Fear of falling in obese women under 50 years of age: a cross-sectional study with exploration of the relationship with physical activity

An understanding of capacity for physical activity in obese populations should help guide interventions to promote physical activity. Fear of falling is a phenomenon reported in the elderly, which is associated with reduced mobility and lower physical activity levels. However, although falls are reportedly common in obese adults, fear of falling and its relationship with activity has not been investigated in younger obese populations. In a cross-sectional study, fear of falling was measured in 63 women aged 18 to 49 years, with mean BMI 42.1 kg/m (SD 10.3) using the Modified Falls Efficacy (MFES), the Consequences of Falling (COF) and the Modified Survey of Activities and Fear of Falling in the Elderly (MSAFFE) scales. The choice of scales was informed by prior qualitative interviews with obese younger women. Physical activity levels were measured at the same time using the International Physical Activity Questionnaire. The mean score for fear of falling scales, with 95% confidence intervals, were estimated. Chi-square tests and t-tests were used to explore differences in age, body mass index and fear of falling scores between fallers and non-fallers. For each fear of falling scale, binomial logistic regression was used to explore its relationship with physical activity. Mean scores suggested high levels of fear of falling: MFES [mean 7.7 (SD 2.7); median 8.5]; COF [mean 31.3 (SD 9.4)]; MSAFFE [mean 25.9 (SD 8.7); median 23]. Scores were significantly worse in fallers (  = 42) compared to non-fallers (  = 21). MFES and MSAFFE were independently associated with lower levels of physical activity [odds ratio = 0.65, 95% Cl 0.44 to 0.96 and odds ratio = 1.14, 95% CI 1.01 to 1.28 respectively], when adjusted for age, BMI and depression. This study confirms that fear of falling is present in obese women under 50 years of age. It suggests that it is associated with low levels of physical activity. These novel findings warrant further research to understand capacity for physical and incidental activity in obese adults in both genders and suggest innovative interventions to promote lifestyle changes and/or consideration of falls prevention in this population

Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis

The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis.

Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis