Association of polymorphisms in leptin and adiponectin genes with long-term outcomes in renal transplant recipients.

The effect of polymorphims in leptin and adiponectin genes on long-term outcomes of renal transplantation is unknown. In 349 renal transplant recipients (RTR), we aimed to determine associations between five SNPs in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes and these outcomes. Follow-up time ranged from 2 to 25 years (mean 10.29 ± 5.16 years). Two SNPs showed associations with long-term outcomes and their statistical significance greatly increased after 39 RTR with a history of cardiovascular events prior to transplantation were removed from the analysis. Adjusted odds ratios (OR) for LEPR rs1805094 and ADIPOQ rs1501299 and risk of graft loss were 0.35 (0.16-0.74) p = 0.006 and 2.37 (1.28-4.37) p = 0.006, respectively. The assessment of risk for global mortality revealed OR values of 0.20 (0.06-0.62), p = 0.005, and 2.43 (1.08-5.44), p = 0.031 for LEPR rs1805094 and ADIPOQ rs1501299, respectively. Our results show that polymorphism in genes involved in leptin and adiponectin function modify long-term outcomes in renal transplantation.

Body Fat Distribution, Adipocytokines Levels and Variability in Associated Genes and Kidney Transplant Outcomes.

Introduction: Body fat distribution is known to contribute to a variety of pathologies. Research Questions: We aimed to assess whether this distribution is associated with clinical outcomes in renal transplant recipients (RTR) and to examine its relationship with leptin and adiponectin gene variants and plasma concentrations. Design: Bioelectrical impedance analyses were performed in 236 RTR. Leptin/adiponectin levels were measured by immunoassay and relevant polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes were identified. Associations were assessed by logistic regression modeling. Results: The waist-to-height ratio (WHr) displayed a significant association with delayed graft function, acute rejection and post-transplant diabetes mellitus, with OR values of 2.04 (1.02-4.08) p = 0.045; 3.08 (1.22-7.79) p = 0.017 and 2.79 (1.16-6.74) p = 0.022, respectively. Waist circumference was linked to delayed graft function [OR = 1.03 (1.01-1.05), p = 0.025] and AR [OR = 1.041 (1.01-1.07), p = 0.009]. Leptin levels were significantly higher in patients who experienced rejection [19.91 ± 23.72 versus 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01-1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs 96.38 ± 14.65 for GG/GT genotypes; p = 0.021). Conclusion: WC, and especially WHr, are associated with adverse outcomes in renal transplantation and are affected by variability in the ADIPOQ gene.

Characterization of the Differential Pathogenicity of Candida auris in a Galleria mellonella Infection Model.

Candida auris is an emergent multidrug-resistant fungal pathogen considered a severe global threat due to its capacity to cause nosocomial outbreaks and deep-seated infections with high transmissibility and mortality. However, evidence on its pathogenicity and the complex host-pathogen interactions is still limited. This study used the in vivo invertebrate model in Galleria mellonella to assess its virulence, exploring the mortality kinetics, melanization response, and morphological changes after fungal infection compared to Candida albicans and Candida parapsilosis, with known high and low pathogenicity, respectively. All C. auris isolates presented less virulence than C. albicans strains but higher than that induced by C. parapsilosis isolates. Increased pathogenicity was observed in nonaggregative phenotypes of C. auris, while the melanization response of the larvae to fungal infection was homogeneous and independent of the causing species. C. auris was able to filament in the in vivo animal model G. mellonella, with aggregative and nonaggregative phenotypes presenting various pseudohyphal formation degrees as pathogenicity determinants in a strain-dependent manner. Histological invasiveness of C. auris mimicked that observed for C. albicans, with effective dissemination since the early stages of infection both in yeast and filamented forms, except for a remarkable respiratory tropism not previously observed in other yeasts. These characteristics widely differ between strains and advocate the hypothesis that the morphogenetic variability of C. auris is an indicator of its flexibility and adaptability, contributing to its emergence and rising worldwide prevalence. IMPORTANCE Candida auris is an emergent fungus that has become a global threat due to its multidrug resistance, mortality, and transmissibility. These unique features make it different from other Candida species, but we still do not fully know the degree of virulence and, especially, the host-pathogen interactions. In this in vivo insect model, we found that it presents an intermediate degree of virulence compared to known high- and low-virulence Candida species but with significant variability between aggregative and nonaggregative strains. Although it was previously considered unable to filament, we documented in vivo filamentation as an important pathogenic determinant. We also found that it is able to disseminate early through the host, invading both the circulatory system and many different tissues with a remarkable respiratory tropism not previously described for other yeasts. Our study provides new insights into the pathogenicity of an emergent fungal pathogen and its interaction with the host and supports the hypothesis that its morphogenetic variability contributes to its rising global prevalence.

Staphylococcus aureus pathogenicity island DNA is packaged in particles composed of phage proteins.

Staphylococcus aureus pathogenicity islands (SaPIs) have an intimate relationship with temperate staphylococcal phages. During phage growth, SaPIs are induced to replicate and are efficiently encapsidated into special small phage heads commensurate with their size. We have analyzed by amino acid sequencing and mass spectrometry the protein composition of the specific SaPI particles. This has enabled identification of major capsid and tail proteins and a putative portal protein. As expected, all these proteins were phage encoded. Additionally, these analyses suggested the existence of a protein required for the formation of functional phage but not SaPI particles. Mutational analysis demonstrated that the phage proteins identified were involved only in the formation and possibly the function of SaPI or phage particles, having no role in other SaPI or phage functions.

[Prevalence of obesity and cardiovascular risk in the general population of a health area in Extremadura (Spain): the Hermex study]. / Prevalencia de obesidad y riesgo cardiovascular asociado en la población general de un área de salud de Extremadura. Estudio Hermex.

INTRODUCTION AND OBJECTIVES: To estimate the prevalence of obesity and its associated cardiovascular risk in the general population of a health area in Extremadura. MATERIALS AND METHODS: A cross-sectional study on a random population sample aged 25-79 years from the Don Benito-Villanueva (Badajoz) health area. Risk factors and cardiovascular disease were examined. Anthropometric and blood pressure measurements were collected, and a blood sample was taken. Obese subjects were categorized into different risk levels as proposed by the Spanish Society for the Study of Obesity, and the influence of obesity on estimation of the risk of ischemic heart disease was studied using the Framingham function, as adapted for Spain. RESULTS: A total of 2833 of the 3521 subjects screened (80.5%) participated in the study. Mean age was 51.2 years (SD 14.7), and 46.5% were males. Male subjects had a greater prevalence of overweight and obesity (46.2% and 37.7% respectively) as compared to females (37.7% and 32.6%) (p<0.005 and p<0.05 respectively). Only 10% of obese subjects had no increased cardiovascular risk. Obesity was associated to an 8-fold increase in the presence of a high risk for ischemic heart disease in females (p<0.001), as compared to a 1.4-fold increase in males (p=0.095). CONCLUSIONS: Obesity is highly prevalent and affects, together with overweight, 74.1% of the population in an Extremadura health area. A vast majority of obese subjects have an increased cardiovascular risk, which is very marked for ischemic heart disease in females.

SaPI mutations affecting replication and transfer and enabling autonomous replication in the absence of helper phage.

The SaPIs are chromosomal islands in staphylococci and other Gram-positive bacteria that carry genes for superantigens, virulence factors, resistance and certain metabolic functions. They have intimate relationships with certain temperate phages involving phage-induced excision, replication and efficient packaging in special small-headed infective phage-like particles, resulting in very high transfer frequencies. They generally contain 18-22 ORFs. We have systematically inactivated each of these ORFs and determined their functional groupings. In other reports, we have shown that five are involved in excision/integration, replication and packaging. In this report, we summarize the mutational analysis and focus on two key ORFs involved in regulation of the SaPI excision-replication-packaging cycle vis-à-vis phage induction. These two genes are divergently transcribed and define the major transcriptional organization of the SaPI genome. One of them, stl, encodes a master repressor, possibly analogous to the standard cI phage repressor. Mutational inactivation of this gene results in SaPI excision and replication in the absence of any inducing phage. This replicated SaPI DNA is not packaged; however, since the capsid components are provided by the helper phage. We have not yet ascertained any specific function for the second putative regulatory gene, though it is highly conserved among the SaPIs.

Role of staphylococcal phage and SaPI integrase in intra- and interspecies SaPI transfer.

SaPIbov2 is a member of the SaPI family of staphylococcal pathogenicity islands and is very closely related to SaPIbov1. Typically, certain temperate phages can induce excision and replication of one or more of these islands and can package them into special small phage-like particles commensurate with their genome sizes (referred to as the excision-replication-packaging [ERP] cycle). We have studied the phage-SaPI interaction in some depth using SaPIbov2, with special reference to the role of its integrase. We demonstrate here that SaPIbov2 can be induced to replicate by different staphylococcal phages. After replication, SaPIbov2 is efficiently encapsidated and transferred to recipient organisms, including different non-Staphylococcus aureus staphylococci, where it integrates at a SaPI-specific attachment site, att(C), by means of a self-coded integrase (Int). Phages that cannot induce the SaPIbov2 ERP cycle can transfer the island by recA-dependent classical generalized transduction and can also transfer it by a novel mechanism that requires the expression of SaPIbov2 int in the recipient but not in the donor. It is suggested that this mechanism involves the encapsidation of standard transducing fragments containing the intact island followed by int-mediated excision, circularization, and integration in the recipient.

SaPI operon I is required for SaPI packaging and is controlled by LexA.

Transfer of Staphylococcus aureus pathogenicity islands (SaPIs) is directly controlled by the cellular repressor LexA. We have found that transcription of the SaPIbov1 operon I is repressed by LexA and is therefore SOS-induced. Two copies of the LexA binding site consensus (Cheo box) are present in the 5' region of this operon, at the same location in all of 15 different SaPIs analysed. Both of these boxes bind LexA protein. Furthermore, replacement of the chromosomal lexA with a non-cleavable mutant LexA (G94E) greatly diminished expression of SaPIbov1 operon I and differentially reduced the production of SaPI transducing particles in comparison with the production of plaque-forming particles. In concordance with this finding, deletion of operon I blocked the formation of SaPI transducing particles but had no effect on replication of the island. Operon I contains a gene encoding a homologue of the phage terminase small subunit plus two other genes that direct the assembly of the small sized SaPIbov1 capsids. Interestingly, mutations affecting the latter two genes were not defective in SaPI transfer, but rather encapsidated the island in full-sized phage heads, which would have to contain a multimeric SaPI genome.

SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development.

Staphylococcus epidermidis biofilm formation is associated with the production of the polysaccharide intercellular adhesin (PIA)--poly-N-acetylglucosamine polysaccharide (PNAG) by the products of the icaADBC operon. Recent evidence indicates that SarA, a central regulatory element that controls the production of Staphylococcus aureus virulence factors, is essential for the synthesis of PIA/PNAG and the ensuing biofilm development in this species. Based on the presence of a sarA homolog, we hypothesized that SarA could also be involved in the regulation of the biofilm formation process in S. epidermidis. To investigate this, we constructed nonpolar sarA deletions in two genetically unrelated S. epidermidis clinical strains, O-47 and CH845. The SarA mutants were completely defective in biofilm formation, both in the steady-state conditions of a microtiter dish assay and in the flow conditions of microfermentors. Reverse transcription-PCR experiments showed that the mutation in the sarA gene resulted in downregulation of the icaADBC operon transcription in an IcaR-independent manner. Purified SarA protein showed high-affinity binding to the icaA promoter region by electrophoretic mobility shift assays. Consequently, mutation in sarA provoked a significant decrease in the amount of PIA/PNAG on the cell surface. Furthermore, heterologous complementation of S. aureus sarA mutants with the sarA gene of S. epidermidis completely restored biofilm formation. In summary, SarA appeared to be a positive regulator of transcription of the ica locus, and in its absence, PIA/PNAG production and biofilm formation were diminished. Additionally, we present experimental evidence showing that SarA may be an important regulatory element that controls S. epidermidis virulence factors other than biofilm formation.

Prevalencia de síndrome metabólico en una población de niños y adolescentes con obesidad / Prevalence of metabolic syndrome in a population of obese children and adolescents

Introducción La obesidad infantil es un problema sanitario creciente y de primer orden para la sociedad, ya que aumenta el riesgo de padecer enfermedades cardiovasculares, diabetes mellitus tipo 2 e hipertensión arterial. Así, cuando los niños obesos se convierten en adultos obesos, los efectos sobre su salud y expectativas de vida pueden ser devastadores.Objetivos1). Determinar la prevalencia de síndrome metabólico (SM) en una población infanto-juvenil con obesidad, y 2). Comparación de parámetros antropométricos y bioquímicos en pacientes con 1 o 2 parámetros de SM frente a los pacientes que cumplen criterios de SM. Material y métodos Estudio transversal descriptivo en niños y adolescentes con obesidad (>p97) tratados en el Servicio de Endocrinología del Hospital de Getafe. Las variables estudiadas fueron: edad, sexo, talla, peso, índice de masa corporal (IMC), circunferencia de cintura (CC), glucemia basal y tras sobrecarga oral de glucosa (SOG), insulinemia, resistencia a la insulina (RI) medida mediante HOMA, triglicéridos (TG), HDL, tensión arterial sistólica y diastólica (TAS y TAD). La definición de SM en adolescentes se hizo de acuerdo a criterios de la International Diabetes Federation (IDF) de 2007.Resultados133 pacientes, 67 varones (50,4%) y 66 mujeres (49,6%), con edad media de 12,17±3,27 años. Todos los pacientes presentaban obesidad superior al p97 para edad y sexo. La prevalencia de los distintos parámetros del SM fue la siguiente: 100% CC>p90 para edad y sexo; 26,08% hipertensión arterial; 15,94% hipertrigliceridemia superior a 150mg/dl; 10,86% HDL < 40mg/dl; 7,97% glucemia en ayunas por encima de 100mg/dl. En conjunto, la prevalencia de SM fue del 19,6%. Cuando comparamos distintos parámetros antropométricos y bioquímicos en los pacientes con 1 o 2 criterios de SM frente a los que presentan SM completo, se observa que a mayor número de criterios de SM, el grado de obesidad y la (..) (AU)

Introduction Childhood obesity is a major and increasing health problem for society because it increases the risk of cardiovascular disease, type 2 diabetes mellitus, and hypertension. Thus, when obese children become obese adults, effects on their health and life expectation may be devastating. Objectives(1) To assess the prevalence of metabolic syndrome (MS) in a child population with obesity and (2) to compare anthropometric and biochemical parameters in patients with one or two parameters of MS syndrome to those of patients who meet MS criteria. Patients and methods A descriptive, cross-sectional study was conducted in children and adolescents with severe obesity (weight >p97) seen at the endocrinology department of Hospital de Getafe. Variables examined included age, sex, height, weight, body mass index (BMI), waist circumference (WC), oral glucose tolerance test (OGTT), insulin, insulin resistance (IR) measured by HOMA, triglycerides (Tg), high density lipoprotein (HDL), and systolic and diastolic blood pressure (SBP and DBP). The definition of MS in adolescents was made according to criteria of the International Diabetes Federation (IDF), 2007.ResultsA total of 133 patients, 67 males (50.4%) and 66 females (49.6%) with a mean age of 12.17±3.27 years, were enrolled into the study. All patients were obese, with a weight greater than the 97h percentile for age and sex. Prevalence of several cardiovascular risk factors was as follows: WC ≥90th percentile for age and sex, 100%; hypertension, 26.08%; hypertriglyceridemia ≥150mg/dL, 15.94%; HDL <40mg/dL, 10.86%; fasting blood glucose levels ≥100mg/dL, 7.97%. The overall prevalence of (..) (AU)

Prevalencia de obesidad y riesgo cardiovascular asociado en la población general de un área de salud de Extremadura. Estudio Hermex / Prevalence of obesity and cardiovascular risk in the general population of a health area in Extremadura (Spain). The Hermex study

Introducción y objetivos Estimar la prevalencia de la obesidad y el riesgo cardiovascular asociado en la población general de un área de salud de Extremadura. Material y métodos Estudio transversal sobre una muestra aleatoria de población entre 25 y 79 años procedente del área de salud de Don Benito-Villanueva (Badajoz). Se estudió la presencia de factores de riesgo y enfermedad cardiovascular. Se recogieron medidas antropométricas, de presión arterial y muestra sanguínea. Se categorizó a la población obesa en distintos niveles de riesgo tal como propone la Sociedad Española para el Estudio de la Obesidad y se estudió la influencia de la obesidad en la estimación del riesgo de cardiopatía isquémica según la función de Framinghan adaptada para España. Resultados De los 3.521 sujetos seleccionados participaron 2.833 (80,5%). La edad media fue 51,2 años (DE 14,7) y el 46,5% fueron hombres. La prevalencia de sobrepeso y obesidad fue superior en hombres (46,2 y 37,7%) con respecto a las mujeres (37,7 y 32,6%) (p<0,005 y p<0,05 respectivamente). Solo el 10% de los obesos no mostraron un riesgo cardiovascular aumentado. La obesidad se asoció a un incremento de presentar riesgo alto de cardiopatía isquémica de 8 veces en la mujer (p<0,001) por 1,4 veces en el hombre (p=0,095).Conclusiones La obesidad es muy prevalente y afecta junto al sobrepeso al 74,1% de la población de un área de salud de Extremadura. La amplia mayoría de los obesos tienen un riesgo cardiovascular aumentado, siendo de gran magnitud para la cardiopatía isquémica en la mujer (AU)

Introduction and objectives To estimate the prevalence of obesity and its associated cardiovascular risk in the general population of a health area in Extremadura. Materials and methods A cross-sectional study on a random population sample aged 25-79 years from the Don Benito-Villanueva (Badajoz) health area. Risk factors and cardiovascular disease were examined. Anthropometric and blood pressure measurements were collected, and a blood sample was taken. Obese subjects were categorized into different risk levels as proposed by the Spanish Society for the Study of Obesity, and the influence of obesity on estimation of the risk of ischemic heart disease was studied using the Framingham function, as adapted for Spain. Results A total of 2833 of the 3521 subjects screened (80.5%) participated in the study. Mean age was 51.2 years (SD 14.7), and 46.5% were males. Male subjects had a greater prevalence of overweight and obesity (46.2% and 37.7% respectively) as compared to females (37.7% and 32.6%) (p<0.005 and p<0.05, respectively). Only 10% of obese subjects had no increased cardiovascular risk. Obesity was associated to an 8-fold increase in the presence of a high risk for ischemic heart disease in females (p<0.001), as compared to a 1.4-fold increase in males (p=0.095).Conclusions Obesity is highly prevalent and affects, together with overweight, 74.1% of the population in an Extremadura health area. A vast majority of obese subjects have an increased cardiovascular risk, which is very marked for ischemic heart disease in females (AU)