Nonlinear analysis of human physical activity patterns in health and disease.

The reliable and objective assessment of chronic disease state has been and still is a very significant challenge in clinical medicine. An essential feature of human behavior related to the health status, the functional capacity, and the quality of life is the physical activity during daily life. A common way to assess physical activity is to measure the quantity of body movement. Since human activity is controlled by various factors both extrinsic and intrinsic to the body, quantitative parameters only provide a partial assessment and do not allow for a clear distinction between normal and abnormal activity. In this paper, we propose a methodology for the analysis of human activity pattern based on the definition of different physical activity time series with the appropriate analysis methods. The temporal pattern of postures, movements, and transitions between postures was quantified using fractal analysis and symbolic dynamics statistics. The derived nonlinear metrics were able to discriminate patterns of daily activity generated from healthy and chronic pain states.

Subclinical hypothyroidism and functional mobility in older adults.

BACKGROUND: Health risks associated with subclinical hypothyroidism in older adults are unclear. Our objective was to compare the functional mobility of people aged 70 to 79 years by thyroid function categorized by thyrotropin (TSH) level as euthyroid (>or=0.4 to <4.5 mIU/L), mild subclinical hypothyroid (>or=4.5 to <7.0 mIU/L), or moderate subclinical hypothyroid (>or=7.0 to <or=20.0 mIU/L with a normal free thyroxine level) cross-sectionally and over 2 years. METHODS: A total of 2290 community-dwelling residents participating in the year 2 clinic visit (July 1998-June 1999) of the Health, Aging, and Body Composition (Health ABC) Study, who had measured TSH level, had the capacity to walk 20 m unaided, and were not taking thyroid medication or had TSH levels consistent with hyperthyroidism or hypothyroidism. Main outcome measures included self-reported and performance-based measures of mobility (usual and rapid gait speed and endurance walking ability) assessed at study baseline (year 2) and 2 years later. RESULTS: In age- and sex-adjusted analyses, the mild subclinical hypothyroid group (vs the euthyroid group) demonstrated better mobility (faster mean usual and rapid gait speed [1.20 vs 1.15 m/s and 1.65 vs 1.56 m/s, respectively; P < .001] and had a higher percentage of those with good cardiorespiratory fitness and reported walking ease [39.2% vs 28.0% and 44.7% vs 36.5%, respectively; P < .001]). After 2 years, persons with mild subclinical hypothyroidism experienced a similar decline as the euthyroid group but maintained their mobility advantage. Persons with moderate subclinical hypothyroidism had similar mobility and mobility decline as the euthyroid group. CONCLUSION: Generally, well-functioning 70- to 79-year-old individuals with subclinical hypothyroidism do not demonstrate increased risk of mobility problems, and those with mild elevations in TSH level show a slight functional advantage.

Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay.

Although p53-gene mutations occur with significant frequency in diffuse low-grade and high-grade astrocytomas, and are postulated to play an important role in tumorigenesis in these cases, the role of the p53 gene in pilocytic astrocytomas remains unclear. Published data using DNA-based assays for p53-gene analysis in these tumors have shown contradictory results in mutation frequency (0-14%). It is not known whether these heterogeneous results stem from the biological diversity of this tumor group or from technical problems. To re-evaluate p53-gene status in pilocytic tumors, we analyzed 18 tumors chosen to represent the clinical and biological heterogeneity of this tumor type with respect to anatomical location, patient age, gender, ethnic origin (Caucasian or Japanese) and the concomitant occurrence of neurofibromatosis type 1 (NF1). All primary tumors were histologically diagnosed as pilocytic astrocytoma (WHO grade I), except for one anaplastic pilocytic astrocytoma (WHO grade III) which developed in an NF1 patient and recurred as glioblastoma multiforme (WHO grade IV). p53 mutations were detected using an assay in yeast which tests the transcriptional activity of p53 proteins synthesized from tumor mRNA-derived p53-cDNA templates. None of 18 tumors, including 3 NF1-related tumors, showed p53-gene mutations between and including exons 4 and 11. We conclude that p53-gene mutations are extremely rare findings in pilocytic astrocytomas, and are absent even in those exceptional cases in which malignant progression of such tumors has occurred.

Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. They encoded two different forms of the receptor, which differed by a 27-amino acid insertion in the COOH-terminal cytoplasmic tail. The receptor protein sequence was 81% identical to that of the rat GIP receptor. When expressed in Chinese hamster lung fibroblasts, both forms of the receptor displayed high-affinity binding for GIP (180 and 600 pmol/l). GIP binding was displaced by &lt; 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. However exendin-4 and exendin-(9-39) at 1 mumol/l displaced binding by approximately 70 and approximately 100% at 10 mumol/l. GIP binding to both forms of the receptor induced a dose-dependent increase in intracellular cAMP levels (EC50 values of 0.6-0.8 nmol/l) but no elevation of cytoplasmic calcium concentrations. Interestingly, both exendin-4 and exendin-(9-39) were antagonists of the receptor, inhibiting GIP-induced cAMP formation by up to 60% when present at a concentration of 10 mumol/l. Finally, the physical and genetic chromosomal localization of the receptor gene was determined to be on 19q13.3, close to the ApoC2 gene. These data will help study the physiology and pathophysiology of the human GIP receptor.

Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia.

Continuous monitoring and quantification of multiple parameters of daily physical activity in ambulatory Duchenne muscular dystrophy patients.

Multiple motor function and strength assessment tools exist for the evaluation of neuromuscular diseases, but most do not directly assess functional ability in the patients' daily physical activity in their home environment. In this study our aim was to assess: 1) the feasibility and accuracy of physical activity monitoring during two days in a home environment of five DMD patients using a non-commercialized monitor containing a 3D accelerometer and a gyroscope, 2) if a difference in the physical activity parameters could be measured before and one month after starting prednisolone. We reliably quantified the time spend sitting, standing, lying, walking, the number of steps taken, the cadence, the number of walking episodes and their duration as well as how these were distributed over the day. Parameters possibly reflecting endurance, such as the duration of the walking episodes or the succession of two or three walking episodes lasting more than 30 s were the most improved after prednisolone treatment. This degree of detailed determination of physical activity in a home environment has not been previously reported in neuromuscular disorders to our knowledge and some of the reported parameters are potential new outcome measures in clinical trials.

Predictors of functional recovery in patients admitted to geriatric postacute rehabilitation.

OBJECTIVE: To examine characteristics associated with functional recovery in older patients undergoing postacute rehabilitation. DESIGN: Observational study. SETTING: Postacute rehabilitation facility. PARTICIPANTS: Patients (N=2754) aged ≥65 years admitted over a 4-year period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Functional status was assessed at admission and again at discharge. Functional recovery was defined as achieving at least 30% improvement on the Barthel Index score from admission compared with the maximum possible room for improvement. RESULTS: Patients who achieved functional recovery (70.3%) were younger and were more likely to be women, live alone, and be without any formal home care before admission, and they had fewer chronic diseases (all P<.01). They also had better cognitive status and a higher Barthel Index score both at admission (mean ± SD, 63.3±18.0 vs 59.6±24.7) and at discharge (mean ± SD, 86.8±10.4 vs 62.2±22.9) (all P<.001). In multivariate analysis, patients <75 years of age (adjusted odds ratio [OR]=1.51; 95% confidence interval [CI], 1.16-1.98; P=.003), women (adjusted OR=1.24; 95% CI, 1.01-1.52; P=.045), patients living alone (adjusted OR=1.61; 95% CI, 1.31-1.98; P<.001), and patients without in-home help prior to admission (adjusted OR=1.39; 95% CI, 1.15-1.69; P=.001) remained at increased odds of functional recovery. In addition, compared with those with moderate-to-severe cognitive impairment (Mini-Mental State Examination score <18), patients with mild-to-moderate impairment (Mini-Mental State Examination score 19-23) and those cognitively intact also had increased odds of functional recovery (adjusted OR=1.56; 95% CI, 1.13-2.15; P=.007; adjusted OR=2.21; 95% CI, 1.67-2.93; P<.001, respectively). CONCLUSIONS: Apart from sociodemographic characteristics, cognition is the strongest factor that identifies older patients more likely to improve during postacute rehabilitation. Further study needs to determine how to best adapt rehabilitation processes to better meet the specific needs of this population and optimize their outcome.

Barriers, benefits and preferences for exercise in RA patients: A cross sectional study.

Background/Purpose: Physical exercise is safe and effective as an adjunctive nonpharmacological treatment modality in the management of rheumatoid arthritis (RA). It is well established that patients with RA are less active compared to healthy controls. The transtheoretical model of health promotion, based on five stages of change, provides a useful framework to better understand patients' motivation towards regular exercise. The purpose of this study was to determine the distribution of exercise stages of change in a RA cohort, and to examine barriers, benefits and preferences for exercise. Methods: One hundred and twenty consecutive patients with RA followed at a hospital-based rheumatology practice were invited to participate in the study. Those who accepted to participate filled in a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. Disease activity was measured using the disease activity score (DAS28). Other variables included the Health Assessment Questionnaire (HAQ), the short version of the Arthritis Impact Measurement Scales 2 (AIMS2-SF), pain and fatigue visual analogue scales (VAS), the number of comorbidities and demographic characteristics. Characteristics of patients in the maintenance and precontemplation stages of change were compared using two-sample t tests, Wilcoxon rank-sum tests and Chi-square tests. Results: Eighty nine (74%) patients were finally included in the analyses. Mean age was 58.4 (SD 11.7) years, mean RA duration was 10.1 (9.8) years and mean DAS28 was 2.8 (1.2). The distribution of exercise stages of change was as follows: precontemplation (n_30, 34%), contemplation (n_11, 13%), preparation (n_5, 6%), action (n_2, 2%), and maintenance (n_39, 45%). Compared to patients in the maintenance stage of change, precontemplators were less often at work (P_0.05), exhibited a higher body mass index (P_0.01), poorer HAQ (P_0.01), higher pain VAS (P_0.05), poorer scores of physical (P_0.001), symptom (P_0.01), affect (P_0.01) and role (P_0.01) dimensions of the AIMS2-SF, and reported less exercise benefits (P_0.05) and more barriers to exercise (p_0.01). Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). Conclusion: This study provides new insight into how RA interferes with exercise participation. Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs in terms of exercise counseling different. Walking appears to be a simple but promising way of promoting physical activity among RA patients.

Effect of intradialytic resistance band exercise on physical function in patients on maintenance hemodialysis: a pilot study.

Although physical activity is recommended in patients on maintenance hemodialysis (MHD), randomized controlled trials testing the effects of exercise in this population have given conflicting results. In general, aerobic exercises mostly failed to produce improvements in physical function, whereas resistance exercises, although less studied, appeared to be more promising. The use of sophisticated materials such as leg press and free weights may preclude widespread application of resistance training in patients on MHD. Simple and cheap elastic bands may thus be an attractive alternative. We tested the feasibility of a supervised intradialytic resistance band exercise training program, and its effects on physical function, in patients on MHD. A total of 11 unselected adult patients on MHD from our center, aged 70 ± 10.7 (mean ± standard deviation) years, including 8 men and 3 women, accepted to follow the program under the supervision of qualified physiotherapists. Thirty-six exercise sessions of moderate intensity (twice a week, mean duration 40 minutes each, during 4.5 to 6 months), mainly involving leg muscles against an elastic resistance, were performed. The exercise program was well tolerated and all patients completed it. Statistically significant improvements were observed in the following tests: Tinetti test, 23.9 ± 3.9 points before versus 25.7 ± 3.5 points after the program (P = .022); the Timed Up and Go test, 12.1 ± 6.6 versus 10 ± 5.8 seconds (P = .0156). Improvements in the 6-minute walk distance and in the one-leg balance tests just failed to reach statistical significance. In this single-center pilot study, an intradialytic resistance band exercise program was feasible, well tolerated, and showed encouraging results on physical function.

Physical determinants of tennis performance in competitive teenage players

It is unclear how physical attributes influence tennis-specific performance in teenage players. The aims of this study were (a) to examine the relationships between speed, explosive power, leg stiffness, and muscular strength of upper and lower limbs; and (b) to determine to what extent these physical qualities relate to tournament play performance in a group of competitive teenage tennis players. A total of 12 male players aged 13.6 +/- 1.4 years performed a series of physical tests: a 5-m, 10-m, and 20-m sprint; squat jump (SJ); countermovement jump (CMJ); drop jump (DJ); multi-rebound jumps; maximum voluntary contraction of isometric grip strength; and plantar flexor of the dominant and nondominant side. Speed (r = 0.69, 0.63, and 0.74 for 5-, 10-, and 20-m sprints, respectively), vertical power abilities (r = -0.71, -0.80 and -0.66 for SJ, CMJ, and DJ, respectively), and maximal strength in the dominant side (r = -0.67 and -0.73 for handgrip and plantar flexor, respectively) were significantly correlated with tennis performance. However, strength in the nondominant side (r = -0.29 and -0.42 for handgrip and plantar flexor) and leg stiffness (r = -0.15) were not correlated with the performance ranking of the players. It seems that physical attributes have a strong influence on tennis performance in this age group and that an important asymmetry is already observed. By monitoring regularly such physical abilities during puberty, the conditioning coach can modify a program to compensate for the imbalances. This would in turn minimize the risks of injuries during this critical period.

Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients.

OBJECTIVES: High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort. METHODS: The Early Psychosis Prevention and Intervention Centre admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. A total of 704 files were available, 43 excluded because of a nonpsychotic diagnosis at end point and 3 due to missing data regarding past stressful events; 658 patients were analyzed. RESULTS: A total of 83% patients had been exposed to at least one stressful event and 34% to SPA. SPA patients were more likely to have presented other psychiatric disorders before psychosis onset (posttraumatic stress disorder, substance use disorder), to have made suicide attempts in the past, and to have had poorer premorbid functional levels. Additionally, SPA patients had higher rate of comorbid diagnosis at program entry and were more likely to attempt suicide during treatment. CONCLUSIONS: SPA prevalence is high in FEP patients and must be explored by clinicians considering its durable impact on psychological balance and link with long-lasting suicidal risk. More research is warranted to better understand mechanisms involved between trauma and its potential consequences, as well as to develop psychological interventions adapted to this very sensitive and complex issue.

Probing functional groups at the gas-aerosol interface using heterogeneous titration reactions: a tool for predicting aerosol health effects?

The complex chemical and physical nature of combustion and secondary organic aerosols (SOAs) in general precludes the complete characterization of both bulk and interfacial components. The bulk composition reveals the history of the growth process and therefore the source region, whereas the interface controls--to a large extent--the interaction with gases, biological membranes, and solid supports. We summarize the development of a soft interrogation technique, using heterogeneous chemistry, for the interfacial functional groups of selected probe gases [N(CH(3))(3), NH(2)OH, CF(3)COOH, HCl, O(3), NO(2)] of different reactivity. The technique reveals the identity and density of surface functional groups. Examples include acidic and basic sites, olefinic and polycyclic aromatic hydrocarbon (PAH) sites, and partially and completely oxidized surface sites. We report on the surface composition and oxidation states of laboratory-generated aerosols and of aerosols sampled in several bus depots. In the latter case, the biomarker 8-hydroxy-2'-deoxyguanosine, signaling oxidative stress caused by aerosol exposure, was isolated. The increase in biomarker levels over a working day is correlated with the surface density N(i)(O3) of olefinic and/or PAH sites obtained from O(3) uptakes as well as with the initial uptake coefficient, γ(0), of five probe gases used in the field. This correlation with γ(0) suggests the idea of competing pathways occurring at the interface of the aerosol particles between the generation of reactive oxygen species (ROS) responsible for oxidative stress and cellular antioxidants.

Neuroendocrine regulation and central dopamine (DA) systems in physical and psychological stress

Physical and psychological stress cause different patterns of changes in the fluorescence intensity of nigral and tuberoinfundibular DA neurons which point to changes in neuronal activity. In order to investigate possible interactions between alpha-MSH (alpha-melanotropin) and DA systems in stress, systemic and intraventricular injections of antiserum against alpha-MSH were made. The functional state of DA neurons was assessed by histochemical microfluorimetry and hormone levels were measured by radioimmunossay. Antiserum against alpha-MSH was found to affect the functional state of DA neurons, but only thorugh the intravenous route. Under physical stress i.v. injection of antiserum against alpha-MSH was accompanied by elevated levels of activity of the DA neurons of the substantia nigra. An intraventricular injection of the same antiserum was ineffective. In psychological stress, an effect was again seen only after intravenous injection of antiserum against alpha-MSH. In this situation, the activity in DA cell groups of the substantia nigra, ventral tegmental area and tubero-infundibular system was increased after antiserum injection. Possible influences from manipulations were checked; certain effects which depended upon experimental situation were noted. Our data suggest a modulatory influence of circulating alpha-MSH on the functional state of central DA systems.