Lane Medical Library

Modeling Small Noncanonical RNA Motifs with the Rosetta FARFAR Server.

Methods Mol Biol. 2016;1490:187-198

Authors: Yesselman JD, Das R

Abstract
Noncanonical RNA motifs help define the vast complexity of RNA structure and function, and in many cases, these loops and junctions are on the order of only ten nucleotides in size. Unfortunately, despite their small size, there is no reliable method to determine the ensemble of lowest energy structures of junctions and loops at atomic accuracy. This chapter outlines straightforward protocols using a webserver for Rosetta Fragment Assembly of RNA with Full Atom Refinement (FARFAR) ( http://rosie.rosettacommons.org/rna_denovo/submit ) to model the 3D structure of small noncanonical RNA motifs for use in visualizing motifs and for further refinement or filtering with experimental data such as NMR chemical shifts.

PMID: 27665600 [PubMed - as supplied by publisher]

Equivalent survival after nipple-sparing compared to non-nipple-sparing mastectomy: data from California, 1988-2013.

Breast Cancer Res Treat. 2016 Sep 24;

Authors: Kurian AW, Canchola AJ, Gomez SL, Clarke CA

Abstract
PURPOSE: Nipple-sparing mastectomy, which may improve cosmesis, body image, and sexual function in comparison to non-nipple-sparing mastectomy, is increasingly used to treat early-stage breast cancer; however, long-term survival data are lacking. We evaluated survival after nipple-sparing mastectomy versus non-nipple-sparing mastectomy in a population-based cancer registry.
METHODS: We conducted an observational study using the California Cancer Registry, considering all stage 0-III breast cancers diagnosed in California from 1988 to 2013. We compared breast cancer-specific and overall survival time after nipple-sparing versus non-nipple-sparing mastectomy, using multivariable analysis.
RESULTS: Among 157,592 stage 0-III female breast cancer patients treated with unilateral mastectomy from 1988-2013, 993 (0.6 %) were reported as having nipple-sparing and 156,599 (99.4 %) non-nipple-sparing mastectomies; median follow-up was 7.9 years. The proportion of mastectomies that were nipple-sparing increased over time (1988, 0.2 %; 2013, 5.1 %) and with neighborhood socioeconomic status, and decreased with age and stage. On multivariable analysis, nipple-sparing mastectomy was associated with a lower risk of breast cancer-specific mortality compared to non-nipple-sparing mastectomy [hazard ratio (HR) 0.71, 95 % confidence interval (CI) 0.51-0.98]. However, when restricting to diagnoses 1996 or later and adjusting for a larger set of covariates, risk was attenuated (HR 0.86, 95 % CI 0.52-1.42).
CONCLUSIONS: Among California breast cancer patients diagnosed from 1988-2013, nipple-sparing mastectomy was not associated with worse survival than non-nipple-sparing mastectomy. These results may inform the decisions of patients and doctors deliberating between these surgical approaches for breast cancer treatment.

PMID: 27665587 [PubMed - as supplied by publisher]

Healthcare worker and family caregiver hand hygiene in Bangladeshi healthcare facilities: results from the Bangladesh National Hygiene Baseline Survey.

J Hosp Infect. 2016 Aug 24;

Authors: Horng LM, Unicomb L, Alam MU, Halder AK, Shoab AK, Ghosh PK, Opel A, Islam MK, Luby SP

Abstract
BACKGROUND: Healthcare facility hand hygiene impacts patient care, healthcare worker safety, and infection control, but low-income countries have few data to guide interventions.
AIM: To conduct a nationally representative survey of hand hygiene infrastructure and behaviour in Bangladeshi healthcare facilities to establish baseline data to aid policy.
METHODS: The 2013 Bangladesh National Hygiene Baseline Survey examined water, sanitation, and hand hygiene across households, schools, restaurants and food vendors, traditional birth attendants, and healthcare facilities. We used probability proportional to size sampling to select 100 rural and urban population clusters, and then surveyed hand hygiene infrastructure in 875 inpatient healthcare facilities, observing behaviour in 100 facilities.
FINDINGS: More than 96% of facilities had 'improved' water sources, but environmental contamination occurred frequently around water sources. Soap was available at 78-92% of handwashing locations for doctors and nurses, but just 4-30% for patients and family. Only 2% of 4676 hand hygiene opportunities resulted in recommended actions: using alcohol sanitizer or washing both hands with soap, then drying by air or clean cloth. Healthcare workers performed recommended hand hygiene in 9% of 919 opportunities: more after patient contact (26%) than before (11%). Family caregivers frequently washed hands with only water (48% of 2751 opportunities), but with little soap (3%).
CONCLUSION: Healthcare workers had more access to hand hygiene materials and performed better hand hygiene than family, but still had low adherence. Increasing hand hygiene materials and behaviour could improve infection control in Bangladeshi healthcare facilities.

PMID: 27665311 [PubMed - as supplied by publisher]

Nutritional interventions in primary mitochondrial disorders: Developing an evidence base.

Mol Genet Metab. 2016 Sep 20;

Authors: Camp KM, Krotoski D, Parisi MA, Gwinn KA, Cohen BH, Cox CS, Enns GM, Falk MJ, Goldstein AC, Gopal-Srivastava R, Gorman GS, Hersh SP, Hirano M, Hoffman FA, Karaa A, MacLeod EL, McFarland R, Mohan C, Mulberg AE, Odenkirchen JC, Parikh S, Rutherford PJ, Suggs-Anderson SK, Tang WH, Vockley J, Wolfe LA, Yannicelli S, Yeske PE, Coates PM

Abstract
In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD.

PMID: 27665271 [PubMed - as supplied by publisher]

Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study).

Am J Cardiol. 2016 Aug 12;

Authors: Schopfer DW, Regan M, Heidenreich PA, Whooley MA

Abstract
Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly influenced by depressive symptoms as it is by cardiovascular disease severity.

PMID: 27665203 [PubMed - as supplied by publisher]

Impact of Longitudinal Lesion Geometry on Location of Plaque Rupture and Clinical Presentations.

JACC Cardiovasc Imaging. 2016 Sep 16;

Authors: Lee JM, Choi G, Hwang D, Park J, Kim HJ, Doh JH, Nam CW, Na SH, Shin ES, Taylor CA, Koo BK

Abstract
OBJECTIVES: This study sought to investigate the impact of longitudinal lesion geometry on the location of plaque rupture and clinical presentation and its mechanism.
BACKGROUND: The relationships among lesion geometry, external hemodynamic forces acting on the plaque, location of plaque rupture, and clinical presentation have not been comprehensively investigated.
METHODS: This study enrolled 125 patients with plaque rupture documented by intravascular ultrasound. Longitudinal locations of plaque rupture were identified and categorized by intravascular ultrasound. Patients' clinical presentations and TIMI (Thrombolysis in Myocardial Infarction) flow grade in an initial angiogram were compared according to the location of plaque rupture. Longitudinal lesion asymmetry was quantitatively assessed by the luminal radius change over the segment length (radius gradient [RG]). Lesions with a steeper radius change in the upstream segment compared with the downstream segment (RGupstream > RGdownstream) were defined as upstream-dominant lesions.
RESULTS: On the basis of the site of maximum rupture aperture, 56.0%, 16.0%, and 28.0% of the patients had upstream, minimal lumen area, and downstream rupture, respectively. Patients with upstream rupture more frequently presented with ST-segment elevation myocardial infarction (45.7%, 40.0%, 22.9%; p = 0.030) and with TIMI flow grade <3 (32.9%, 20.0%, 17.1%; p = 0.042). According to the ratio of upstream and downstream RG, 69.5% of lesions were classified as upstream-dominant lesions, and 30.5% were classified as downstream-dominant lesions. Among the 66 upstream-dominant lesions, 65 cases (98.5%) had upstream rupture, and the RG ratio (RGupstream/RGdownstream) was an independent predictor of upstream rupture (odds ratio: 1.481; 95% confidence interval: 1.035 to 2.120; p = 0.032). Upstream-dominant lesions more frequently manifested with ST-segment elevation myocardial infarction than did downstream-dominant lesions (48.5% vs. 24.1%; p = 0.026).
CONCLUSIONS: Both clinical presentation and degree of flow limitation were associated with the location of plaque rupture. Longitudinal lesion asymmetry assessed by RG, which can affect regional distribution of hemodynamic stress, was associated with the location of rupture and with clinical presentation.

PMID: 27665158 [PubMed - as supplied by publisher]