Relentless increase of resistance to fluoroquinolones and expanded-spectrum cephalosporins in Escherichia coli: 20 years of surveillance in resource-limited settings from Latin America.

AbstractPrevious studies on commensal Escherichia coli from healthy children in the Bolivian Chaco have shown remarkable resistance rates to the old antibiotics since the early 1990s, and the emergence of resistance to newer drugs (fluoroquinolones and expanded-spectrum cephalosporins) in the 2000s. Here we report the results of a new survey conducted in 2011 in the same setting. Rectal swabs were obtained from 482 healthy children (aged 6–72 months) from three urban areas of the Bolivian Chaco. Screening for antibiotic-resistant E. coli was performed by a direct plating method, as in the previous studies. The blaCTX-M genes were investigated by PCR/sequencing, and CTX-M-producing isolates were subjected to genotyping and detection of several plasmid-mediated quinolone resistance mechanisms. Results showed high rates of resistance to nalidixic acid (76%), ciprofloxacin (44%) and expanded-spectrum cephalosporins (12.4%), demonstrating a relentless increase of resistance to those drugs over the past two decades. CTX-M-type extended-spectrum beta-lactamases were found to be widespread (12%, 97% of extended-spectrum beta-lactamase producers). Compared with the previous studies, CTX-M-producing E. coli underwent a dramatic dissemination (120-fold increase since early 2000s) and a radical change of dominant CTX-M groups (CTX-M-1 and CTX-M-9 groups versus CTX-M-2 group). Most CTX-M producers were not susceptible to quinolones (91%), and 55% carried plasmid-mediated quinolone resistance genes (different combinations of aac(6')-Ib-cr, qnrB and qepA). This study shows the rapid and remarkable increasing trend for resistance to fluoroquinolones and expanded-spectrum cephalosporins in one of the poorest regions of Latin America, and underscores the need for urgent control strategies aimed at preserving the efficacy of those drugs in similar settings

Might some gamma ray bursts be an observable signature of natural wormholes?

The extragalactic microlensing scenario for natural wormholes is examined. It is shown that the main features of wormhole lensing events upon the light of distant Active Galactic Nuclei (AGNs) are similar to some types of already observed Gamma Ray Bursts (GRBs). Using recent satellite data on GRBs, an upper limit to the negative mass density -- ${\cal O} (10^{-36})$ g cm$^{-3}$ -- under the form of wormhole-like objects is presented.Comment: extended version, additions on GRB physics, background sources and cosmological consequences. Two ps figures. Accpeted for publication in Phys. Rev.

Unsharp Quantum Reality

The positive operator (valued) measures (POMs) allow one to generalize the notion of observable beyond the traditional one based on projection valued measures (PVMs). Here, we argue that this generalized conception of observable enables a consistent notion of unsharp reality and with it an adequate concept of joint properties. A sharp or unsharp property manifests itself as an element of sharp or unsharp reality by its tendency to become actual or to actualize a specific measurement outcome. This actualization tendency-or potentiality-of a property is quantified by the associated quantum probability. The resulting single-case interpretation of probability as a degree of reality will be explained in detail and its role in addressing the tensions between quantum and classical accounts of the physical world will be elucidated. It will be shown that potentiality can be viewed as a causal agency that evolves in a well-defined way

Long-Standing International Cooperation in Parasitology Research: A Summary of 35 Years of Activities in the Bolivian Chaco

The Bolivian Chaco is a semiarid region with a low population density, situated in the southeast part of the Plurinational State of Bolivia. Here, despite the improvements of the last 15 years, poverty remains high in rural areas, where social vulnerability is widespread. The Guaraní ethnic group often lives in isolated communities with a low standard of hygiene and sanitation. This epidemiological scenario favors the spread of transmissible diseases, including several parasitic infections belonging to the neglected tropical diseases (NTDs) group. In this area, a long-standing research activity, built upon the synergism between local and foreign institutions, has been established since the late 1980s and helps to fill in the knowledge gap about the epidemiology dynamics of soil-transmitted helminths, vector-borne parasites, and other parasitic diseases. A 35-year history of cooperation programs in parasitology research has contributed to informing local health authorities of the NTD burden in the Bolivian Chaco and, ultimately, supports local healthcare providers in the management of parasitic diseases

Chagas disease in Italy: breaking an epidemiological silence

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Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness

Contains fulltext : 89797.pdf (publisher's version ) (Closed access)OBJECTIVE: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC. PATIENTS AND METHODS: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: 75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined. RESULTS: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease. CONCLUSIONS: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.01 december 201

Somatic mutations of KIT in familial testicular germ cell tumours

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino acid substitutions in exon 17 and one was a 12bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with 3 out 116 unilateral cases (p = 0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes

Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis

Thymidine phosphorylase is an angiogenic factor primarily expressed by cancer cells, stromal cells and tumour-associated macrophages in many human malignancies. These different types of thymidine phosphorylase-expressing cells, however, may have a distinct place in the angiogenic process, and this question was addressed in the present study. A series of 20 normal/hyperplastic prostate glands and 60 prostate carcinomas was investigated by immunohistochemistry, using specific antibodies for thymidine phosphorylase (P-GF.44C), tumour-associated macrophages (CD68), endothelium (CD31) and prostate specific antigen (ER-PR8). Thymidine phosphorylase expression by normal and hyperplastic epithelial or stromal cells occurred almost exclusively in the context of an intense lymphocytic infiltrate. High thymidine phosphorylase cancer cells and thymidine phosphorylase stromal cells expression was associated with high angiogenesis in prostate carcinomas, and this significant association was extended to include both tumour-associated macrophages and tumour-infiltrating lymphocytes. Thymidine phosphorylase expression and tumour-infiltrating lymphocytes were related inversely with prostate specific antigen reactivity. In conclusion, thymidine phosphorylase is a major angiogenic factor in prostate carcinomas and its up-regulation is likely to occur in the context of a host immune response

ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors

<p>Abstract</p> <p>Background</p> <p>Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.</p> <p>Methods</p> <p>ADAMTS1 was downregulated by shRNA technology in the human prostate cancer cell line LNCaP (androgen-dependent), originally expressing ADAMTS1, and was upregulated by transfection in its subline LNCaP-19 (androgen-independent), expressing low levels of ADAMTS1. Cells were implanted subcutaneously in nude mice and tumor growth, microvessel density (MVD), blood vessel morphology, pericyte coverage and thrombospondin 1 (TSP1) were studied in the tumor xenografts.</p> <p>Results</p> <p>Modified expression of ADAMTS1 resulted in altered blood vessel morphology in the tumors. Low expression levels of ADAMTS1 were associated with small diameter blood vessels both in LNCaP and LNCaP-19 tumors, while high levels of ADAMTS1 were associated with larger vessels. In addition, TSP1 levels in the tumor xenografts were inversely related to ADAMTS1 expression. MVD and pericyte coverage were not affected. Moreover, upregulation of ADAMTS1 inhibited tumor growth of LNCaP-19, as evidenced by delayed tumor establishment. In contrast, downregulation of ADAMTS1 in LNCaP resulted in reduced tumor growth rate.</p> <p>Conclusions</p> <p>The present study demonstrates that ADAMTS1 is an important regulatory factor of angiogenesis and tumor growth in prostate tumors, where modified ADAMTS1 expression resulted in markedly changed blood vessel morphology, possibly related to altered TSP1 levels.</p