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BackgroundUrinary tract infections caused by extended-spectrum beta-lactamase producing Enterobacterales (ESBL-EB) are a problem increasing in our clinical practice.ObjectivesThe aim of this study was to evaluate the clinical outcome in patients who received short (≤ 7 days) versus long courses (>7 days) of antimicrobial therapy for complicated ESBL-EB urinary tract infections.MethodsThis is a retrospective and observational study. Positive urine cultures for ESBL-EB in our hospital between March 2015 and July 2017 were identified. Patients with complicated urinary tract infection were included. Differences between treatment groups (7 days or less vs more than 7 days) were analyzed according to baseline characteristics and severity of clinical presentation. Primary outcome was all cause 30-day mortality. Secondary outcome was a combined item of all cause mortality and reinfection by the same enterobacteria at 30 days.Results273 urine cultures were positive for ESBL-EB during the study period. 75 episodes were included, 40 in the long treatment group and 35 in the short treatment group. Mean treatment duration in short and long treatment groups was 6,1 and 13,8 days respectively. Mortality at 30 days was 5,7% in the short treatment group and 5% in the long treatment group without significant differences (P = 0,8). Mortality or reinfection by the same ESBL-EB at 30 days was 8,6% in the short treatment group and 10% in the long treatment group, without significant differences (P = 0,8).ConclusionsShort courses of antimicrobial treatment seems to be effective as treatment of complicated urinary tract infections by ESBL-EB.

INTRODUCTION:Aging is associated with a progressive decrease in bone mass (BM), and being physical active is one of the main strategies to combat this continuous loss. Nonetheless, because daily time is limited, time spent on each movement behavior is co-dependent. The aim of this study was to determine the relationship between BM and movement behaviors in elderly people using compositional data analysis. METHODS:We analyzed 871 older people [395 men (76.9±5.3y) and 476 women (76.7±4.7y)]. Time spent in sedentary behavior (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), was assessed using accelerometry. BM was determined by bone densitometry (DXA). The sample was divided according to sex and bone health indicators. RESULTS:The combined effect of all movement behaviors (PA and SB) was significantly associated with whole body, leg and femoral region BM in the whole sample (p≤0.05), with leg and pelvic BM (p

The Hereditary Spastic Paraplegias (HSP) are a group of heterogeneous disorders with a wide spectrum of underlying neural pathology, and hence HSP patients express a variety of gait abnormalities. Classification of these phenotypes may help in monitoring disease progression and personalizing therapies. This is currently managed by measuring values of some kinematic and spatio-temporal parameters at certain moments during the gait cycle, either in the doctor´s surgery room or after very precise measurements produced by instrumental gait analysis (IGA). These methods, however, do not provide information about the whole structure of the gait cycle. Classification of the similarities among time series of IGA measured values of sagittal joint positions throughout the whole gait cycle can be achieved by hierarchical clustering analysis based on multivariate dynamic time warping (DTW). Random forests can estimate which are the most important isolated parameters to predict the classification revealed by DTW, since clinicians need to refer to them in their daily practice. We acquired time series of pelvic, hip, knee, ankle and forefoot sagittal angular positions from 26 HSP and 33 healthy children with an optokinetic IGA system. DTW revealed six gait patterns with different degrees of impairment of walking speed, cadence and gait cycle distribution and related with patient's age, sex, GMFCS stage, concurrence of polyneuropathy and abnormal visual evoked potentials or corpus callosum. The most important parameters to differentiate patterns were mean pelvic tilt and hip flexion at initial contact. Longer time of support, decreased values of hip extension and increased knee flexion at initial contact can differentiate the mildest, near to normal HSP gait phenotype and the normal healthy one. Increased values of knee flexion at initial contact and delayed peak of knee flexion are important factors to distinguish GMFCS stages I from II-III and concurrence of polyneuropathy.

The aim of this study was to analyze the mortality and predictors of 30-day mortality among hospitalized patients with Pseudomonas aeruginosa urinary tract infection (PAUTI) and the impact of antibiotic treatment on survival.Patients admitted to our hospital with PAUTI or those diagnosed of PAUTI during hospitalization for other disease between September 2012 and September 2014 were included. Repeated episodes from the same patient were excluded. Database with demographic, clinical and laboratory ítems was created. Empirical and definitive antibiotic therapy, antimicrobial resistance and all-cause mortality at 30 and 90 days were included.62 patients were included, with a mean age of 75 years. 51% were male. Mortality was 17.7% at 30 days and 33.9% at 90 days. Factors associated with reduced survival at 30 days were chronic liver disease with portal hypertension (P 3 (P = 0.02) and inadequated definitive antibiotic treatment (P

Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI) and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.

The putative virulence and antimicrobial resistance gene contents of extended spectrum β-lactamase (ESBL)-positive E. coli (n=629) isolated between 2005 and 2009 from humans, animals and animal food products in Germany, The Netherlands and the UK were compared using a microarray approach to test the suitability of this approach with regard to determining their similarities. A selection of isolates (n=313) were also analysed by multilocus sequence typing (MLST). Isolates harbouring bla(CTX-M-group-1) dominated (66%, n=418) and originated from both animals and cases of human infections in all three countries; 23% (n=144) of all isolates contained both bla(CTX-M-group-1) and bla(OXA-1-like) genes, predominantly from humans (n=127) and UK cattle (n=15). The antimicrobial resistance and virulence gene profiles of this collection of isolates were highly diverse. A substantial number of human isolates (32%, n=87) did not share more than 40% similarity (based on the Jaccard coefficient) with animal isolates. A further 43% of human isolates from the three countries (n=117) were at least 40% similar to each other and to five isolates from UK cattle and one each from Dutch chicken meat and a German dog; the members of this group usually harboured genes such as mph(A), mrx, aac(6')-Ib, catB3, bla(OXA-1-like) and bla(CTX-M-group-1). forty-four per cent of the MLST-typed isolates in this group belonged to ST131 (n=18) and 22% to ST405 (n=9), all from humans. Among animal isolates subjected to MLST (n=258), only 1.2% (n=3) were more than 70% similar to human isolates in gene profiles and shared the same MLST clonal complex with the corresponding human isolates. The results suggest that minimising human-to-human transmission is essential to control the spread of ESBL-positive E. coli in humans.

Bacteriophages ϕ29 and Nf from Bacillus subtilis start replication of their linear genomes at both ends using a protein-primed mechanism by means of which the DNA polymerase initiates replication by adding dAMP to the terminal protein, this insertion being directed by the second and third 3' terminal thymine of the template strand, respectively. In this work, we have obtained evidences about the role of the 3' terminal base during the initiation steps of ϕ29 and Nf genome replication. The results indicate that the absence of the 3' terminal base modifies the initiation position carried out by ϕ29 DNA polymerase in such a way that now the third position of the template, instead of the second one, guides the incorporation of the initiating nucleotide. In the case of Nf, although the lack of the 3' terminal base has no effect on the initiation position, its absence impairs further elongation of the TP-dAMP initiation product. The results show the essential role of the 3' terminal base in guaranteeing the correct positioning of replication origins at the polymerization active site to allow accurate initiation of replication and further elongation.