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Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice

Fri, 07/14/2017 - 3:36pm

Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and a decrease in mature lysosomes. The few developed sperm had disrupted axonemes and some retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins failed to be incorporated into sperm tails of the mutant mice, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of IFT-B complex, and IFT140, a component of IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components.

Eating Behaviors: Prevalence, Psychiatric Comorbidity, and Associations With Body Mass Index Among Male and Female Iraq and Afghanistan Veterans

Fri, 07/14/2017 - 3:36pm

OBJECTIVE: There is a dearth of research examining eating behaviors, such as binge eating, among male and female veterans. The present study evaluated the prevalence of self-reported eating problems as well as associations with body mass index and psychiatric disorders among male and female Iraq and Afghanistan veterans.

METHODS: Participants were 298 male and 364 female veterans (M = 33.3 +/- 10.6 years old) from the Women Veterans Cohort Study, a study of male and female veterans enrolled for Veterans Affairs care in New England or Indiana. Veterans self-reported on emotion- and stress-related eating, eating disorder diagnoses, and disordered eating behaviors. Diagnoses of post-traumatic stress disorder, major depressive disorder, and alcohol abuse were obtained from administrative records.

RESULTS: Female veterans reported higher rates of eating problems than did their male counterparts. Women and men who engage in disordered eating had higher rates of post-traumatic stress disorder and major depressive disorder, and women who engage in disordered eating had greater rates of alcohol abuse than did female veterans without eating disordered behaviors.

CONCLUSIONS: Disordered eating may be a significant issue among Iraq and Afghanistan veterans, and veterans with eating problems are more likely to have comorbid mental health conditions that further increase their health risks.

Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative

Fri, 07/14/2017 - 3:35pm

OBJECTIVE: The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk. METHODS: Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes. RESULTS: In age-adjusted models, women with the shortest ( < 30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment. CONCLUSIONS: Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

Calcium plus vitamin D supplementation and height loss: findings from the Women's Health Initiative Calcium and Vitamin D clinical trial

Fri, 07/14/2017 - 3:35pm

OBJECTIVE: The aim of this study was to determine the associations between calcium + vitamin D supplementation (vs placebo) and height loss in 36,282 participants of the Women's Health Initiative Calcium and Vitamin D trial.

METHODS: Post hoc analysis of data from a double-blind randomized controlled trial of 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily (CaD) or placebo in postmenopausal women at 40 US clinical centers. Height was measured annually (mean follow-up 5.9 y) with a stadiometer.

RESULTS: Average height loss was 1.28 mm/y among participants assigned to CaD versus 1.26 mm/y for women assigned to placebo (P = 0.35). Effect modification of the CaD intervention was not observed by age, race/ethnicity, or baseline intake of calcium or vitamin D. Randomization to the CaD group did not reduce the risk of clinical height loss (loss of > /=1.5 inches [3.8 cm]: hazard ratio (95% CI) = 1.00 (0.81, 1.23). A strong association (P < 0.001) was observed between age group and height loss. When we censored follow-up data in participants who became nonadherent to study pills, the results were similar to those of our primary analysis.

CONCLUSIONS: Compared with placebo, the CaD supplement used in this trial did not prevent height loss in healthy postmenopausal women.

Recurrent Clostridium difficile infection among Medicare patients in nursing homes: A population-based cohort study

Fri, 07/14/2017 - 3:35pm

We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals. We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age > /=65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for > /=3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without. Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1-3) among those with and 0 (IQR 0-1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1-21.4) and Medicare reimbursements $12,043 (95% CI $11,469-$12,617) in the group with a recurrence.Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare.

The Veterans Choice Act: A Qualitative Examination of Rapid Policy Implementation in the Department of Veterans Affairs

Fri, 07/14/2017 - 3:35pm

BACKGROUND: Congress enacted the Veterans Access, Choice, and Accountability Act of 2014 [Veterans Choice Act (VCA)] to improve access to timely, high-quality health care for Veterans. Although Congress mandated that VCA must begin within 90 days of passage of the legislation, no guidelines were provided in the legislation to ensure that Veterans had access to an adequate number of community providers across different specialties of care or distinct geographic areas, including rural areas of the country.

OBJECTIVE: To examine VCA policy implementation across a sampling of Veterans Health Administration (VHA) Medical Centers.

RESEARCH DESIGN: We conducted a qualitative study of 43 VHA staff and providers by conducting in-person interviews at 5 VA medical centers in the West, South, and Midwest United States. Interview questions focused on perceptions and experiences with VCA and challenges related to implementation for VHA staff and providers.

RESULTS: We identified 3 major themes to guide description of choice implementation: (1) VCA implemented too rapidly with inadequate preparation; (2) community provider networks insufficiently developed; and (3) communication and scheduling problems with subcontractors may lead to further delays in care.

CONCLUSIONS: Our evaluation suggests that VCA was implemented far too rapidly, with little consideration given to the adequacy of community provider networks available to provide care to Veterans. Given the challenges we have highlighted in VCA implementation, it is imperative that the VHA continue to develop care coordination systems that will allow the Veterans to receive seamless care in the community.

Psychometric Development of the Research and Knowledge Scale

Fri, 07/14/2017 - 3:35pm

BACKGROUND: Many research participants are misinformed about research terms, procedures, and goals; however, no validated instruments exist to assess individual's comprehension of health-related research information. We propose research literacy as a concept that incorporates understanding about the purpose and nature of research.

OBJECTIVES: We developed the Research and Knowledge Scale (RaKS) to measure research literacy in a culturally, literacy-sensitive manner. We describe its development and psychometric properties.

RESEARCH DESIGN: Qualitative methods were used to assess perspectives of research participants and researchers. Literature and informed consent reviews were conducted to develop initial items. These data were used to develop initial domains and items of the RaKS, and expert panel reviews and cognitive pretesting were done to refine the scale. We conducted psychometric analyses to evaluate the scale.

SUBJECTS: The cross-sectional survey was administered to a purposive community-based sample (n=430) using a Web-based data collection system and paper.

MEASURES: We did classic theory testing on individual items and assessed test-retest reliability and Kuder-Richardson-20 for internal consistency. We conducted exploratory factor analysis and analysis of variance to assess differences in mean research literacy scores in sociodemographic subgroups. RESULTS: The RaKS is comprised of 16 items, with a Kuder-Richardson-20 estimate of 0.81 and test-retest reliability 0.84. There were differences in mean scale scores by race/ethnicity, age, education, income, and health literacy (all P < 0.01).

CONCLUSIONS: This study provides preliminary evidence for the reliability and validity of the RaKS. This scale can be used to measure research participants' understanding about health-related research processes and identify areas to improve informed decision-making about research participation.

Measuring Harm in Health Care: Optimizing Adverse Event Review

Fri, 07/14/2017 - 3:35pm

OBJECTIVE: The objective of this study was to identify modifiable factors that improve the reliability of ratings of severity of health care-associated harm in clinical practice improvement and research.

METHODS: A diverse group of clinicians rated 8 types of adverse events: blood product, device or medical/surgical supply, fall, health care-associated infection, medication, perinatal, pressure ulcer, surgery. We used a generalizability theory framework to estimate the impact of number of raters, rater experience, and rater provider type on reliability.

RESULTS: Pharmacists were slightly more precise and consistent in their ratings than either physicians or nurses. For example, to achieve high reliability of 0.83, 3 physicians could be replaced by 2 pharmacists without loss in precision of measurement. If only 1 rater was available for rating, approximately 5% of the reviews for severe harm would have been incorrectly categorized. Reliability was greatly improved with 2 reviewers.

CONCLUSIONS: We identified factors that influence the reliability of clinician reviews of health care-associated harm. Our novel use of generalizability analyses improved our understanding of how differences affect reliability. This approach was useful in optimizing resource utilization when selecting raters to assess harm and may have similar applications in other settings in health care.

Risk assessment matters, but only when implemented well: A multisite study in juvenile probation

Fri, 07/14/2017 - 3:35pm

There is a strong movement toward juvenile justice agencies' use of risk assessment and risk-need-responsivity approaches to improve case management decisions for young offenders. However, little is known about whether adoption of risk assessment actually effectuates any changes in the way young offenders are handled. This was a multisite study of the impact on case processing of implementation of the Structured Assessment of Violence Risk in Youth (SAVRY) or Youth Level of Service/Case Management Inventory in 6 juvenile probation offices using a prepost design and 1,694 propensity score-matched young offenders. Consistent with the risk principle, there were significant changes to at least some areas of case processing in all but 1 site, most notably with respect to decreases in the amount of supervision youth received and in rates of out-of-home placement. The nature and extent of the impact varied as a function of sites' characteristics and implementation quality, not as a function of the risk assessment used. No increases in recidivism were observed in any site, and there was a significant reduction in recidivism in 1 site. The key benefits of implementation of valid risk assessment and case management procedures were improved resource allocation and fewer instances of inappropriate interference in youths' lives without an apparent increased risk to public safety.

Virtual Patient Technology: Engaging Primary Care in Quality Improvement Innovations

Fri, 07/14/2017 - 3:35pm

BACKGROUND: Engaging health care staff in new quality improvement programs is challenging.

OBJECTIVE: We developed 2 virtual patient (VP) avatars in the context of a clinic-level quality improvement program. We sought to determine differences in preferences for VPs and the perceived influence of interacting with the VP on clinical staff engagement with the quality improvement program.

METHODS: Using a participatory design approach, we developed an older male smoker VP and a younger female smoker VP. The older male smoker was described as a patient with cardiovascular disease and was ethnically ambiguous. The female patient was younger and was worried about the impact of smoking on her pregnancy. Clinical staff were allowed to choose the VP they preferred, and the more they engaged with the VP, the more likely the VP was to quit smoking and become healthier. We deployed the VP within the context of a quality improvement program designed to encourage clinical staff to refer their patients who smoke to a patient-centered Web-assisted tobacco intervention. To evaluate the VPs, we used quantitative analyses using multivariate models of provider and practice characteristics and VP characteristic preference and analyses of a brief survey of positive deviants (clinical staff in practices with high rates of encouraging patients to use the quit smoking innovation).

RESULTS: A total of 146 clinical staff from 76 primary care practices interacted with the VPs. Clinic staff included medical providers (35/146, 24.0%), nurse professionals (19/146, 13.0%), primary care technicians (5/146, 3.4%), managerial staff (67/146, 45.9%), and receptionists (20/146, 13.7%). Medical staff were mostly male, and other roles were mostly female. Medical providers (OR 0.031; CI 0.003-0.281; P=.002) and younger staff (OR 0.411; CI 0.177-0.952; P=.038) were less likely to choose the younger, female VP when controlling for all other characteristics. VP preference did not influence online patient referrals by staff. In high-performing practices that referred 20 or more smokers to the ePortal (13/76), the majority of clinic staff were motivated by or liked the virtual patient (20/26, 77%).

CONCLUSIONS: Medical providers are more likely motivated by VPs that are similar to their patient population, while nurses and other staff may prefer avatars that are more similar to them.

Peter Hotez, MD, PhD at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:41pm

Keynote speaker, Peter Hotez, MD, PhD, at the 7th annual UMCCTS Research Retreat held Tuesday, May 16, 2017 at UMass Medical School, Worcester, MA.

Peter Hotez, MD, PhD, and Katherine Luzuriaga, MD, at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:41pm

Keynote speaker, Peter Hotez, MD, PhD and Katherine Luzuriaga, MD, at the 7th annual UMCCTs Research Retreat held Tuesday, May 16, 2017 at UMass Medical School, Worcester, MA.

Attendees at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

Attendees at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

Attendees at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

3D Printing Exhibit at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

Poster Session at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

Poster Session at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.

Poster Session at 2017 UMCCTS Research Retreat

Tue, 07/11/2017 - 1:40pm

7th annual UMass Center for Clinical and Translational Science Research Retreat held Tuesday, May 16, 2017 at UMass Medical School,Worcester, MA.