Jeffrey L. Alexander

Balancing with Vibration: A Prelude for “Drift and Act” Balance Control

Stick balancing at the fingertip is a powerful paradigm for the study of the control of human balance. Here we show that the mean stick balancing time is increased by about two-fold when a subject stands on a vibrating platform that produces vertical vibrations at the fingertip (0.001 m, 15–50 Hz). High speed motion capture measurements in three dimensions demonstrate that vibration does not shorten the neural latency for stick balancing or change the distribution of the changes in speed made by the fingertip during stick balancing, but does decrease the amplitude of the fluctuations in the relative positions of the fingertip and the tip of the stick in the horizontal plane, A(x,y). The findings are interpreted in terms of a time-delayed “drift and act” control mechanism in which controlling movements are made only when controlled variables exceed a threshold, i.e. the stick survival time measures the time to cross a threshold. The amplitude of the oscillations produced by this mechanism can be decreased by parametric excitation. It is shown that a plot of the logarithm of the vibration-induced increase in stick balancing skill, a measure of the mean first passage time, versus the standard deviation of the A(x,y) fluctuations, a measure of the distance to the threshold, is linear as expected for the times to cross a threshold in a stochastic dynamical system. These observations suggest that the balanced state represents a complex time–dependent state which is situated in a basin of attraction that is of the same order of size. The fact that vibration amplitude can benefit balance control raises the possibility of minimizing risk of falling through appropriate changes in the design of footwear and roughness of the walking surfaces.

Elevated Alpha-Synuclein Impairs Innate Immune Cell Function and Provides a Potential Peripheral Biomarker for Parkinson's Disease

Alpha-synuclein protein is strongly implicated in the pathogenesis Parkinsons disease. Increased expression of α-synuclein due to genetic multiplication or point mutations leads to early onset disease. While α-synuclein is known to modulate membrane vesicle dynamics, it is not clear if this activity is involved in the pathogenic process or if measurable physiological effects of α-synuclein over-expression or mutation exist in vivo. Macrophages and microglia isolated from BAC α-synuclein transgenic mice, which overexpress α-synuclein under regulation of its own promoter, express α-synuclein and exhibit impaired cytokine release and phagocytosis. These processes were affected in vivo as well, both in peritoneal macrophages and microglia in the CNS. Extending these findings to humans, we found similar results with monocytes and fibroblasts isolated from idiopathic or familial Parkinsons disease patients compared to age-matched controls. In summary, this paper provides 1) a new animal model to measure α-synuclein dysfunction; 2) a cellular system to measure synchronized mobilization of α-synuclein and its functional interactions; 3) observations regarding a potential role for innate immune cell function in the development and progression of Parkinsons disease and other human synucleinopathies; 4) putative peripheral biomarkers to study and track these processes in human subjects. While altered neuronal function is a primary issue in PD, the widespread consequence of abnormal α-synuclein expression in other cell types, including immune cells, could play an important role in the neurodegenerative progression of PD and other synucleinopathies. Moreover, increased α-synuclein and altered phagocytosis may provide a useful biomarker for human PD.

Relative distribution of West Nile virus RNA in blood compartments: implications for blood donor nucleic acid amplification technology screening

BACKGROUND: Despite implementation of targeted individual‐donor nucleic acid test (NAT) screening of blood donors for West Nile virus (WNV), three “breakthrough” WNV transfusion transmission cases were reported (2004‐2008), suggesting that current plasma‐based assays are unable to detect all WNV‐infectious donations. A 2007 report found that 19 of 20 red blood cell components from WNV‐infected donors contained 1 log higher viral load than plasma components. This studys aim was to further establish the value of screening whole blood relative to plasma for WNV RNA by generating differential viral loads on paired samples derived from blood screening tubes.

Validation of functional fitness tests as surrogates for strength measurement in frail, older adults with chronic obstructive pulmonary disease.

Benton MJ, Alexander JL: Validation of functional fitness tests as surrogates for strength measurement in frail, older adults with COPD. Am J Phys Med Rehabil 2009;88:579–586. Objective:This study evaluated the relationship of functional field tests to traditional laboratory strength tests in 40 frail, older adults with chronic obstructive pulmonary disease. Design:Participants completed two trials of upper (chest press) and lower (leg press) body maximal strength (maximal weight lifted one time) testing and one trial of functional fitness testing (Arm Curl, Lift and Reach, Chair Stand, Up and Go). The maximal weight lifted one-time values from both trials were compared with functional fitness test values to identify valid surrogates. Results:Among upper-body functional fitness tests, the Arm Curl had a moderately strong relationship to chest press (trial 1: r = 0.55, P = 0.01; trial 2: r = 0.56, P = 0.01) whereas the Lift and Reach did not. Among lower-body functional fitness tests, the Chair Stand had a fairly strong relationship to leg press (trial 1: r = 0.46, P = 0.01; trial 2: r = 0.38, P = 0.05), but the Up and Go did not. Conclusions:Only the Arm Curl and Chair Stand tests were valid surrogates. Although multiple field tests to measure strength in a clinical setting may be desirable, these data support limiting functional testing to the Arm Curl for upper-body and the Chair Stand for lower-body strength assessment.

Relationship between body mass index, nutrition, strength, and function in elderly individuals with chronic obstructive pulmonary disease.

PURPOSE: Individuals with severe chronic obstructive pulmonary disease are frequently characterized as cachectic and suffering from generalized weight loss and muscle wasting. Loss of body mass is associated with disability and premature mortality, and body mass index (BMI) has been used as a marker for nutritional status and to predict survival. This cross-sectional study evaluated the association between BMI (kg/m2), nutritional intake, strength, and function in 19 elderly (70 ± 1 years) men and women (BMI = 27.8 ± 1.1 kg/m2) enrolled in a pulmonary rehabilitation program. METHODS: Three-day prospective diet records were collected and analyzed using Food Processor software. Upper and lower body strength was measured using 1 repetition maximum testing for chest and leg press. Function (endurance, strength, and power) was assessed using the Senior Fitness Test battery (6-minute walk, up-and-go, chair stand, arm curl). RESULTS: BMI was positively associated with upper (P < .05) and lower (P < .01) body strength but was not related to nutrition or function. Total daily caloric (kcal/d), protein (g/d), and carbohydrate (g/d) intakes were positively related to upper body strength (P < .01, P < .01, and P < .05, respectively) and lower body strength (P < .05, P < .05, and P < .05, respectively) and 6-minute walk (P < .05). Fat intake (g/d) was positively related to upper body strength (P < 0.05) alone. CONCLUSIONS: Despite health concerns regarding obesity and overweight, clinicians should consider the impact of BMI and dietary intake before initiating weight loss interventions in patients with chronic obstructive pulmonary disease.

Femoral Neck Stress Fracture in Air Force Basic Trainees

Stress fractures are a common overuse problem among military trainees resulting in preventable morbidity, prolonged training, and long-term disability following military service. Femoral neck stress fractures (FNSFs) account for 2% of all stress fractures but result in disproportionate burden in terms of cost and convalescence. The purpose of this study was to describe and investigate FNSF in U.S. Air Force basic trainees and to present new data on risks factors for developing FNSF. We examined 47 cases of FNSF occurring in Air Force basic trainees between 2008 and 2011 and 94 controls using a matched case-control model. Analysis with t tests and conditional logistic regression found the risk of FNSF was not associated with body mass index or abdominal circumference. Female gender (p < 0.001) and slower run time significantly increased risk of FNSF (1.49 OR, p < 0.001; 95% CI 1.19-1.86). A greater number of push-up and sit-up repetitions significantly reduced risk of FNSF (0.55 OR, p = 0.03; 95% CI 0.32-0.93; 0.62 OR, p = 0.04; 95% CI 0.4-0.98) for females. In this study body mass index was not correlated with FNSF risk; however, physical fitness level on arrival to training and female gender were significantly associated with risk of FNSF.

Relationship between strength, function, and quality of life in older adults with chronic lung disease: is there an influence of gender?

PURPOSE: Chronic lung disease results in impaired quality of life (QOL) linked to loss of muscular strength and functional ability. Inequalities in strength and function may place women at greater risk than men. This study evaluated the influence of gender on the relationship between muscular strength, functional ability, and QOL. METHODS: Older adults (N = 40) referred to a pulmonary rehabilitation program completed assessment of upper body and lower body strength, functional ability, and QOL. To compensate for gender differences, strength was normalized for body mass. RESULTS: Strength was greater in men than in women (P < .001). No gender differences were observed for function. Men perceived better QOL related to physical function (score: 39.3 ± 3.3 vs 27.1 ± 2.1, P < .01) and social function (score: 58.0 ± 5.8 vs 41.6 ± 4.0, P < .05). In men, strength was related directly to QOL through physical function (r = 0.53, P < .05) and social function (r = 0.52, P < .05), and functional ability had no relationship to QOL. In women, strength was related to functional ability (r = 0.57, P < .05), and functional ability was directly related to QOL through physical function (r = 0.46, P < .05), and social function (r = 0.59, P < .01). CONCLUSIONS: Functional ability mediates the relationship between strength and QOL in women, while in men strength is directly related to QOL. These gender-specific pathways to QOL may be of importance to clinicians planning interventions for older adults with chronic lung disease.

SNAP Participation in Preschool-Aged Children and Prevalence of Overweight and Obesity.

BACKGROUND An increased prevalence of overweight and obesity for adults on government-funded nutrition assistance, such as the Supplemental Nutrition Assistance Program (SNAP), has been observed; however, this association among preschool-aged children is not well understood. Longitudinal research designs tracking changes in body mass index-for-age (BMI) in children of low-income households may provide a clearer picture of the association between SNAP participation and overweight and obesity among this age group. To determine if there is a relationship between SNAP participation and overweight and obesity prevalence in low-income, preschool children, we conducted a cross-sectional analysis of children in a Head Start program, and a longitudinal analysis of those children who were enrolled for 2 years. METHODS Height and weight data and SNAP participation of 386 students (207 male, 179 female, 4.2 ± 0.5 years) enrolled in a Head Start program were analyzed; data for 2 years were available for 167 of the students. Height and weight measures were used to determine BMI percentile per Centers for Disease Control and Prevention guidelines. SNAP participation was obtained through a nutritional questionnaire given to parents at time of Head Start Program enrollment. RESULTS No significant differences were found between SNAP and non-SNAP participants for BMI percentile in either the cross-sectional or longitudinal analysis. BMI percentile increased for both groups over time, but failed to reach significance (p = .13). CONCLUSION Future studies are warranted with an inclusion of a larger and more geographically diverse sample to further determine the association between SNAP participation and overweight and obesity in preschool-aged children.

Is Harmonica Playing an Effective Adjunct Therapy to Pulmonary Rehabilitation

Purpose: This randomized controlled trial examined the effect harmonica playing has on various clinical, psychosocial, and functional outcomes among chronic obstructive pulmonary disease (COPD) patients in pulmonary rehabilitation (PR). Method: Twenty‐eight participants (Age 69.9 ± 1.8; FEV1 Predicted 41.9 ± 2.0%) were recruited from an outpatient PR program. Participants were randomly assigned to one of two groups, traditional PR (C; n = 16) or traditional PR plus harmonica playing (HT; n = 9). The HT group was provided a harmonica and one‐on‐one instruction by PR staff. Patients were given practice exercises to perform for at least 5 minutes, but not exceeding 20 minutes twice/day, 5 days/week. Results: No significant differences were found between groups. The combined sample improved significantly in their perception of shortness of breath, quality of life, and distance walked in 6 minutes. Conclusion: Harmonica playing does not significantly affect the clinical, psychosocial, or functional status of COPD patients enrolled in PR.

Caregivers' beliefs associated with medication adherence among children and adolescents with epilepsy.

ABSTRACTThe purpose of this study was to determine the association between adherence to prescribed antiepileptic medication in a convenience sample of caregivers (n = 100) of children diagnosed with epilepsy, ages 2–14 years, and caregivers’ beliefs about the medication. Using the Beliefs about Medication Questionnaire and Medication Adherence Report Scale, caregivers were questioned about beliefs of necessity and concerns associated with medication adherence. Using bivariate linear regression, no significant correlation was found between necessity for antiepileptic drug treatment or caregiver’s concerns and medication adherence. Nevertheless, although only 28% of the respondents reported complete adherence, the majority of caregivers perceived their child’s medication was necessary to maintain good health. Educational aspects and social desirability in this setting may have contributed to the discordance between adherence and caregivers’ beliefs.