WII-FIT FOR BALANCE AND GAIT IN SKILLED NURSING FACILITY: A RETROSPECTIVE STUDY

Background: Falls in elderly are a major public health problem. Poor balance and gait abnormalities are risk factors for falls. Exercise improves gait and balance in elderly. However, it is difficult to engage patients in exercise programs. Wii-Fit might bridge this gap by providing high level of engagement at an affordable price. Wii-Fit is a Nintendo game used for balance, yoga, aerobics, and strength training. It is a TV based self-directed activity. Virtual trainers talk the user through the activity and track progress while visual and auditory feedback improve engagement. Anecdotal reports suggest improvement in balance and social benefits with Wii-Fit, but no systematic studies are available. Objective: To compare the effect of Wii-Fit augmentation to physical therapy alone in subjects undergoing rehabilitation in skilled nursing facility (SNF) using a retrospective chart review. Methods: 100 charts were reviewed of which seventeen patients were noted to have used Wii-Fit during their rehabilitation. These subjects were matched with seventeen controls who did physical therapy alone. Results: There were no baseline differences between the groups. The mean age was 77.7 years, with 11 females in each group. All the subjects were Caucasians. The average length of stay was 30 days in each group. Mean duration of the Wii-Fit use was 4-weeks. Wii-Fit augmentation group improved significantly in Activities of Daily Living (p=0.008), balance (p=0.0001), and assistance with gait (p=0.05) when compared to the control group. Conclusion: Wii-Fit can be used safely in a SNF, and it may improve balance, gait, and functional status

Resolving the contributions of the membrane-bound and periplasmic nitrate reductase systems to nitric oxide and nitrous oxide production in Salmonella enterica serovar Typhimurium

The production of cytotoxic nitric oxide (NO) and conversion into the neuropharmacological agent and potent greenhouse gas nitrous oxide (N2O) is linked with anoxic nitrate catabolism by Salmonella enterica serovar Typhimurium. Salmonella can synthesize two types of nitrate reductase: a membrane-bound form (Nar) and a periplasmic form (Nap). Nitrate catabolism was studied under nitrate-rich and nitrate-limited conditions in chemostat cultures following transition from oxic to anoxic conditions. Intracellular NO production was reported qualitatively by assessing transcription of the NO-regulated genes encoding flavohaemoglobin (Hmp), flavorubredoxin (NorV) and hybrid cluster protein (Hcp). A more quantitative analysis of the extent of NO formation was gained by measuring production of N2O, the end-product of anoxic NO-detoxification. Under nitrate-rich conditions, the nar, nap, hmp, norV and hcp genes were all induced following transition from the oxic to anoxic state, and 20% of nitrate consumed in steady-state was released as N2O when nitrite had accumulated to millimolar levels. The kinetics of nitrate consumption, nitrite accumulation and N2O production were similar to those of wild-type in nitrate-sufficient cultures of a nap mutant. In contrast, in a narG mutant, the steady-state rate of N2O production was ~30-fold lower than that of the wild-type. Under nitrate-limited conditions, nap, but not nar, was up-regulated following transition from oxic to anoxic metabolism and very little N2O production was observed. Thus a combination of nitrate-sufficiency, nitrite accumulation and an active Nar-type nitrate reductase leads to NO and thence N2O production, and this can account for up to 20% of the nitrate catabolized

Identification of outcomes to inform the development of a core outcome set for surgical innovation:a targeted review of case studies of novel surgical devices

OBJECTIVE: Outcome selection and reporting in studies of novel surgical procedures and devices lacks standardisation, hindering safe and effective evaluation. A core outcome set (COS) to measure and report in all studies of surgical innovation is needed. We explored outcomes in a specific sample of innovative surgical device case studies to identify outcome domains specifically relevant to innovation to inform the development of a COS. DESIGN: A targeted review of 11 purposive selected case studies of innovative surgical devices. METHODS: Electronic database searches in PubMed (July 2018) identified publications reporting the introduction and evaluation of each device. Outcomes were extracted and categorised into domains until no new domains were conceptualised. Outcomes specifically relevant to evaluating innovation were further scrutinised. RESULTS: 112 relevant publications were identified, and 5926 outcomes extracted. Heterogeneity in study type, outcome selection and reporting was observed across surgical devices. Categorisation of outcomes was performed for 2689 (45.4%) outcomes into five broad outcome domains. Outcomes considered key to the evaluation of innovation (n=66; 2.5%) were further categorised as surgeon/operator experience (n=40; 1.5%), unanticipated events (n=15, 0.6%) and modifications (n=11; 0.4%). CONCLUSION: Outcome domains unique to evaluating innovative surgical devices have been identified. Findings have been combined with multiple other data sources relevant to the evaluation of surgical innovation to inform the development of a COS to measure and report in all studies evaluating novel surgical procedures/devices

In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial.

BACKGROUND: The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population. METHODS: This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy. Participants in UKALL14 had B-cell or T-cell acute lymphoblastic leukaemia, were aged 25-65 years (BCR-ABL1-negative) or 18-65 years (BCR-ABL1-positive), and for this subcohort had a fit, matched sibling donor or an 8 out of 8 allelic matched unrelated donor (HLA-A, HLA-B, HLA-C, and HLA-DR). On June 20, 2014, the protocol was amended to allow 7 out of 8 matched unrelated donors if the patient had high risk cytogenetics or was minimal residual disease (MRD)-positive after the second induction course. Patients were given fludarabine, melphalan, and alemtuzumab (FMA; intravenous fludarabine 30 mg/m2 on days -6 to -2, melphalan 140 mg/m2 on day -2, and alemtuzumab 30 mg on day -1 [sibling donor] and days -2 and -1 [unrelated donor]) before allogeneic HSCT (aged ≥41 years patient pathway). Donor lymphocyte infusions were given from 6 months for mixed chimerism or MRD. The primary endpoint was event-free survival and secondary and transplantation-specific endpoints included overall survival, relapse incidence, TRM, and acute and chronic graft-versus-host disease (GVHD). This study is registered with ClinicalTrials.gov, NCT01085617. FINDINGS: From Feb 22, 2011, to July 26, 2018, 249 patients (236 aged ≥41 years and 13 younger than 41 years) considered unfit for a myeloablative allograft received an FMA reduced-intensity conditioned HSCT. 138 (55%) patients were male and 111 (45%) were female. 88 (35%) participants received transplantations from a sibling donor and 160 (64%) received transplantations from unrelated donors. 211 (85%) participants had B-precursor acute lymphoblastic leukaemia. High-risk cytogenetics were present in 43 (22%) and another 63 (25%) participants were BCR-ABL1-positive. At median follow-up of 49 months (IQR 36-70), 4-year event-free survival was 46·8% (95% CI 40·1-53·2) and 4-year overall survival was 54·8% (48·0-61·2). 4-year cumulative incidence of relapse was 33·6% (27·9-40·2) and 4-year TRM was 19·6% (15·1-25·3). 27 (56%) of 48 patients with TRM had infection as the named cause of death. Seven (15%) of 48 patients had fungal infections, 13 (27%) patients had bacterial infections (six gram-negative), and 11 (23%) had viral infections (three cytomegalovirus and two Epstein-Barr virus). Acute GVHD grade 2-4 occurred in 29 (12%) of 247 patients and grade 3-4 occurred in 12 (5%) patients. Chronic GVHD incidence was 84 (37%) of 228 patients (50 [22%] had extensive chronic GVHD). 49 (30%) of 162 patients had detectable end-of-induction MRD, which portended worse outcomes with event-free survival (HR 2·40 [95% CI 1·46-3·93]) and time-to-relapse (HR 2·41 [1·29-4·48]). INTERPRETATION: FMA reduced-intensity conditioned allogeneic HSCT in older patients with acute lymphoblastic leukaemia in first complete remission provided good disease control with moderate GVHD, resulting in better-than-expected event-free survival and overall survival in this high-risk population. Strategies to reduce infection-related TRM will further improve outcomes. FUNDING: Cancer Research UK

Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment

Background Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. Results A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28°C) and human (37°C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. Conclusions We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of EPS properties. Despite its abundance and conservation in the genus, we find no evidence for a role of Pam in either virulence or symbiosis

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

<p>Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.</p> <p>Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.</p> <p>Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.</p&gt

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve