A custom-built step exergame training programme to prevent falls in people with multiple sclerosis: A multicentre randomised controlled trial.

BACKGROUND: Cognitive-motor step training can improve stepping, balance and mobility in people with multiple sclerosis (MS), but effectiveness in preventing falls has not been demonstrated. OBJECTIVES: This multisite randomised controlled trial aimed to determine whether 6 months of home-based step exergame training could reduce falls and improve associated risk factors compared with usual care in people with MS. METHODS: In total, 461 people with MS aged 22-81 years were randomly allocated to usual care (control) or unsupervised home-based step exergame training (120 minutes/week) for 6 months. The primary outcome was rate of falls over 6 months from randomisation. Secondary outcomes included physical, cognitive and psychosocial function at 6 months and falls over 12 months. RESULTS: Mean (standard deviation (SD)) weekly training duration was 70 (51) minutes over 6 months. Fall rates did not differ between intervention and control groups (incidence rates (95% confidence interval (CI)): 2.13 (1.57-2.69) versus 2.24 (1.35-3.13), respectively, incidence rate ratio: 0.96 (95% CI: 0.69-1.34, p = 0.816)). Intervention participants performed faster in tests of choice-stepping reaction time at 6 months. No serious training-related adverse events were reported. CONCLUSION: The step exergame training programme did not reduce falls among people with MS. However, it significantly improved choice-stepping reaction time which is critical to ambulate safely in daily life environment.

Reducing the burden of dizziness in middle-aged and older people: A multifactorial, tailored, single-blind randomized controlled trial.

BACKGROUND: Dizziness is common among older people and is associated with a cascade of debilitating symptoms, such as reduced quality of life, depression, and falls. The multifactorial aetiology of dizziness is a major barrier to establishing a clear diagnosis and offering effective therapeutic interventions. Only a few multidisciplinary interventions of dizziness have been conducted to date, all of a pilot nature and none tailoring the intervention to the specific causes of dizziness. Here, we aimed to test the hypothesis that a multidisciplinary dizziness assessment followed by a tailored multifaceted intervention would reduce dizziness handicap and self-reported dizziness as well as enhance balance and gait in people aged 50 years and over with dizziness symptoms. METHODS AND FINDINGS: We conducted a 6-month, single-blind, parallel-group randomized controlled trial in community-living people aged 50 years and over who reported dizziness in the past year. We excluded individuals currently receiving treatment for their dizziness, those with degenerative neurological conditions including cognitive impairment, those unable to walk 20 meters, and those identified at baseline assessment with conditions that required urgent treatment. Our team of geriatrician, vestibular neuroscientist, psychologist, exercise physiologist, study coordinator, and baseline assessor held case conferences fortnightly to discuss and recommend appropriate therapy (or therapies) for each participant, based on their multidisciplinary baseline assessments. A total of 305 men and women aged 50 to 92 years (mean [SD] age: 67.8 [8.3] years; 62% women) were randomly assigned to either usual care (control; n = 151) or to a tailored, multifaceted intervention (n = 154) comprising one or more of the following: a physiotherapist-led vestibular rehabilitation programme (35% [n = 54]), an 8-week internet-based cognitive-behavioural therapy (CBT) (19% [n = 29]), a 6-month Otago home-based exercise programme (24% [n = 37]), and/or medical management (40% [n = 62]). We were unable to identify a cause of dizziness in 71 participants (23% of total sample). Primary outcome measures comprised dizziness burden measured with the Dizziness Handicap Inventory (DHI) score, frequency of dizziness episodes recorded with monthly calendars over the 6-month follow-up, choice-stepping reaction time (CSRT), and gait variability. Data from 274 participants (90%; 137 per group) were included in the intention-to-treat analysis. At trial completion, the DHI scores in the intervention group (pre and post mean [SD]: 25.9 [19.2] and 20.4 [17.7], respectively) were significantly reduced compared with the control group (pre and post mean [SD]: 23.0 [15.8] and 21.8 [16.4]), when controlling for baseline scores (mean [95% CI] difference between groups [baseline adjusted]: -3.7 [-6.2 to -1.2]; p = 0.003). There were no significant between-group differences in dizziness episodes (relative risk [RR] [95% CI]: 0.87 [0.65 to 1.17]; p = 0.360), CSRT performance (mean [95% CI] difference between groups [baseline adjusted]: -15 [-40 to 10]; p = 0.246), and step-time variability during gait (mean [95% CI] difference between groups [baseline adjusted]: -0.001 [-0.002 to 0.001]; p = 0.497). No serious intervention-related adverse events occurred. Study limitations included the low initial dizziness severity of the participants and the only fair uptake of the falls clinic (medical management) and the CBT interventions. CONCLUSIONS: A multifactorial tailored approach for treating dizziness was effective in reducing dizziness handicap in community-living people aged 50 years and older. No difference was seen on the other primary outcomes. Our findings therefore support the implementation of individualized, multifaceted evidence-based therapies to reduce self-perceived disability associated with dizziness in middle-aged and older people. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000379819.

A multidisciplinary intervention to prevent subsequent falls and health service use following fall-related paramedic care: a randomised controlled trial.

Background: approximately 25% of older people who fall and receive paramedic care are not subsequently transported to an emergency department (ED). These people are at high risk of future falls, unplanned healthcare use and poor health outcomes. Objective: to evaluate the impact of a fall-risk assessment and tailored fall prevention interventions among older community-dwellers not transported to ED following a fall on subsequent falls and health service use. Design, setting, participants: Randomised controlled trial involving 221 non-transported older fallers from Sydney, Australia. Intervention: the intervention targeted identified risk factors and used existing services to implement physiotherapy, occupational therapy, geriatric assessment, optometry and medication management interventions as appropriate. The control group received individualised written fall prevention advice. Measurements: primary outcome measures were rates of falls and injurious falls. Secondary outcome measures were ambulance re-attendance, ED presentation, hospitalisation and quality of life over 12 months. Analysis was by intention-to-treat and per-protocol according to self-reported adherence using negative binominal regression and multivariate analysis. Results: ITT analysis showed no significant difference between groups in subsequent falls, injurious falls and health service use. The per-protocol analyses revealed that the intervention participants who adhered to the recommended interventions had significantly lower rates of falls compared to non-adherers (IRR: 0.53 (95% CI : 0.32-0.87)). Conclusion: a multidisciplinary intervention did not prevent falls in older people who received paramedic care but were not transported to ED. However the intervention was effective in those who adhered to the recommendations. Trial registration: the trial is registered at the Australian New Zealand Clinical Trials Registry: ACTRN 12611000503921, 13/05/2011.

Tailored multifactorial intervention to improve dizziness symptoms and quality of life, balance and gait in dizziness sufferers aged over 50 years: protocol for a randomised controlled trial.

BACKGROUND: Dizziness is a frequently reported symptom in older people that can markedly impair quality of life. This manuscript presents the protocol for a randomised controlled trial, which has the main objective of determining the impact of comprehensive assessment followed by a tailored multifaceted intervention in reducing dizziness episodes and symptoms, improving associated impairments to balance and gait and enhancing quality of life in older people with self-reported significant dizziness. METHODS: Three hundred people aged 50 years or older, reporting significant dizziness in the past year will be recruited to participate in the trial. Participants allocated to the intervention group will receive a tailored, multifaceted intervention aimed at treating their dizziness symptoms over a 6 month trial period. Control participants will receive usual care. The primary outcome measures will be the frequency and duration of dizziness episodes, dizziness symptoms assessed with the Dizziness Handicap Inventory, choice-stepping reaction time and step time variability. Secondary outcomes will include health-related quality of life measures, depression and anxiety symptoms, concern about falling, balance and risk of falls assessed with the physiological fall risk assessment. Analyses will be by intention-to-treat. DISCUSSION: The study will determine the effectiveness of comprehensive assessment, combined with a tailored, multifaceted intervention on dizziness episodes and symptoms, balance and gait control and quality of life in older people experiencing dizziness. Clinical implications will be evident for the older population for the diagnosis and treatment of dizziness. TRIAL REGISTRATION: The study is registered with the Australia New Zealand Clinical Trials Registry ACTRN12612000379819 .

Ecotoxicological effects of carbon nanotubes and cellulose nanofibers in Chlorella vulgaris.

BACKGROUND: MWCNT and CNF are interesting NPs that possess great potential for applications in various fields such as water treatment, reinforcement materials and medical devices. However, the rapid dissemination of NPs can impact the environment and in the human health. Thus, the aim of this study was to evaluate the MWCNT and cotton CNF toxicological effects on freshwater green microalgae Chlorella vulgaris. RESULTS: Exposure to MWCNT and cotton CNF led to reductions on algal growth and cell viability. NP exposure induced reactive oxygen species (ROS) production and a decreased of intracellular ATP levels. Addition of NPs further induced ultrastructural cell damage. MWCNTs penetrate the cell membrane and individual MWCNTs are seen in the cytoplasm while no evidence of cotton CNFs was found inside the cells. Cellular uptake of MWCNT was observed in algae cells cultured in BB medium, but cells cultured in Seine river water did not internalize MWCNTs. CONCLUSIONS: Under the conditions tested, such results confirmed that exposure to MWCNTs and to cotton CNFs affects cell viability and algal growth.

Exergame and cognitive training for preventing falls in community-dwelling older people: a randomized controlled trial.

Exergame training, in which video games are used to promote exercise, can be tailored to address cognitive and physical risk factors for falls and is a promising method for fall prevention in older people. Here, we performed a randomized clinical trial using the smart±step gaming system to examine the effectiveness of two home-based computer game interventions, seated cognitive training and step exergame training, for fall prevention in community-dwelling older people, as compared with a minimal-intervention control group. Participants aged 65 years or older (n = 769, 71% female) living independently in the community were randomized to one of three arms: (1) cognitive training using a computerized touchpad while seated, (2) exergame step training on a computerized mat or (3) control (provided with an education booklet on healthy ageing and fall prevention). The rate of falls reported monthly over 12 months-the primary outcome of the trial-was significantly reduced in the exergame training group compared with the control group (incidence rate ratio = 0.74, 95% confidence interval = 0.56-0.98), but was not statistically different between the cognitive training and control groups (incidence rate ratio = 0.86, 95% confidence interval = 0.65-1.12). No beneficial effects of the interventions were found for secondary outcomes of physical and cognitive function, and no serious intervention-related adverse events were reported. The results of this trial support the use of exergame step training for preventing falls in community-dwelling older people. As this intervention can be conducted at home and requires only minimal equipment, it has the potential for scalability as a public health intervention to address the increasing problem of falls and fall-related injuries. Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616001325493 .

Identifying Key Risk Factors for Dizziness Handicap in Middle-Aged and Older People.

OBJECTIVES: More than 10% of people aged 50 years and older report dizziness. Despite available treatments, dizziness remains unresolved for many people due in part to suboptimal assessment. We aimed to identify factors associated with dizziness handicap in middle-aged and older people to identify targets for intervention to address this debilitating problem. A secondary aim was to determine whether factors associated with dizziness differed between middle-aged (<70 years) and older people (≥ 70 years). DESIGN: Secondary analysis of baseline and prospective data from a randomized controlled trial. SETTING AND PARTICIPANTS: In total, 305 individuals aged 50 to 92 years reporting significant dizziness in the past year were recruited from the community. METHODS: Participants were classified as having either mild or no dizziness handicap (score <31) or moderate/severe dizziness handicap (score: 31‒100) based on the Dizziness Handicap Inventory. Participants completed health questionnaires and underwent assessments of psychological well-being, lying and standing blood pressure, vestibular function, strength, vision, proprioception, processing speed, balance, stepping, and gait. Participants reported dizziness episodes in monthly diaries for 6 months following baseline assessment. RESULTS: Dizziness Handicap Inventory scores ranged from 0 to 86 with 95 participants (31%) reporting moderate/severe dizziness handicap. Many vestibular, cardiovascular, psychological, balance-related, and medical/medications measures were significantly associated with dizziness handicap severity and dizziness episode frequency. Binary logistic regression identified a positive Dix Hallpike/head-roll test for benign paroxysmal positional vertigo [odds ratio (OR) 2.09, 95% confidence interval (CI) (1.11‒3.97)], cardiovascular medication use [OR 1.90, 95% CI (1.09‒3.32)], high postural sway when standing on the floor with eyes closed (sway path ≥160 mm) [OR 2.97, 95% CI (1.73‒5.10)], and anxiety (Generalized Anxiety Disorder Scale 7-item Scale score ≥8) [OR 3.08, 95% CI (1.36‒6.94)], as significant and independent predictors of moderate/severe dizziness handicap. Participants aged 70 years and over were significantly more likely to report cardiovascular conditions than those aged less than 70 years old. CONCLUSIONS AND IMPLICATIONS: Assessments of cardiovascular conditions and cardiovascular medication use, benign paroxysmal positional vertigo, anxiety, and postural sway identify middle-aged and older people with significant dizziness handicap. A multifactorial assessment including these factors may assist in tailoring evidence-based therapies to alleviate dizziness handicap in this group.

Understanding the Psychological Impact of COVID-19 Pandemic on Patients With Cancer, Their Caregivers, and Health Care Workers in Singapore.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact, and Singapore has seen 33,000 confirmed cases. Patients with cancer, their caregivers, and health care workers (HCWs) need to balance the challenges associated with COVID-19 while ensuring that cancer care is not compromised. This study aimed to evaluate the psychological effect of COVID-19 on these groups and the prevalence of burnout among HCWs. METHODS: A cross-sectional survey of patients, caregivers, and HCWs at the National Cancer Centre Singapore was performed over 17 days during the lockdown. The Generalized Anxiety Disorder-7 and Maslach Burnout Inventory were used to assess for anxiety and burnout, respectively. Self-reported fears related to COVID-19 were collected. RESULTS: A total of 624 patients, 408 caregivers, and 421 HCWs participated in the study, with a response rate of 84%, 88%, and 92% respectively. Sixty-six percent of patients, 72.8% of caregivers, and 41.6% of HCWs reported a high level of fear from COVID-19. The top concern of patients was the wide community spread of COVID-19. Caregivers were primarily worried about patients dying alone. HCWs were most worried about the relatively mild symptoms of COVID-19. The prevalence of anxiety was 19.1%, 22.5%, and 14.0% for patients, caregivers, and HCWs, respectively. Patients who were nongraduates and married, and caregivers who were married were more anxious. The prevalence of burnout in HCWs was 43.5%, with more anxious and fearful HCWs reporting higher burnout rates. CONCLUSION: Fears and anxiety related to COVID-19 are high. Burnout among HCWs is similar to rates reported prepandemic. An individualized approach to target the specific fears of each group will be crucial to maintain the well-being of these vulnerable groups and prevent burnout of HCWs.

Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones.

Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid inhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservation of conformational flexibility also enables efficient secretion to the cell surface. Understanding how bacteria safely handle amyloidogenic polypeptides contribute towards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications.

The effect of lower limb muscle fatigue on obstacle negotiation during walking in older adults.

Tripping over obstacles is a common cause of falls in older adults, and muscle fatigue, which can alter walking patterns, may add to this risk. To date, no study has examined the effect of lower limb muscle fatigue on obstacle negotiation in older adults. 30 older adults (13 women, aged 78.3 [6.2] years) negotiated a 12 m obstacle course, while completing a visual secondary task, under two randomized conditions: rested or fatigued. For the fatigue condition, participants performed a repeated sit-to-stand movement, as fast as possible, until they could no longer continue. Participants then immediately began walking trials. Kinematic and kinetic data were collected on approach to, during, and after crossing a height-adjustable target obstacle (10% and 20% of leg length). Repeated measures ANOVA showed a statistically significant increase in lead limb vertical loading rate after stepping over the 10% obstacle when fatigued, relative to rested (P=0.046). No other significant between-condition differences (>0.05) were observed for the other kinematic variables when negotiating the 10% obstacle. Furthermore, no significant between-condition differences (P>0.05) were observed for any kinetic or kinematic variables when negotiating the 20% obstacle. This study describes a feasible method for investigating the consequences of lower limb muscle fatigue on obstacle crossing. The current finding of increased vertical loading rate when fatigued supports the need for further investigation into the effect of muscle fatigue on gait under different environmental conditions, fatiguing a range of muscles, analyzing a more comprehensive array of kinetic and kinematic measures, and in healthy and clinical populations.

Effects of nonslip socks on the gait patterns of older people when walking on a slippery surface.

BACKGROUND: Slips are a common cause of falls, and nonslip socks have been marketed to prevent slips in older people. However, few studies have investigated the biomechanical and clinical effects of walking in nonslip socks. This study aimed to examine gait parameters in older people walking on a slippery surface wearing nonslip socks compared with standard sock and barefoot conditions. METHODS: Fifteen older people completed five trials of the fast-paced Timed Up and Go test while barefoot and while wearing standard socks and nonslip socks. Kinematic data (step length, heel horizontal velocity at heel strike, and foot-floor angle at heel strike) and clinical data (total Timed Up and Go test time, total number of steps, number of steps in turn, and observed slips, trips, or falls) were collected. RESULTS: Performance on the Timed Up and Go test did not differ between the barefoot and nonslip sock conditions; however, participants walked more slowly and took shorter steps when wearing standard socks. Participants rated nonslip socks to feel less slippery than barefoot and standard socks. CONCLUSIONS: Compared with wearing standard socks, wearing nonslip socks improves gait performance and may be beneficial in reducing the risk of slipping in older people.

Efficient assembly and secretion of recombinant subviral particles of the four dengue serotypes using native prM and E proteins.

BACKGROUND: Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process. Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prM and E. METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. A stable HeLa cell line expressing DV1 prME was established (HeLa-prME) and RSPs were analyzed by immunofluorescence and transmission electron microscopy. We found that E protein is mainly present in the endoplasmic reticulum (ER) where assembly of RSPs could be observed. Biochemical characterization of DV1 RSPs secretion revealed both prM protein cleavage and homodimerization of E proteins before their release into the supernatant, indicating that RSPs undergo a similar maturation process as dengue virus. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Knockdown of 23 genes resulted in a significant reduction in DV RSP secretion, whereas for 22 others we observed an increase of RSP levels in cell supernatant. CONCLUSIONS/SIGNIFICANCE: Our data describe the efficient production of RSPs containing native prM and E envelope proteins for all dengue serotypes. Dengue RSPs and corresponding producing cell lines are safe and novel tools that can be used in the study of viral egress as well as in the development of vaccine and drugs against dengue virus.