Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Revision Medial Patellofemoral Ligament Reconstruction for Recurrent Instability After Patellofemoral Arthroplasty

Recurrent patellar instability is a rare complication after patellofemoral arthroplasty (PFA) and usually involves a traumatic injury. Medial patellofemoral ligament (MPFL) reconstruction after arthroplasty is a complicated and technically challenging surgical procedure because the lack of patellar bone stock due to resurfacing significantly increases the risk of patellar fracture. We present our surgical technique for revision MPFL reconstruction for recurrent instability after PFA. This technical note describes the use of 1.8-mm all-suture anchors for revision MPFL reconstruction in patients with decreased patellar bone stock after PFA. This technique reduces the risk of patellar fracture without compromising the integrity of the MPFL graft

Structure elucidation of capsular polysaccharides from Streptococcus pneumoniae serotype 33C, 33D, and revised structure of serotype 33B

We report herein the previously unknown structures of the pneumococcal capsular polysaccharides serotype 33C and 33D, and a revised structure of serotype 33B. The syntenic pair 33B/33D has nearly identical polysaccharide repeat units with the exception of one sugar residue (\u21922-\u3b1-Glcp in 33B and \u21922-\u3b1-Galp in 33D). Serotype 33C is structurally more similar to 33B/33D than 33A/33F, in that it also possesses a backbone ribitol-phosphate group and a \u21923-\u3b2-GalpNAc residue, both of which are absent in the repeat units of 33A/33F. Serotype 33C is notably different from all other serogroup 33 polysaccharides, as there is no \u21923-\u3b2-Glcp residue and the location of the O-acetylation of the \u21925-\u3b2-Galf residue (O-6) differs from the other serogroup 33 polysaccharides (O-2). This completes the structural assignments of polysaccharides within serogroup 33 and provides a framework for understanding the recognition of epitopes by serogroup 33 typing sera based on observed cross-reactivities reported in the literature. \ua9 2013 Elsevier Ltd. All rights reserved.Peer reviewed: YesNRC publication: Ye

Cough receptor sensitivity in children with acute and non-acute asthma

BACKGROUND: Cough is a major symptom in some children with asthma. The relationship between cough and the severity of asthma is ill defined. A study was undertaken to test the hypotheses that, in children with asthma who cough as a major part of their asthma symptoms, cough receptor sensitivity (CRS) is heightened during an acute severe exacerbation of asthma but not in the non-acute phase and airway calibre or its change correlates with CRS. METHODS: Spirometric measurements and the capsaicin CRS test were performed on children admitted to hospital for an acute severe exacerbation of asthma. Nasal secretions were tested for viruses. The children were grouped into those who usually cough with asthma episodes and those who do not. The tests were repeated 7-10 days and 4-6 weeks later. The CRS outcome measure used was the concentration of capsaicin required to stimulate two (Cth) and five coughs (C5). RESULTS: The CRS of the group who coughed (n = 15) was significantly higher than those who did not cough (n = 16) (mean difference log Cth 0.77 mumol (95% CI 0.35 to 1.18), C5 0.72 mumol (95% CI 0.26 to 1.18)) during acute asthma but not after the exacerbation. CRS was not significantly different between groups based on the presence of a viral infection. Neither forced expiratory volume in one second (FEV1) nor its change correlated with CRS nor its change. CONCLUSIONS: In children with asthma CRS is heightened in acute severe asthma in the subgroup of children who have cough as a significant symptom with their asthma episodes. In acute and non-acute asthma CRS does not correlate with FEV1. 



The future of zoonotic risk prediction

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’