Does cueing training improve physical activity in patients with Parkinson's disease?

Patients with Parkinson’s disease (PD) are encouraged to stay active to maintain their mobility. Ambulatory activity monitoring (AM) provides an objective way to determine type and amount of gait-related daily activities. Objective To investigate the effects of a home cueing training program on functional walking activity in PD. Methods In a single-blind, randomized crossover trial, PD patients allocated to early intervention received cueing training for 3 weeks, whereas the late intervention group received training in the following 3 weeks. Training was applied at home, using a prototype cueing device. AM was applied at baseline, 3, 6, and 12 weeks in the patient’s home, to record body movements. Postures and motions were classified as percentage of total time spent on (a) static activity, further specified as % sitting and % standing, and (b) % dynamic activity, further specified as % walking, % walking periods exceeding 5 seconds (W>5s) and 10 seconds (W>10s). Random coefficient analysis was applied. Results A total of 153 patients participated in this trial. Significant improvements were found for dynamic activity ( = 4.46; P 5s ( = 2.63; P 10s ( = 2.90; P < .01). All intervention effects declined significantly at 6 weeks follow-up. Conclusion Cueing training in PD patients’ own home significantly improves the amount of walking as recorded by AM. Treatment effects reduced after the intervention period, pointing to the need for permanent cueing devices and follow-up cueing training

Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA.

An essential mechanism for repairing DNA double-strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single-stranded DNA, promoting DNA-strand exchange. Here, we study the interaction of hRAD51 with single-stranded DNA using a single-molecule approach. We show that ATP-bound hRAD51 filaments can exist in two different states with different contour lengths and with a free-energy difference of ~4 kBT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly-competent ADP-bound configuration. In agreement with the single-molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51-ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51-ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange

An evaluation of the integration of non-traditional learning tools into a community based breast and cervical cancer education program: The witness project of Buffalo

BACKGROUND: Breast and cervical cancer continue to represent major health challenges for African American women. among Caucasian women. The underlying reasons for this disparity are multifactorial and include lack of education and awareness of screening and early detection. Traditional educational methods have enjoyed varied success in the African American community and spawned development of novel educational approaches. Community based education programs employing a variety of educational models have been introduced. Successful programs must train and provide lay community members with the tools necessary to deliver strong educational programs. METHODS: The Witness Project is a theory-based, breast and cervical cancer educational program, delivered by African American women, that stresses the importance of early detection and screening to improve survival and teaches women how to perform breast self examination. Implementing this program in the Buffalo Witness Project of Buffalo required several modifications in the curriculum, integration of non-traditional learning tools and focused training in clinical study participation. The educational approaches utilized included repetition, modeling, building comprehension, reinforcement, hands on learning, a social story on breast health for African American women, and role play conversations about breast and cervical health and support. RESULTS: Incorporating non-traditional educational approaches into the Witness Project training resulted in a 79% improvement in the number of women who mastered the didactic information. A seventy-two percent study participation rate was achieved by educating the community organizations that hosted Witness Project programs about the informed consent process and study participation. CONCLUSION: Incorporating non-traditional educational approaches into community outreach programs increases training success as well as community participation

The role of statins in prevention and treatment of community acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications. PURPOSE: Performed a systematic review to address the role of statins in the prevention or treatment of CAP. DATA SOURCE: Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies. STUDY SELECTION: Two authors independently reviewed studies that examined the role of statins in CAP. DATA EXTRACTION: Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted. DATA SYNTHESIS: Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder. CONCLUSIONS: Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias

Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex

Topoisomerase IIIα is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. TRR plays an essential role in resolving DNA replication and recombination intermediates, often alongside the helicase BLM. While the TRR catalytic cycle is known to involve a protein-mediated single-stranded (ss)DNA gate, the detailed mechanism is not fully understood. Here, we probe the catalytic steps of TRR using optical tweezers and fluorescence microscopy. We demonstrate that TRR forms an open gate in ssDNA of 8.5 ± 3.8 nm, and directly visualize binding of a second ssDNA or double-stranded (ds)DNA molecule to the open TRR-ssDNA gate, followed by catenation in each case. Strikingly, dsDNA binding increases the gate size (by ~16%), while BLM alters the mechanical flexibility of the gate. These findings reveal an unexpected plasticity of the TRR-ssDNA gate size and suggest that TRR-mediated transfer of dsDNA may be more relevant in vivo than previously believed

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Construction of the Sophia Observation withdrawal Symptoms-scale (SOS) for critically ill children

Objective: To construct a reliable and clinically practical instrument for monitoring opioids and benzodiazepine withdrawal symptoms in pediatric ICU patients. Design: Instrument development. Setting: Intensive care unit in an academic children's hospital. Patients and participants: 79 patients up to age 16 years on intravenous midazolam and/or opioids for ≥5 days. An expert panel of 85 physicians and nurses rated clinical relevance of withdrawal symptoms. Intervention: During drug weaning repeated observations were performed with a checklist of 24 withdrawal symptoms described in the literature. Measurements and results: For 76 children, 932 observations were obtained within 24 h after decrease and/or discontinuation of midazolam or opioids. Most frequent symptoms were tachypnea, agitation, motor disturbance, diarrhea, fever, anxiety, sleep disturbance and hypertension (14.6-29.6%). Multidimensional scaling (MDS) was performed to detect the underlying empirical structure of co-occurrences of symptoms. An expert panel judged clinical relevance of each withdrawal symptom on a four-point scale ranging from 'definitively so' to 'definitively not'. Agitation, an