Emergence of Urease-Negative Klebsiella pneumoniae ST340 Carrying an IncP6 Plasmid-Mediated blaKPC-2 Gene.

An unusual biotype of KPC-2-producing Klebsiella pneumoniae (KPC-Kpn) isolates was detected in Corrientes, Argentina, which, to their isolation date, had been free of KPC-Kpn outbreaks. Our aim was to describe the clinical epidemiology focused on genomic characterization of atypical urease-negative KPC-Kpn clinical isolates belonging to the high-risk hospital-associated clonal lineage ST340/CC258. Thirteen isolates were recovered, all of them from inpatients with KPC-Kpn infection (August 2015 to January 2016). These isolates displayed identical enterobacterial repetitive intergenic consensus-PCR electropherotype belonging to a single clonal sequence type ST340. Whole genome sequencing was performed on two KPC-Kpn and the resistome analyses revealed the following acquired resistance genes: blaKPC-2, blaCTX-M-15, blaOXA-1, blaSHV-11, aac(3)-IId, aph(3')-Ia, aac(6')-Ib-cr, sul1, dfrA14, catB3, fosA, and arr-3. Mutations in GyrA (S83I) and ParC (S80I) were also identified. Among the virulence determinants, yersiniabactin was detected in both strains, specifically the ybt9 locus located in ICEKp3. Five plasmid incompatibility groups were observed in this clone and an unusual IncP6 plasmid bearing blaKPC-2 gene (named pKpn3KP) was fully characterized. In this study, we present the first draft genome sequences of two clinical isolates of KPC-2/CTX-M-15-producing K. pneumoniae belonging to the high-risk clonal lineage ST340/CC258 associated with nosocomial outbreaks in Argentina.

Validación de un instrumento para evaluar condicionantes de género y anticoncepción en adolescentes en Argentinas / Validation of an instrument to evaluate gender conditioners and contraception in Argentine adolescents

INTRODUCCIÓN: A pesar de las políticas y programas puestos en marcha, las estadísticas argentinas registran un alto número de nacimientos provenientes de embarazos en la población adolescente. Para explorar la relación entre los condicionantes de género, la conducta y la salud sexual adolescente, el presente estudio buscó validar un cuestionario de condicionantes de género y anticoncepción (Cogant) desarrollado en España. MÉTODOS: Se realizó un estudio observacional de corte transversal para evaluar la validez y las propiedades psicométricas del Cogant en adolescentes argentinas. RESULTADOS: Se incluyó a 657 mujeres menores de 20 años, que participaron de talleres educativos en el ámbito público de las provincias de Chaco, Corrientes y Buenos Aires. La consistencia interna global del instrumento mostró una alta confiabilidad (alfa de Cronbach 0,857). El análisis de factores sugirió la retención de 7 factores subyacentes, que explican un 61,6% de la varianza del cuestionario. DISCUSIÓN: La evaluación de las medidas psicométricas del Cogant en Argentina mostró resultados similares a los encontrados en las adolescentes españolas, aunque se retuvieron menor cantidad de factores que en el estudio original. El Cogant podría ayudar a identificar las características de los comportamientos vinculados a la sexualidad, al embarazo no planificado y a la maternidad, a fin de que el personal de salud priorice las estrategias de educación y de cuidados para las adolescentes argentinas.

Iron Availability Compromises Not Only Oligodendrocytes But Also Astrocytes and Microglial Cells.

When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination. To better understand myelin formation and OLG maturation, in vivo and in vitro studies were conducted to evaluate the effect of iron deficiency (ID) not only on OLG maturation but also on astrocytes (AST) and microglial cells (MG). In vivo experiments in an ID model were carried out to describe maturational events during OLG and AST development and the reactive profile of MG during myelination when iron availability is lower than normal. In turn, in vitro assays were conducted to explore proliferating and maturational states of each glial cell type derived from control or ID conditions. Studies targeted NG2, PDGFRα, CNPAse, CC1, and MBP expression in OLG, GFAP and S100 expression in AST, and CD11b, ED1, and cytokine expression in MG, as well as BrDU incorporation in the three cell types. Our results show that ID affected OLG development at early stages, not only reducing their maturation capacity but also increasing their proliferation and affecting their morphological complexity. AST ID proliferated more than control ones and were more immature, much like OLG. Cytokine expression in ID animals reflected an anti-inflammatory state which probably influenced OLG maturation. These results show that ID conditions alter all glial cells and may impact myelin formation, which could be regulated by a mechanism involving a cross talk between AST, MG, and oligodendrocyte progenitors (OPC).

Infección urinaria por enterobacterias multirresistentes en un centro de trasplante renal / Urinary Tract Infection by Multiresistant Enterobacteriaceae in a Renal Transplant Center

La infección bacteriana del tracto urinario (ITU) es la cau-sa más frecuente de complicación en el paciente trasplantado renal. Nuestros objetivos fueron determinar los patógenos mas frecuentes, su asociación al tiempo transcurrido al primer episodio de ITU, los factores de riesgo predisponentes y la sensibilidad antibiótica de los gérmenes.Materiales y Métodos: se realizó un estudio retrospectivo en el que se siguió por un año a los pacientes trasplantados renales entre noviem-bre de 2006 a febrero de 2012. Se incluyó el primer urocultivo positivo con bacilos gram negativos. Resultados: de 156 pacientes analizados, 63 (40 %) tuvieron al menos un episodio de ITU en el que se caracterizaron los microorganismos responsables. El patógeno más frecuente fue Klebsiella pneumoniae(25/63 episodios, 39 %), seguido por Escherichia coli (23/63, 37 %). Casi la mitad (31/63, 49 %) ocurrieron antes de los 30 días (58 % por K. pneu-moniae), un tercio (18/63, 29 %) entre los 31 y 180 días (39 % por E. coli) y el resto (14/63, 22 %) en el medio año siguiente (64 % de ellas cau-sadas por E. coli). Entre las K. pneumoniae, 22/25 (88 %) resultaron productoras de ß lactamasas de espectro extendido. Como factores de riesgo predisponentes se encontraron sexo femenino, litiasis renal previa y utilización de catéter doble J. Conclusión: este estudio confirma que las ITU son una complicación frecuente en los transplantados renales. La asociación de K. pneumo-niae multirresistentes con las infecciones inmediatas puede ser consi-derada como marcadora de infección intrahospitala-ria, y señala la posibilidad de realizar intervenciones que modifiquen su incidencia

Urinary tract infections (UTI) are the most frequent complication in renal transplant patients. Our aims were to determine the most common pathogens, the association of different enterobacterias with the time of the onset of the infection, the impact of several risk factors and antibiotic susceptibility.Materials and Methods: The patients were monitored for a year after the renal transplant from November 2006 to February 2012. A retrospective analysis was done and the first positive urine culture with gram negative bacilli was included.Results: From a total of 156 patients analyzed, 63 (40%) had at least one experience of UTI in which the responsible microorganisms were characterized. The most common pathogen was Klebsiella pneumoniae (25/63 episodes, 39 %), followed by Escherichia coli (23/63, 37 %). Almost half of the cases (31/63, 49%) occurred within 30 days (58% for K. pneumoniae), one third of them (18/63, 29%) between 31 and 180 days (39% for E. coli) and the remainings (14/ 63, 22%) in the next half year (64% of them caused by E. coli). Most of the K. pneumoniae, (22/25, 88%) were extended spectrum ß lactamases producers. We can mention as predisposing risk factors: female gender, lithiasis and urinary stent presence. Conclusion: This study confirms that UTIs are a frequent complication in renal transplantation. The association of multiresistant K. pneumoniae infections with immediate UTI can be considered as a marker of nosocomial infection, and points out intervention as a possibility to modify this impact

Blood pressure and cognition among older adults: a meta-analysis.

Hypertension has adverse effects on cognition, can alter cerebral vasculature integrity, and is associated with the pathogenesis of dementia. Using meta-analysis, we correlated blood pressure to multiple cognitive domains among older adults free of clinical stroke and dementia. We identified 230 studies indexed in PubMed and PsycINFO relating blood pressure and cognition. After applying exclusion criteria, we selected n = 12 articles with n = 4,076 participants (age range 43-91 years). Meta-analysis yielded an association between blood pressure and episodic memory (r = -.18, p < .001) and between blood pressure and global cognition (r = -.07, p < .001). When limiting analyses to studies adjusting for vascular covariates (n = 8, n = 2,141), blood pressure was modestly related to global cognition (r = -.11, p < .001), attention (r = .14, p = .002), and episodic memory (r = -.20, p < .001) with a trend for language (r = -.22, p = .07). Findings underscore the need to manage blood pressure as a key prevention method in minimizing abnormal cognitive aging prior to the onset of clinical dementia.

Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-α and serologic autoimmunity in lupus patients.

Increased IFN-α signaling is a heritable risk factor for systemic lupus erythematosus (SLE). IFN induced with helicase C domain 1 (IFIH1) is a cytoplasmic dsRNA sensor that activates IFN-α pathway signaling. We studied the impact of the autoimmune-disease-associated IFIH1 rs1990760 (A946T) single nucleotide polymorphism upon IFN-α signaling in SLE patients in vivo. We studied 563 SLE patients (278 African-American, 179 European-American, and 106 Hispanic-American). Logistic regression models were used to detect genetic associations with autoantibody traits, and multiple linear regression was used to analyze IFN-α-induced gene expression in PBMCs in the context of serum IFN-α in the same blood sample. We found that the rs1990760 T allele was associated with anti-dsDNA Abs across all of the studied ancestral backgrounds (meta-analysis odds ratio = 1.34, p = 0.026). This allele also was associated with lower serum IFN-α levels in subjects who had anti-dsDNA Abs (p = 0.0026). When we studied simultaneous serum and PBMC samples from SLE patients, we found that the IFIH1 rs1990760 T allele was associated with increased IFN-induced gene expression in PBMCs in response to a given amount of serum IFN-α in anti-dsDNA-positive patients. This effect was independent of the STAT4 genotype, which modulates sensitivity to IFN-α in a similar way. Thus, the IFIH1 rs1990760 T allele was associated with dsDNA Abs, and in patients with anti-dsDNA Abs this risk allele increased sensitivity to IFN-α signaling. These studies suggest a role for the IFIH1 risk allele in SLE in vivo.

IgA anti-beta2-glycoprotein I autoantibodies are associated with an increased risk of thromboembolic events in patients with systemic lupus erythematosus.

BACKGROUND: The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-beta2-glycoprotein I (isolated IgA anti-beta2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-beta2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-beta2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-beta2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-beta2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin). CONCLUSIONS/SIGNIFICANCE: The presence of isolated IgA anti-beta2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-beta2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity.

Oligodendrogenesis: the role of iron.

Iron seems to be an essential factor in myelination and oligodendrocyte (OLGc) biology. However, the specific role of iron in these processes remains to be elucidated. Iron deficiency (ID) imposed to developing rats has been a relevant model to understand the role of iron in oligodendrogenesis and myelination. During early development ID causes specific changes in myelin composition, including a lower relative content of cholesterol, proteolipid protein (PLP), and myelin basic protein 21 (MBP21). These changes could be a consequence of the adverse effects of ID on OLGc development and function. We subsenquently studied the possible corrective effect of a single intracranial injection (ICI) of apotransferrin (aTf) on myelin formation in ID rats OLGc migration and differentiation after an ICI of aTf was evaluated at 3 days of age. ID increased the number of proliferating and undifferentiated cells in the corpus callosum (CC), while a single aTf injection reverts these effects, increasing the number of mature cells and myelin formation. Overall, results of a series of studies supports the concept that iron may affect OLGc development at early stages of embryogenesis rather than during late development. Myelin composition is altered by a limited iron supply, changes that can be reverted by a single injection of aTf.

Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

BACKGROUND: Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. CONCLUSIONS/SIGNIFICANCE: Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

Ocrelizumab: a step forward in the evolution of B-cell therapy.

Recent advances in our understanding of B-cell dysregulation and its important link to autoimmunity have brought about a radical change in the management of autoimmune diseases. Over the past few years, encouraging data from several clinical trials of rituximab, a chimeric anti-CD20 antibody, have led to its approval for use in rheumatoid arthritis (RA). These data, regarding clinical efficacy, safety, improved patient-reported outcomes and cost-effectiveness with the use of rituximab in patients with RA, have led to the exploration of other agents targeting B-cell functions. Ocrelizumab, a novel humanized anti-CD20 antibody, has shown clinical efficacy and safety in a recently reported trial in patients with RA. Future clinical trials will help evaluate further the role of ocrelizumab in RA and its potential use in other autoimmune diseases. This review describes current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab as a B-cell-targeted therapy.