Molecular identification of Sporothrix species in a hyperendemicarea in Peru

To date, there have been no molecular typing studies to identify the Sporothrix species circulating inAbancay, a hyperendemic area of sporotrichosis in Peru. To identify six clinical isolates of the Sporothrixschenckii complex from Abancay, Peru, we used PCR-sequencing of the calmodulin gene, and a phylo-genetic analysis was conducted with these and additional sequences from GenBank. All clinical isolateswere identified as S. schenckii (sensu stricto). Phylogenetic analysis revealed that the six clinical isolatesfrom Abancay, Peru clustered in a clade along with sequences from Costa Rica, Iran, South Africa, and fourother sequences from Peru. These findings reveal the presence of S. schenckii (sensu stricto) in Abancay,Peru.Campus Lima Centr

Solar Drinking Water Disinfection (SODIS) to Reduce Childhood Diarrhoea in Rural Bolivia: A Cluster-Randomized, Controlled Trial

Daniel Maeusezahl and colleagues conducted a cluster-randomized controlled trial in rural Bolivia of solar drinking water disinfection, and find only moderate compliance with the intervention and no evidence of reduction in diarrhea among children

Relation between Epidural Analgesia and severe perineal laceration in childbearing women in Catalonia

Our objectives were to study the association between epidural analgesia and risk of severe perineal laceration (SPL), and identify additional risk factors for SPL. This multicentre study consisted of an analysis of data from the MidconBirth Phase I Database, on the use of EA and perineal results during childbirth. (World Health Organization, International Clinical Trials Registry Platform, 2016: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN17833269). We conducted a prospective study of pregnant women at term between July 2016 and July 2017 in 30 public maternity hospitals in Catalonia, Spain. Inclusion criteria were an uncomplicated singleton pregnancy, in cephalic presentation and vaginal birth. Data was analysed separately for instrumental births and spontaneous vaginal births, as the former is more frequently associated with episiotomy and more perineal lacerations. Risk factors as well as protective factors in each cohort of women (instrumental and spontaneous vaginal birth), were identified. Multivariate logistic regression model was performed to study the association between epidural analgesia and SPL to identify potential confounders. Odds ratios (OR), using 95% confidence intervals (CI) were constructed. During the study period, 5497 eligible women gave birth, 77.46% of them received epidural analgesia. SPL occurred in 1.63% of births. The univariate analysis showed births with epidural analgesia had significantly higher rates of inductions, augmentation of labour, lithotomy position for birth and episiotomy. However, this association disappeared when the variable "type of vaginal birth" was introduced. In multivariate logistic regression, nulliparity was the major predictor for SPL (OR: 0.17; CI 95%: 0.08-0.34, p: 0.000). Epidural analgesia was not associated with SPL once confounding factors were included. Other interesting factors associated with SPL were identified. This paper identifies important practice areas which contribute to SPL and which have the potential to be rectified. It offers evidence on the role that EA plays on pelvic floor injuries and it adds to existing evidence about the disadvantages of using the lithotomy position for birth, especially in relation to SPL. It highlights the need for practice change in Catalonia from what can be considered a medical model of care to one more aligned with the midwifery philosophy of care through the development of clinical guidelines. It also signals the need to provide women with evidence base upon which to make informed choices on the use of EA, specifically in relation to SPL. [Abstract copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Chromosomal instability drives metastasis through a cytosolic DNA response

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC