-carcinoma crosstalk, thereby pointing to TIMP-1/CD63 interaction as a novel therapeutic target in lung cancer.

Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation.

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

Swept-source optical coherence tomography objective composite activity score for uveitis.

PURPOSE: To develop an objective intraocular inflammation composite score. METHODS: Cross-sectional study. Non-invasive image acquisition and processing were conducted from April 2017 to April 2019. Inflammation-grade stratified eyes from patients with active, inactive uveitis and healthy controls were recruited. After clinical assessment, four anterior and posterior segment image acquisition protocols per eye, using swept-source optical coherence tomography (SS-OCT), were performed at inclusion. Eight imaging biomarkers in three domains: anterior, intermediate and posterior were studied. They were ranked and selected by discriminatory power and correlation with clinical scores. A final SS-OCT-derived composite uveitis activity score (SS-UAS) was developed through multiple linear regression. RESULTS: We studied 224 eyes with uveitis (165 active and 59 inactive) from 165 patients (mean age 46.6 SD 15.5 years; 55.3% women) and 38 eyes from 19 healthy controls (mean age 43.6 SD 17.1; 47% women). The selected SS-OCT-derived biomarkers to build the final score were anterior chamber hyper-reflective dots (anterior), high-definition relative vitreous intensity (intermediate) and the averaged thickened retinal index (posterior). Swept-source (SS)-UAS was highly discriminant between active and inactive, and between active and healthy eyes (means 2.06 SD 1.86, 0.93 SD 0.44, and 0.96 SD 0.38, respectively, both p -, Mann-Whitney U). Construct validity (Cronbach's alpha = 0.7), internal consistency, criterion validity and reliability (concordance correlation coefficient intra-rater = 0.99, 95% CI: 0.98-0.99; inter-rater = 0.98, 95% CI: 0.96-0.99) were favourable. CONCLUSIONS: Global intraocular inflammation can potentially be staged and scored objectively, continuously, consistently and in a valid manner through the combined processing of SS-OCT scans.

Palliative Care Physicians and Palliative Radiotherapy, Knowledge and Barriers for Referring: A Cross-sectional Study.

CONTEXT: Palliative radiotherapy is effective in the management of symptoms resulting from advanced cancer. However, it remains underutilized. In developed countries, many factors have been linked to this phenomenon but data in developing and low-income countries, particularly in Latin America, are lacking. OBJECTIVES: To conduct a cross-sectional survey to explore palliative care physicians' knowledge of palliative radiotherapy and to investigate possible factors that limit patient referral. METHODS: This is a cross-sectional survey. An online questionnaire was sent to palliative care physicians (n = 170) registered in the Chilean Medical Society of Palliative Care directory. RESULTS: The overall response rate was 58.8%. Nearly all respondents (98%) considered radiotherapy to be a useful treatment. Less than half the respondents (43%) had good knowledge of palliative radiotherapy. Knowledge was correlated with self-reported knowledge (P = 0.015), discussing cases with radiation oncologist (P = 0.001), and having attended educational events on palliative radiotherapy (P = 0.001). Patient reluctance, poor performance status, and family reluctance were identified as major barriers to the use of palliative radiotherapy. Physicians from cities other than the capital were more likely to be concerned about barriers such as distance to radiotherapy facilities (P = 0.01), the duration of the referral process (P = 0.01), and the lack of a radiation oncologist available for discussing cases (P = 0.01). CONCLUSIONS: Several barriers affect referral to palliative radiotherapy. Some barriers seem to be more significant for physicians practicing in cities far from cancer centers. Physicians' knowledge is less than optimal and has been identified as a barrier to referral. Educational interventions and broadening the availability of cancer treatment resources are needed to improve the referral process.

Automated Quantitative Analysis of Mitochondrial Morphology.

Mitochondria are dynamic organelles that in most cells behave as a dynamic network and can change their biogenesis and structure depending on the cell needs or as a response to different conditions. Analyzing the architecture of mitochondria is determinant to describe their state and function. In this chapter, image processing techniques are applied in a workflow manner to segment the mitochondrial network and extract the most relevant parameters that enable an accurate morphology analysis. This workflow is programmed with ImageJ macro language and can be applied to automatically analyze multiple cells from multiple images or tiles. When combined with multiwell plates and automated microscopy, this method may allow to perform high content image analysis of hundreds of cells under different conditions.

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation.

Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood-brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow. Based on previous observations of microglia phagocytosing neutrophils recruited to the ischemic brain lesion, we hypothesized that microglial cells might control neutrophil accumulation in the injured brain. We studied a model of permanent occlusion of the middle cerebral artery in mice, including microglia- and neutrophil-reporter mice. Using various in vitro and in vivo strategies to impair microglial function or to eliminate microglia by targeting colony stimulating factor 1 receptor (CSF1R), this study demonstrates that microglial phagocytosis of neutrophils has fundamental consequences for the ischemic tissue. We found that reactive microglia engulf neutrophils at the periphery of the ischemic lesion, whereas local microglial cell loss and dystrophy occurring in the ischemic core are associated with the accumulation of neutrophils first in perivascular spaces and later in the parenchyma. Accordingly, microglia depletion by long-term treatment with a CSF1R inhibitor increased the numbers of neutrophils and enlarged the ischemic lesion. Hence, microglial phagocytic function sets a critical line of defense against the vascular and tissue damaging capacity of neutrophils in brain ischemia.

Reference interval for immature platelet fraction on Sysmex XN haematology analyser in adult population.

INTRODUCTION: The Sysmex XN-series haematology analyser has newly adopted a fluorescent channel to measure immature platelet fraction (IPF). To promote the clinical utility of this promising parameter, establishing a reliable reference interval is mandatory. According to previous studies, IPF values may be affected by the employed analyser and the ethnic background of the individual, but no differences seem to be found between individuals' genders. Therefore, this study aimed to define the reference interval for IPF in a Spanish population following Clinical and Laboratory Standard Institute (CLSI) guidelines. MATERIALS AND METHODS: A total of 153 healthy Caucasian adults from Spain met the inclusion criteria. IPF measurement was performed by means of a Sysmex XN-2000 haematology analyser. A non-parametric percentile method was used to calculate the reference intervals in accordance with CLSI guidelines. RESULTS: The obtained reference interval for IPF on the Sysmex XN-2000 was 1.6-9.6% (90% confidence intervals (CIs) were 1.5-1.8 and 9.3-11.5, respectively). No significant gender difference in IPF reference intervals was observed (P = 0.101). CONCLUSIONS: This study provides, for the first time, a reference interval for IPF using a Sysmex XN-2000 in a Spanish population, ranging from 1.6 to 9.6%. These data are needed to evaluate platelet production in several conditions such as thrombocytopenia, inflammatory states and cardiovascular diseases, as well as for future research.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl4-treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-ß1 (TGF-ß1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis (P < 0.05) and an improvement in the vascular disorganization rate (P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization.NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-ß1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization.

Isolation Methods of Peripheral Blood Mononuclear Cells in Spanish Biobanks: An Overview.

The Spanish Hematic Derivatives Group, consisting of 26 biobanks, was established in 2011. We describe here the viability results of our publically available standard operating procedure to freeze and thaw peripheral blood mononuclear cells (PBMCs). Our protocol maximizes PBMC viability while avoiding where possible interbiobank and intrabiobank assay variability.

Transcription-dependent radial distribution of TCF7L2 regulated genes in chromosome territories.

Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR. Our results confirmed that the two over-expressed genes, MYC on chromosome 8 and CCND1 on chromosome 11, are located significantly further away from the center of the CT compared to under-expressed genes on the same chromosomes, i.e., DLC1 and SCN3B. When CCND1 expression was reduced after silencing the major transcription factor of the WNT/ß-catenin signaling pathway, TCF7L2, the gene was repositioned and mostly detected in the interior of the CT. Thus, we suggest a non-random distribution in which over-expressed genes are located more towards the periphery of the respective CTs.

Epidemiology of sepsis in Catalonia: analysis of incidence and outcomes in a European setting.

BACKGROUND: Up-to-date identification of local trends in sepsis incidence and outcomes is of considerable public health importance. The aim of our study was to estimate annual incidence rates and in-hospital mortality trends for hospitalized patients with sepsis in a European setting, while avoiding selection bias in relation to different complexity hospitals. METHODS: A large retrospective analysis of a 5-year period (2008-2012) was conducted of hospital discharge records obtained from the Catalan Health System (CatSalut) Minimum Basic Data Set for Acute-Care Hospitals (a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia). Patients hospitalized with sepsis were detected on the basis of ICD-9-CM codes used to identify acute organ dysfunction and infectious processes. RESULTS: Of 4,761,726 discharges from all acute-care hospitals in Catalonia, 82,300 cases (1.72%) had sepsis diagnoses. Annual incidence was 212.7 per 100,000 inhabitants/year, rising from 167.2 in 2008 to 261.8 in 2012. Length of hospital stay fell from 18.4 to 15.3 days (p < .00001), representing a relative reduction of 17%. Hospital mortality fell from 23.7 to 19.7% (p < .0001), representing a relative reduction of 16.9%. These differences were confirmed in the multivariate analysis (adjusted for age group, sex, comorbidities, ICU admission, emergency admission, organ dysfunction, number of organ failures, sepsis source and bacteraemia). CONCLUSIONS: Sepsis incidence has risen in recent years, whereas mortality has fallen. Our findings confirm reports for other parts of the world, in the context of scarce administrative data on sepsis in Europe.

[Road traffic injuries in Catalonia (Spain): an approach using the minimum data set for acute-care hospitals and emergency resources]. / Lesiones por accidente de tráfico: aproximación desde el conjunto mínimo básico de datos de urgencias y hospitalización de agudos de Cataluña.

OBJECTIVE: To verify the usefulness of the minimum data set (MDS) for acute-care hospitals and emergency resources for the study of road traffic injuries and to describe the use of health resources in Catalonia (Spain). METHODS: The study population consisted of patients treated in any kind of emergency service and patients admitted for acute hospitalization in Catalonia in 2013. A descriptive analysis was performed by age, gender, time and clinical variables. RESULTS: A total of 48,150 patients were treated in hospital emergency departments, 6,210 were attended in primary care, and 4,912 were admitted to hospital. There was a higher proportion of men (56.2%), mainly aged between 20 and 40 years. Men accounted for 54.9% of patients with minor injuries and 75.1% of those with severe injuries. Contusions are the most common injury (30.2%), followed by sprains (28.7%). Fractures mostly affected persons older than 64 years, internal injuries particularly affected men older than 64 years, and wounds mainly affected persons younger than 18 years and older than 64 years. In the adult population, the severity of the injuries increased with age, leading to longer length of stay and greater complexity. Hospital mortality was 0.2%. Fractures, internal injuries and wounds were more frequent in the group of very serious injuries, and sprains and contusions in the group of minor injuries. CONCLUSIONS: MDS records (acute hospitals and emergency resources) provide information that is complementary to other sources of information on traffic accidents, increasing the completeness of the data.

Lesiones por accidente de tráfico: aproximación desde el conjunto mínimo básico de datos de urgencias y hospitalización de agudos de Cataluña / Road traffic injuries in Catalonia (Spain): an approach using the minimum data set for acute-care hospitals and emergency resources

Objetivo: Verificar la utilidad del conjunto mínimo básico de datos (CMBD) para el estudio de las lesiones por accidente de tráfico y describir la utilización de recursos sanitarios en Cataluña. Métodos: Análisis descriptivo por edad, sexo, variables de tiempo y morbilidad de los pacientes lesionados por colisión de tráfico, atendidos en recursos de urgencias durante el año 2013 (CMBD de urgencias y de hospitalización). Resultados: Se analizan 48.150 pacientes atendidos en urgencias hospitalarias, 6210 en dispositivos urgentes de atención primaria y 4912 ingresados. Se observa una mayor proporción de hombres (56,2%), sobre todo entre 20 y 40 años de edad. Los hombres representan el 54,9% de los casos con lesiones leves y el 75,1% de los que presentan lesiones muy graves. Las contusiones son la lesión más frecuente (30,2%), seguidas de los esguinces (28,7%). Las fracturas afectan sobre todo a las personas mayores de 64 años, las lesiones internas principalmente a los hombres mayores de 64 años y las heridas a las personas menores de 18 años y mayores de 64 años. En la población adulta, la gravedad de las lesiones aumenta con la edad y comporta un aumento en la estancia y la complejidad. La mortalidad hospitalaria es del 0,2%. Las fracturas, las lesiones internas y las heridas son más frecuentes en el grupo de personas lesionadas muy graves, y los esguinces y las contusiones en el de las personas lesionadas leves. Conclusiones: Los registros del CMBD (hospitales de agudos y recursos de urgencias) proporcionan información complementaria a otras fuentes sobre las colisiones de tráfico y aumentan la exhaustividad de los datos (AU)

Objective: To verify the usefulness of the minimum data set (MDS) for acute-care hospitals and emergency resources for the study of road traffic injuries and to describe the use of health resources in Catalonia (Spain). Methods: The study population consisted of patients treated in any kind of emergency service and patients admitted for acute hospitalization in Catalonia in 2013. A descriptive analysis was performed by age, gender, time and clinical variables. Results: A total of 48,150 patients were treated in hospital emergency departments, 6,210 were attended in primary care, and 4,912 were admitted to hospital. There was a higher proportion of men (56.2%), mainly aged between 20 and 40 years. Men accounted for 54.9% of patients with minor injuries and 75.1% of those with severe injuries. Contusions are the most common injury (30.2%), followed by sprains (28.7%). Fractures mostly affected persons older than 64 years, internal injuries particularly affected men older than 64 years, and wounds mainly affected persons younger than 18 years and older than 64 years. In the adult population, the severity of the injuries increased with age, leading to longer length of stay and greater complexity. Hospital mortality was 0.2%. Fractures, internal injuries and wounds were more frequent in the group of very serious injuries, and sprains and contusions in the group of minor injuries. Conclusions: MDS records (acute hospitals and emergency resources) provide information that is complementary to other sources of information on traffic accidents, increasing the completeness of the data (AU)

[Can psychopathy be detected psychophysiologically?]. / Ist Psychopathie psychophysiologisch fassbar?

The aim of the present study was to determine whether pupillometry was able to identify and differentiate psychopathic personality traits in criminally responsible mentally disordered offenders (§ 21/2 StGB). Psychopathic disorder has not only behavioral, but also psychophysiological correlates, which may be evaluated by pupillometry. This might make it possible to diagnose psychopathy by means of a non-invasive method and in a further step to adapt therapeutic measures accordingly. Psychopathic behavior and personality traits were identified by means of the Hare Psychopathy Checklist-Revised (PCL-R) and offenders were divided into 4 groups with PCL-R scores of 0-10, 11-20, 21-30 and 31-40, respectively. Pupillometry makes it possible to objectively measure amplitudes of pupillary oscillations, which may serve as an indicator of central nervous activation/deactivation. The study at hand showed that the higher the PCL-R values, the smaller the amplitudes. Thus, it can be concluded that central nervous activation decreases with higher PCL-R values and psychopathy is associated with central nervous deactivation.

A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation.

Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT.

Análisis comparativo de las serologías realizadas a los inmigrantes en la región sanitaria de Lleida / Comparative analysis of serological tests performed in immigrants in the lleida health area

Objetivo: Evaluar el proceso de cribado y detección de virus de la inmunodeficiencia humana (VIH), virus de la hepatitis B (VHB) y de la hepatitis C (VHC) y sífilis en los inmigrantes de nuestra región sanitaria, determinando las proporciones de resultados positivos entre colectivos durante un año. Diseño: Estudio descriptivo multicéntrico donde se analizaron todas las serologías realizadas a inmigrantes y autóctonos atendidos durante todo el año 2007. Emplazamiento: Provincia de Lleida (España). Participantes: Se incluyeron 255.410 usuarios. Mediciones principales: Edad, sexo, país de origen y tiempo de permanencia en nuestro país y los resultados para VIH, hepatitis B, hepatitis C y sífilis. Se evaluó si había asociación entre las tasas de marcadores positivos y la zona geográfica de procedencia. Se calcularon las tasas ajustadas por grupos de edad estandarizadas según el método directo. Resultados: El colectivo de origen inmigrante presenta 4,6 veces más probabilidades de tener VHB que el colectivo autóctono (razón de porcentajes [RP]=4,6), siendo el colectivo sudafricano y de Europa del Este el que presenta una mayor probabilidad de VHB (RP=11,7 y 4,5). En la sífilis el porcentaje de positivos es 3 veces mayor en el colectivo inmigrante con las diferencias mayores detectadas en el colectivo latinoamericano (RP=5,5). En el VIH la RP en inmigrantes fue de 2,3 (específicamente en subsaharianos una RP=7,4). En la hepatitis C los inmigrantes obtienen un menor riesgo de ser positivos que los autóctonos (RP=0,4). Conclusiones: Se constatan diferencias importantes en la probabilidad de detectar un resultado positivo de hepatitis B, sífilis o VIH en el cribado cuando el usuario es de origen inmigrante(AU)

Objective: Evaluate the process of screening and detection of HIV, HBV, HCV and syphilis in the province of Lleida by determining the proportions of positive results in the different groups during one year. Design: Descriptive, multicentre study of all the serological tests performed in immigrants and natives attended in 2007.SettingProvince of Lleida (Spain). Participants: 255,410 users. Main measurements: Age, sex, country of origin and period of residence in Spain, and the results for HIV, hepatitis B, hepatitis C and syphilis. We calculated the proportions in which a serological test had been requested, and examined the association between the rates of positive tests and the geographical area of origin, and calculated age-adjusted rates taking the age distribution of the native population as the reference. Results: Risk of HBV was 4.6 times higher in immigrants than in natives (11.7 times in sub-Saharan Africans). The rate of positive syphilis tests was three times higher in the immigrant group. For HIV the PR was 2.3 (sub-Saharan Africans 7.4). For hepatitis C the risk was lower in immigrants than in natives (PR=0.4). Conclusions: Immigrants have a higher probability of testing positive in screening in hepatitis B, syphilis and HIV. The rates differ significantly according to the origin of the immigrant(AU)

Approximation and spatial regionalization of rainfall erosivity based on sparse data in a mountainous catchment of the Yangtze River in Central China.

In densely populated countries like China, clean water is one of the most challenging issues of prospective politics and environmental planning. Water pollution and eutrophication by excessive input of nitrogen and phosphorous from nonpoint sources is mostly linked to soil erosion from agricultural land. In order to prevent such water pollution by diffuse matter fluxes, knowledge about the extent of soil loss and the spatial distribution of hot spots of soil erosion is essential. In remote areas such as the mountainous regions of the upper and middle reaches of the Yangtze River, rainfall data are scarce. Since rainfall erosivity is one of the key factors in soil erosion modeling, e.g., expressed as R factor in the Revised Universal Soil Loss Equation model, a methodology is needed to spatially determine rainfall erosivity. Our study aims at the approximation and spatial regionalization of rainfall erosivity from sparse data in the large (3,200 km(2)) and strongly mountainous catchment of the Xiangxi River, a first order tributary to the Yangtze River close to the Three Gorges Dam. As data on rainfall were only obtainable in daily records for one climate station in the central part of the catchment and five stations in its surrounding area, we approximated rainfall erosivity as R factors using regression analysis combined with elevation bands derived from a digital elevation model. The mean annual R factor (R a) amounts for approximately 5,222 MJ mm ha(-1) h(-1) a(-1). With increasing altitudes, R a rises up to maximum 7,547 MJ mm ha(-1) h(-1) a(-1) at an altitude of 3,078 m a.s.l. At the outlet of the Xiangxi catchment erosivity is at minimum with approximate R a=1,986 MJ mm ha(-1) h(-1) a(-1). The comparison of our results with R factors from high-resolution measurements at comparable study sites close to the Xiangxi catchment shows good consistance and allows us to calculate grid-based R a as input for a spatially high-resolution and area-specific assessment of soil erosion risk.

[Comparative analysis of serological tests performed in immigrants in the Lleida health area]. / Análisis comparativo de las serologías realizadas a los inmigrantes en la región sanitaria de Lleida.

OBJECTIVE: Evaluate the process of screening and detection of HIV, HBV, HCV and syphilis in the province of Lleida by determining the proportions of positive results in the different groups during one year. DESIGN: Descriptive, multicentre study of all the serological tests performed in immigrants and natives attended in 2007. SETTING: Province of Lleida (Spain). PARTICIPANTS: 255,410 users. MAIN MEASUREMENTS: Age, sex, country of origin and period of residence in Spain, and the results for HIV, hepatitis B, hepatitis C and syphilis. We calculated the proportions in which a serological test had been requested, and examined the association between the rates of positive tests and the geographical area of origin, and calculated age-adjusted rates taking the age distribution of the native population as the reference. RESULTS: Risk of HBV was 4.6 times higher in immigrants than in natives (11.7 times in sub-Saharan Africans). The rate of positive syphilis tests was three times higher in the immigrant group. For HIV the PR was 2.3 (sub-Saharan Africans 7.4). For hepatitis C the risk was lower in immigrants than in natives (PR=0.4). CONCLUSIONS: Immigrants have a higher probability of testing positive in screening in hepatitis B, syphilis and HIV. The rates differ significantly according to the origin of the immigrant.