Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

Evaluation of the Osteogenic Potential of Growth Factorâ Rich Demineralized Bone Matrix In Vivo

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141502/1/jper0036.pd

Joint Arthroplasties other than the Hip in Solid Organ Transplant Recipients

Transplantation Surgery has undergone a great development during the last thirty years and the survival of solid organ recipients has increased dramatically. Osteo-articular diseases such as osteoporosis, fractures, avascular bone necrosis and osteoarthritis are relatively common in these patients and joint arthroplasty may be required. The outcome of hip arthroplasty in patients with osteonecrosis of the femoral head after renal transplantation has been studied and documented by many researchers. However, the results of joint arthroplasties other than the hip in solid organs recipients were only infrequently reported in the literature. A systematic review of the English literature was conducted in order to investigate the outcome of joint arthroplasties other than the hip in kidney, liver or heart transplant recipients. Nine pertinent articles including 51 knee arthroplasties, 8 shoulder arthroplasties and 1 ankle arthroplasty were found. These articles reported well to excellent results with a complication rate and spectrum comparable with those reported in nontransplant patients

The Challenges, Opportunities, and Imperative of Structured Reporting in Medical Imaging

Despite dramatic innovation in medical imaging and information system technologies, the radiology report has remained stagnant for more than a century. Structured reporting was created in the hopes of addressing well-documented deficiencies in report content and organization but has largely failed in its adoption due to concerns over workflow and productivity. A number of political, economical, and clinical quality-centric initiatives are currently taking place within medicine which will dramatically change the medical landscape including Pay for Performance, Evidence-Based Medicine, and the Physician Quality Reporting Initiative. These will collectively enhance efforts to improve quality in reporting, stimulate new technology development, and counteract the impending threat of commoditization within radiology. Structured reporting offers a number of unique opportunities and advantages over traditional free text reporting and will provide a means for the radiology community to add value to its most important service deliverable the radiology report

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease

Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20×106 sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkin's disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation

Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice

Background: It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated.Methods: In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21.Results: We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-γ (IFN-γ) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-α (TNF-α) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness.Conclusion: Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD

Species' geographic distributions through time: Playing catchup with changing climates

This is the author's accepted manuscript.Species’ ranges are often treated as a rather fixed characteristic, rather than a fluid, ever-changing manifestation of their ecological requirements and dispersal abilities. Paleontologists generally have had a more flexible point of view on this issue than neontologists, but each perspective can improve by appreciating the other. Here, we provide an overview of paleontological and neontological perspectives on species’ geographic distributions, focusing on what can be learned about historical variations in distributions. The cross-disciplinary view, we hope, offers some novel perspectives on species-level biogeography

Determinants of participation in colonoscopic screening by siblings of colorectal cancer patients in France

International audienceBACKGROUND: Targeted colonosocopic screening is recommended for first-degree relatives of colorectal cancer patients diagnosed before the age of 60 and offers the possibility of reducing morbidity and mortality, but participation remains too low. The objective of this study was to determine in a French population the factors that affect siblings' participation in screening, notably those relating to the individuals, their medical care, their family and their social network. METHODS: A cross sectional survey was conducted in siblings of index patients having undergone surgery for colorectal cancer between 1999 and 2002 in two French counties. Siblings were contacted during 2007 and 2008 through the index patient. The factors affecting participation in colonoscopic screening were studied by logistic regression taking into account family cluster effect. RESULTS: 172 siblings of 74 index cases were included. The declared rate of undergoing at least one colonoscopy among siblings was 66%; 95%CI 59-73%. Five variables were independently associated with colonoscopic screening: perceiving fewer barriers to screening (OR = 3.2; 95%CI 1.2-8.5), having received the recommendation to undergo screening from a physician (OR = 4.9; 1.7-13.7), perceiving centres practising colonoscopy as more accessible (OR = 3.2, 1.3-7.8), having discussed screening with all siblings (OR = 3.9; 1.6-9.6) and being a member of an association (OR = 2.6; 1.0-6.6). CONCLUSIONS: The factors independently associated with participation in CRC screening by an individual at increased risk belonged to each of four dimensions relating to his individual psychosocial characteristics, to his relationship with a physician, within the family and social environment. The relevance of these results to clinical practice may help to improve compliance to recommendations in a global preventive strategy including all stages of the information pathway from the physician to the index patient and his relatives

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012