A Validated Smartphone-Based Assessment of Gait and Gait Variability in Parkinson’s Disease

Background

A well-established connection exists between increased gait variability and greater fall likelihood in Parkinson’s disease (PD); however, a portable, validated means of quantifying gait variability (and testing the efficacy of any intervention) remains lacking. Furthermore, although rhythmic auditory cueing continues to receive attention as a promising gait therapy for PD, its widespread delivery remains bottlenecked. The present paper describes a smartphone-based mobile application (“SmartMOVE”) to address both needs.

Methods

The accuracy of smartphone-based gait analysis (utilizing the smartphone’s built-in tri-axial accelerometer and gyroscope to calculate successive step times and step lengths) was validated against two heel contact–based measurement devices: heel-mounted footswitch sensors (to capture step times) and an instrumented pressure sensor mat (to capture step lengths). 12 PD patients and 12 age-matched healthy controls walked along a 26-m path during self-paced and metronome-cued conditions, with all three devices recording simultaneously.

Results

Four outcome measures of gait and gait variability were calculated. Mixed-factorial analysis of variance revealed several instances in which between-group differences (e.g., increased gait variability in PD patients relative to healthy controls) yielded medium-to-large effect sizes (eta-squared values), and cueing-mediated changes (e.g., decreased gait variability when PD patients walked with auditory cues) yielded small-to-medium effect sizes—while at the same time, device-related measurement error yielded small-to-negligible effect sizes.

Conclusion

These findings highlight specific opportunities for smartphone-based gait analysis to serve as an alternative to conventional gait analysis methods (e.g., footswitch systems or sensor-embedded walkways), particularly when those methods are cost-prohibitive, cumbersome, or inconvenient.     

Interneuronal Mechanism for Tinbergen’s Hierarchical Model of Behavioral Choice

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Precipitation Increases the Occurrence of Sporadic Legionnaires’ Disease in Taiwan

Legionnaires’ disease (LD) is an acute form of pneumonia, and changing weather is considered a plausible risk factor. Yet, the relationship between weather and LD has rarely been investigated, especially using long-term daily data. In this study, daily data was used to evaluate the impacts of precipitation, temperature, and relative humidity on LD occurrence in Taiwan from 1995–2011. A time-stratified 2:1 matched-period case-crossover design was used to compare each case with self-controlled data using a conditional logistic regression analysis, and odds ratios (ORs) for LD occurrence was estimated. The city, gender and age were defined as a stratum for each matched set to modify the effects. For lag day- 0 to 15, the precipitation at lag day-11 significantly affected LD occurrence (p<0.05), and a 2.5% (95% CIs = 0.3–4.7%) increased risk of LD occurrence was associated with every 5-mm increase in precipitation. In addition, stratified analyses further showed that positive associations of precipitation with LD incidence were only significant in male and elderly groups and during the warm season ORs = 1.023–1.029). However, such an effect was not completely linear. Only precipitations at 21–40 (OR = 1.643 (95% CIs = 1.074–2.513)) and 61–80 mm (OR = 2.572 (1.106–5.978)) significantly increased the risk of LD occurrence. Moreover, a negative correlation between mean temperature at an 11-day lag and LD occurrence was also found (OR = 0.975 (0.953–0.996)). No significant association between relative humidity and LD occurrence was identified (p>0.05). In conclusion, in warm, humid regions, an increase of daily precipitation is likely to be a critical weather factor triggering LD occurrence where the risk is found particularly significant at an 11-day lag. Additionally, precipitation at 21–40 and 61–80 mm might make LD occurrence more likely.     

Mechanism of meiotic recombination in eukaryotes—A theory

It is proposed that in meiotic chromosomes single strand breaks of DNA originate either in the delayed regions of replicons or as a result of the excision activity of DNA polymerase during zygotene DNA synthesis. Rejoining of the break points belonging to non-sister chromatids takes place by switching over of the polymerase from one strand of DNA to another non-sister strand of the same polarity and gives rise to recombination intermediates (half-chromatid chiasmata). Strand migration in a recombination intermediate or copying of the same parental strand twice during zygotene as a consequence of a delay in copying the homologous strand would lead to gene conversion. Nicking of the cross strands (parental strands) in any recombination intermediate and subsequent repair leads to recombination for flanking markers. A possible way in which three-strand double crossovers occur and the process of recombination are discussed.     

How Does Dog-Walking Influence Perceptions of Health and Wellbeing in Healthy Adults? A Qualitative Dog-Walk-Along Study

The aim of this study was to explore perceptions of health and wellbeing related to dog-walking in healthy adults. Ten self-reported healthy adult dog-walkers took part in one dog-walk-along interview, and nine of the 10 participants also attended one follow-up participatory analysis session. All interviews took place within the metropolitan area of Dunedin, Aotearoa/New Zealand. Dog-walk-along interviews were participant-led, audio and video recorded, and transcribed. Participants’ input into the inductive generation of themes was sought during the follow-up participatory analysis session. Three themes were identified: participants had an “Emotional Connection” with their dog(s); dog-walking led to “Healthy Interactions” (social and environmental interactions); and participants had come to value dog-walking for its aggregate benefits for Psychological Wellbeing. Our dog-walk-along interviews have revealed novel insights about how the emotional connection between human and dog strengthens intrinsic motivation to exercise (through dog-walking) whilst concurrently enhancing human psychological wellbeing through the act of giving something that gives pleasure to the dog. Through the combined methods of dog-walk-along interviews and participatory analysis sessions, we were able to identify negative influences on human psychological well-being that included anxiety about both dog behaviors and social encounters with other humans. Positive and negative aspects of dog-walking that we identified can be used by health promotion advocates to refine dog-walking related advice, programs, and initiatives.     

Mechanisms of Neural and Behavioral Dysfunction in Alzheimer’s Disease

This review critically examines progress in understanding the link between Alzheimer’s disease (AD) molecular pathogenesis and behavior, with an emphasis on the impact of amyloid-β. We present the argument that the AD research field requires more multifaceted analyses into the impacts of Alzheimer’s pathogenesis which combine simultaneous molecular-, circuit-, and behavior-level approaches. Supporting this argument is a review of particular research utilizing similar, “systems-level” methods in mouse models of AD. Related to this, a critique of common physiological and behavioral models is made—highlighting the likely usefulness of more refined and specific tools in understanding the relationship between candidate molecular pathologies and behavioral dysfunction. Finally, we propose challenges for future research which, if met, may greatly extend our current understanding of how AD molecular pathology impacts neural network function and behavior and possibly may lead to refinements in disease therapeutics.     

Freezing of Gait in Parkinson’s Disease: An Overload Problem?

Freezing of gait (FOG) is arguably the most severe symptom associated with Parkinson’s disease (PD), and often occurs while performing dual tasks or approaching narrowed and cluttered spaces. While it is well known that visual cues alleviate FOG, it is not clear if this effect may be the result of cognitive or sensorimotor mechanisms. Nevertheless, the role of vision may be a critical link that might allow us to disentangle this question. Gaze behaviour has yet to be carefully investigated while freezers approach narrow spaces, thus the overall objective of this study was to explore the interaction between cognitive and sensory-perceptual influences on FOG. In experiment #1, if cognitive load is the underlying factor leading to FOG, then one might expect that a dual-task would elicit FOG episodes even in the presence of visual cues, since the load on attention would interfere with utilization of visual cues. Alternatively, if visual cues alleviate gait despite performance of a dual-task, then it may be more probable that sensory mechanisms are at play. In compliment to this, the aim of experiment#2 was to further challenge the sensory systems, by removing vision of the lower-limbs and thereby forcing participants to rely on other forms of sensory feedback rather than vision while walking toward the narrow space. Spatiotemporal aspects of gait, percentage of gaze fixation frequency and duration, as well as skin conductance levels were measured in freezers and non-freezers across both experiments. Results from experiment#1 indicated that although freezers and non-freezers both walked with worse gait while performing the dual-task, in freezers, gait was relieved by visual cues regardless of whether the cognitive demands of the dual-task were present. At baseline and while dual-tasking, freezers demonstrated a gaze behaviour that neglected the doorway and instead focused primarily on the pathway, a strategy that non-freezers adopted only when performing the dual-task. Interestingly, with the combination of visual cues and dual-task, freezers increased the frequency and duration of fixations toward the doorway, compared to non-freezers. These results suggest that although increasing demand on attention does significantly deteriorate gait in freezers, an increase in cognitive demand is not exclusively responsible for freezing (since visual cues were able to overcome any interference elicited by the dual-task). When vision of the lower limbs was removed in experiment#2, only the freezers’ gait was affected. However, when visual cues were present, freezers’ gait improved regardless of the dual-task. This gait behaviour was accompanied by greater amount of time spent looking at the visual cues irrespective of the dual-task. Since removing vision of the lower-limbs hindered gait even under low attentional demand, restricted sensory feedback may be an important factor to the mechanisms underlying FOG.     

Pulsed Electromagnetic Fields Improve Bone Microstructure and Strength in Ovariectomized Rats through a Wnt/Lrp5/β-Catenin Signaling-Associated Mechanism

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.     

Balance Asymmetry in Parkinson’s Disease and Its Contribution to Freezing of Gait

Balance control (the ability to maintain an upright posture) is asymmetrically controlled in a proportion of patients with Parkinson’s disease. Gait asymmetries have been linked to the pathophysiology of freezing of gait. We speculate that asymmetries in balance could contribute to freezing by a) hampering the unloading of the stepping leg and/or b) leading to a preferred stance leg during gait, which then results in asymmetric gait. To investigate this, we examined the relationship between balance control and weight-bearing asymmetries and freezing. We included 20 human patients with Parkinson (tested OFF medication; nine freezers) and nine healthy controls. Balance was perturbed in the sagittal plane, using continuous multi-sine perturbations, applied by a motion platform and by a force at the sacrum. Applying closed-loop system identification techniques, relating the body sway angle to the joint torques of each leg separately, determined the relative contribution of each ankle and hip joint to the total amount of joint torque. We also calculated weight-bearing asymmetries. We determined the 99-percent confidence interval of weight-bearing and balance-control asymmetry using the responses of the healthy controls. Freezers did not have larger asymmetries in weight bearing (p = 0.85) nor more asymmetrical balance control compared to non-freezers (p = 0.25). The healthy linear one-to-one relationship between weight bearing and balance control was significantly different for freezers and non-freezers (p = 0.01). Specifically, non-freezers had a significant relationship between weight bearing and balance control (p = 0.02), whereas this relation was not significant for freezers (p = 0.15). Balance control is asymmetrical in most patients (about 75 percent) with Parkinson’s disease, but this asymmetry is not related to freezing. The relationship between weight bearing and balance control seems to be less pronounced in freezers, compared to healthy controls and non-freezers. However, this relationship should be investigated further in larger groups of patients.     

Seasonal Incidence of Medically Attended Respiratory Syncytial Virus Infection in a Community Cohort of Adults ≥50 Years Old

Background

Diagnostic testing for respiratory syncytial virus (RSV) is not routinely performed in adults. We estimated medically attended RSV seasonal incidence in a community cohort of adults ≥50 years old during four influenza seasons (2006–07 through 2009–10).

Methods

Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR. Results from enrolled patients were used to estimate projected cases among non-enrolled patients with ARI. The seasonal incidence of medically attended RSV was the sum of actual and projected cases divided by the community cohort denominator. Since each enrollment period did not include the entire RSV season, incidence estimates were adjusted to account for the statewide proportion of RSV occurring outside the study enrollment period.

Results

There were 16,088 to 17,694 adults in the cohort each season and 164 RSV cases in all 4 seasons. The overall seasonal incidence of medically attended RSV was 154 episodes (95% CI, 132–180) per 10,000 persons; the incidence was highest in 2007–08 (179) and lowest in 2006–07 (110). Among persons 50–59, 60–69, and ≥70 years old, RSV incidence was 124 (95% CI, 99–156), 147 (95% CI, 110–196), and 199 (95% CI, 153–258), respectively.

Conclusions

The incidence of medically attended RSV increased with age and was similar during four seasons.     

Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity

The Alzheimer’s disease neurotoxic amyloid-β (Aβ) peptide is derived from the larger amyloid precursor protein (APP) and is the principal component of the senile plaques in Alzheimer’s disease (AD) brains. This mechanism by which Aβ mediates neurotoxicity or neuronal dysfunction is not fully resolved. This review will outline some of the key determinants that modulate Aβ’s activity and the cellular pathways and mechanisms involved.     

A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population

The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5''-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c._-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c._-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c._-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19–93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38–9.55; p = 0.44). Co-occurrence of the genotypes -/- of c._-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C._-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p<0.01). Both co-immunoprecipitation and in vitro protein pull-down assays demonstrated that δ-SG-283R interacts normally to β- and γ-SG, but significantly decreased localization of β/δ/γ-SG on the plasma membrane. In conclusion, haplotype -_G composed of c._-100~-110 and A848G confers higher susceptibility to DCM in the Mongoloid population.     

Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson’s Disease with Freezing of Gait

Background

Patients with Parkinson’s disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation.

Objective

To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting.

Methods

Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes.

Results

Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group.

Conclusions

Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols.     

Men’s Physical Strength Moderates Conceptualizations of Prospective Foes in Two Disparate Societies

Across taxa, strength and size are elementary determinants of relative fighting capacity; in species with complex behavioral repertoires, numerous additional factors also contribute. When many factors must be considered simultaneously, decision-making in agonistic contexts can be facilitated through the use of a summary representation. Size and strength may constitute the dimensions used to form such a representation, such that tactical advantages or liabilities influence the conceptualized size and muscularity of an antagonist. If so, and given the continued importance of physical strength in human male-male conflicts, a man’s own strength will influence his conceptualization of the absolute size and strength of an opponent. In the research reported here, male participants’ chest compression strength was compared with their estimates of the size and muscularity of an unfamiliar potential antagonist, presented either as a supporter of a rival sports team (Study 1, conducted in urban California, and Study 2, conducted in rural Fiji) or as a man armed with a handgun (Study 3, conducted in rural Fiji). Consistent with predictions, composite measures of male participants’ estimates of the size/strength of a potential antagonist were inversely correlated with the participant’s own strength. Therefore, consonant with a history wherein violent intrasexual selection has acted on human males, a man’s own physical strength influences his representations of potential antagonists.     

Risk of Shingles in Adults with Primary Sjogren’s Syndrome and Treatments: A Nationwide Population-Based Cohort Study

Background

Primary Sjögren''s syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.

Methods

This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.

Results

During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.

Conclusions

Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.     

Role of the Earth’s Motions in Plant Orientation – Planetary Mechanism

Biochemistry (Moscow) - According to the proposed theory, the starch-rich particles (statoliths) help the plant to convert the signals from Earth’s motions into the signals necessary for the...     

Birth Month and Risk of Glioma in Adults: A Registry‐Based Study in Bavaria

The aim of the present study was to evaluate the possible seasonality of birth in adult patients suffering from glioma. For this purpose, data from the database of the population‐based cancer registry of Bavaria (Germany) were retrieved. For the period 2002–2005, we identified a total of 2174 patients born between 1931 and 1986 diagnosed with malignant glioma. Statistical analyses failed to document a significant annual periodicity of glioma risk in either men or women with respect to birth month in the observed cohort. Thus, we found no association between month of birth and the risk of glioma. In contrast, an analysis of the official birth rate data of Bavaria revealed marked annual variation in birth rates up until 1965, which decreased markedly in prominence in the years thereafter. Our findings confirm the results of a recent similar study conducted in The Netherlands. Therefore, we support the hypothesis of possible etiological factors of glioma acting in adulthood rather than in the perinatal period.     

The Gait Deviation Index Is Associated with Hip Muscle Strength and Patient-Reported Outcome in Patients with Severe Hip Osteoarthritis—A Cross-Sectional Study

BackgroundThe Gait Deviation Index summarizes overall gait ‘quality’, based on kinematic data from a 3-dimensional gait analysis. However, it is unknown which clinical outcomes may affect the Gait Deviation Index in patients with primary hip osteoarthritis. The aim of this study was to investigate associations between Gait Deviation Index as a measure of gait ‘quality’ and hip muscle strength and between Gait Deviation Index and patient-reported outcomes in patients with primary hip osteoarthritis.MethodForty-seven patients (34 males), aged 61.1 ± 6.7 years, with BMI 27.3 ± 3.4 (kg/m²) and with severe primary hip osteoarthritis underwent 3-dimensional gait analysis. Mean Gait Deviation Index, pain after walking and maximal isometric hip muscle strength (flexor, extensor, and abductor) were recorded. All patients completed the ‘Physical Function Short-form of the Hip disability and Osteoarthritis Outcome Score (HOOS-Physical Function) and the Hip disability and Osteoarthritis Outcome Score subscales for pain (HOOS-Pain) and quality-of-life (HOOS-QOL).ResultsMean Gait Deviation Index was positively associated with hip abduction strength (p<0.01, r = 0.40), hip flexion strength (p = 0.01, r = 0.37), HOOS-Physical Function (p<0.01, r = 0.41) HOOS-QOL (p<0.01, r = 0.41), and negatively associated with HOOS-Pain after walking (p<0.01, r = -0.45). Adjusting the analysis for walking speed did not affect the association.ConclusionPatients with the strongest hip abductor and hip flexor muscles had the best gait ‘quality’. Furthermore, patients with higher physical function, quality of life scores and lower pain levels demonstrated better gait ‘quality’. These findings indicate that interventions aimed at improving hip muscle strength and pain management may to a moderate degree improve the overall gait ‘quality’ in patients with primary hip OA.