Can balance function tests predict disability in older adults with peripheral vestibular hypofunction?

Introduction: The Dizziness Handicap Inventory (DHI) is a 25-item self-assessment questionnaire used to evaluate perceived disability from dizziness. The predictive validity of Timed Up and Go (TUG), Dynamic Gait Index (DGI), and modified Clinical Test of Sensory Integration of Balance (mCTSIB) on disability as shown by DHI has not been established specific to older adults with peripheral vestibular hypofunction. The purpose of this study is to investigate if the TUG, DGI, and mCTSIB are significant and strong predictors of the disability from dizziness as represented by the DHI scores in older adults with peripheral vestibular hypofunction. Methods: A Correlational, Retrospective Design was used to investigate the predictors of the DHI score. Data was collected retrospectively on the 17 patients in the main study ‘The Impact of Prescribed Walking on Dizziness in Seniors with Vestibular Hypofunction: A Pilot Randomized Controlled Trial’ and from physical therapy medical charts (n=24) from June 2015 to June 2018. Only medical charts of those 65 years and older who underwent vestibular physical therapy and contain all four outcome measures (DHI, DGI, mCTSIB, and TUG) were included in the study. Dizziness related to central nervous disorder were excluded. Results: There was a significant fair inverse correlation between DHI and mCTSIB (r = -0.381, p = 0.01) and DGI (r = -0.322, p = 0.01), and a fair correlation with TUG (r = 0.396, p = 0.03). The mCTSIB, TUG, and DGI accounted for 10% of the variance in the DHI, however, this predictive relationship was not found to be significant. Discussion: In this limited sample size, the TUG, DGI, and mCTSIB tests are not significant and strong predictors of dizziness-related disability as represented by the DHI scores in older adults with peripheral vestibular dysfunction. This study should be replicated as a large-scale prospective study with stratification of severity of dizziness to improve the generalizability of findings

Maternal ethnobotanical knowledge is associated with multiple measures of child health in the Bolivian Amazon

Premi a l'excel·lència investigadora. Àmbit de les Ciències Socials. 2008Culture is a critical determinant of human behavior and health, and the intergenerational transmission of knowledge regarding the use of available plant resources has historically been an essential function of culture. Local ethnobotanical knowledge is important for health and nutrition, particularly in rural low-resource settings, but cultural and economic transitions associated with globalization threaten such knowledge. This prospective study investigates the association between parental ethnobotanical knowledge and child health among the Tsimane', a horticulturalist and foraging society in Amazonian Bolivia. Anthropometric data and capillary blood samples were collected from 330 Tsimane' 2- to 10-year-olds, and mothers and fathers were interviewed to assess ethnobotanical knowledge and skills. Comprehensive measures of parental schooling, acculturation, and economic activities were also collected. Dependent variables included three measures of child health: (i) C-reactive protein, assayed in whole-blood spots as an indicator of immunostimulation; (ii) skinfold thickness, to estimate subcutaneous fat stores necessary to fuel growth and immune function; and (iii) height-for-age, to assess growth stunting. Each child health measure was associated with maternal ethnobotanical knowledge, independent of a wide range of potentially confounding variables. Each standard deviation of maternal ethnobotanical knowledge increased the likelihood of good child health by a factor of >1.5. Like many populations around the world, the Tsimane' are increasingly facing the challenges and opportunities of globalization. These results underscore the importance of local cultural factors to child health and document a potential cost if ethnobotanical knowledge is lost

DJ-1 Mutations are Rare in a Swedish Parkinson Cohort

Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide

Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control

The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1, are associated with early-onset familial Parkinson’s disease and lead to pathological oxidative stress and/or disrupted protein degradation by the proteasome. The aim of this study was to gain insights into the pathogenic mechanisms of selected DJ-1 missense mutations, by characterizing protein–protein interactions, core parameters of mitochondrial function, quality control regulation via autophagy, and cellular death following dopamine accumulation. We report that the DJ-1M26I mutant influences DJ-1 interactions with SUMO-1, in turn enhancing removal of mitochondria and conferring increased cellular susceptibility to dopamine toxicity. By contrast, the DJ-1D149A mutant does not influence mitophagy, but instead impairs Ca2+ dynamics and free radical homeostasis by disrupting DJ-1 interactions with a mitochondrial accessory protein known as DJ-1-binding protein (DJBP/EFCAB6). Thus, individual DJ-1 mutations have different effects on mitochondrial function and quality control, implying mutation-specific pathomechanisms converging on impaired mitochondrial homeostasis

Physiotherapy versus placebo or no intervention in Parkinson's disease

Background: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well-being, thereby enhancing quality of life.  Objectives: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD.  Search methods: We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012.  Selection criteria: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD.  Data collection and analysis: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions.  Main results: We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson’s Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed.  Authors' conclusions: Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.  This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD

BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity

The L166P mutation in DJ-1 is associated with Parkinson’s disease. DJ-1–interacting protein BAG1 chaperones mutant DJ-1 and reverses its mutant phenotype

Pumilio directs deadenylation-associated translational repression of the cyclin-dependent kinase 1 activator RGC-32

Response gene to complement-32 (RGC-32) activates cyclin-dependent kinase 1, regulates the cell cycle and is deregulated in many human tumours. We previously showed that RGC-32 expression is upregulated by the cancer-associated Epstein-Barr virus (EBV) in latently infected B cells through the relief of translational repression. We now show that EBV infection of naïve primary B cells also induces RGC-32 protein translation. In EBV-immortalised cell lines, we found that RGC-32 depletion resulted in cell death, indicating a key role in B cell survival. Studying RGC-32 translational control in EBV-infected cells, we found that the RGC-32 3′untranslated region (3′UTR) mediates translational repression. Repression was dependent on a single Pumilio binding element (PBE) adjacent to the polyadenylation signal. Mutation of this PBE did not affect mRNA cleavage, but resulted in increased polyA tail length. Consistent with Pumilio-dependent recruitment of deadenylases, we found that depletion of Pumilio in EBV-infected cells increased RGC-32 protein expression and polyA tail length. The extent of Pumilio binding to the endogenous RGC-32 mRNA in EBV-infected cell lines also correlated with RGC-32 protein expression. Our data demonstrate the importance of RGC-32 for the survival of EBV-immortalised B cells and identify Pumilio as a key regulator of RGC-32 translation