Citations

AbstractBackgroundRecent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high‐risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined.MethodsA retrospective cohort study of 227 high‐risk first LTR who received primary anti‐CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post‐transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P‐values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant.ResultsCMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end‐stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance.ConclusionOur results suggest that interventions designed to prevent CMV infection and disease should be applied to all high‐risk LTR until more definitive predictors of these complications are identified.

Abstract Background Although many probiotic products are currently available in yogurt or pill form in the United States ( US ), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population. Objective This study examined how patients with chronic gastrointestinal ( GI ) diseases view the regulation of probiotics. Design We conducted a multi‐site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review]. Results We conducted 22 focus groups with 136 patients with major gastrointestinal ( GI ) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs. Discussion and conclusion If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.

Sortilin 1 regulates the levels of brain progranulin (PGRN), a neurotrophic growth factor that, when deficient, is linked to cases of frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43)–positive inclusions (FTLD-TDP). We identified a specific splicing enhancer element that regulates the inclusion of a sortilin exon cassette (termed Ex17b) not normally present in the mature sortilin mRNA. This enhancer element is consistently present in sortilin RNA of mice and other species but absent in primates, which carry a premature stop codon within the Ex17b sequence. In the absence of TDP-43, which acts as a regulatory inhibitor, Ex17b is included in the sortilin mRNA. In humans, in contrast to mice, the inclusion of Ex17b in sortilin mRNA generates a truncated, nonfunctional, extracellularly released protein that binds to but does not internalize PGRN, essentially acting as a decoy receptor. Based on these results, we propose a potential mechanism linking misregulation of sortilin splicing with altered PGRN metabolism.

AbstractEmphasis on translational research to facilitate progression from the laboratory into the community also creates a dynamic in which ethics and social policy questions and solutions are ever pressing. In response, academic institutions are creating Research Ethics Consultation Services (RECS). All Clinical Translational Science Award institutions were surveyed in early 2010 to determine which institutions have a RECS in operation and what is their composition and function. Of the 46 institutions surveyed, 33 (70%) have a RECS. Only 15 RECS have received any consult requests in the last year. Issues that are common among these relatively nascent services include relationships with institutional oversight committees, balancing requestor concerns about confidentiality with research integrity and human subjects protection priorities, tracking consult data and outcomes, and developing systems for internal evaluation. There is variability in how these issues are approached. It will be important to be attentive to the institutional context to develop an appropriate approach. Further data about the issues raised by requestors and the recommendations provided are necessary to build a community of scholars who can navigate and resolve ethical issues encountered along the translational research pathway. Clin Trans Sci 2013; Volume 6: 40–44

Improving professional attitudes and behaviors requires critical self reflection. Research on reflection is necessary to understand professionalism among medical students. The aims of this prospective validation study at the Mayo Medical School and Cleveland Clinic Lerner College of Medicine were: (1) to develop and validate a new instrument for measuring reflection on professionalism, and (2) determine whether learner variables are associated with reflection on the gross anatomy experience. An instrument for assessing reflections on gross anatomy, which was comprised of 12 items structured on five‐point scales, was developed. Factor analysis revealed a three‐dimensional model including low reflection (four items), moderate reflection (five items), and high reflection (three items). Item mean scores ranged from 3.05 to 4.50. The overall mean for all 12 items was 3.91 (SD = 0.52). Internal consistency reliability (Cronbach's α) was satisfactory for individual factors and overall (Factor 1 α = 0.78; Factor 2 α = 0.69; Factor 3 α = 0.70; Overall α = 0.75). Simple linear regression analysis indicated that reflection scores were negatively associated with teamwork peer scores ( P = 0.018). The authors report the first validated measurement of medical student reflection on professionalism in gross anatomy. Critical reflection is a recognized component of professionalism and may be important for behavior change. This instrument may be used in future research on professionalism among medical students. Anat Sci Educ 6: 232–238. © 2012 American Association of Anatomists.