A model for physical activity, bahaviour and energy expenditure assessment in real-life condition

RésuméL'origine de l'obésité, qui atteint des proportions épidémiques, est complexe. Elle est liée au mode de vie et au comportement des individus par rapport à l'activité physique, expression des choix individuels et de l'interaction avec l'environnement. Les mesures du comportement au niveau de l'activité physique des individus face à leur environnement, la répartition des types d'activité physique, la durée, la fréquence, l'intensité, et la dépense énergétique sont d'une grande importance. Aujourd'hui, il y a un manque de méthodes permettant une évaluation précise et objective de l'activité physique et du comportement des individus. Afin de compléter les recherches relatives à l'activité physique, à l'obésité et à certaines maladies, le premier objectif du travail de thèse était de développer un modèle pour l'identification objective des types d'activité physique dans des conditions de vie réelles et l'estimation de la dépense énergétique basée sur une combinaison de 2 accéléromètres et 1 GPS. Le modèle prend en compte qu'une activité donnée peut être accomplie de différentes façons dans la vie réelle. Les activités quotidiennes ont pu être classées en 8 catégories, de sédentaires à actives, avec une précision de 1 min. La dépense énergétique a pu peut être prédite avec précision par le modèle. Après validation du modèle, le comportement des individus de l'activité physique a été évalué dans une seconde étude. Nous avons émis l'hypothèse que, dans un environnement caractérisé par les pentes, les personnes obèses sont tentées d'éviter les pentes raides et de diminuer la vitesse de marche au cours d'une activité physique spontanée, ainsi que pendant les exercices prescrits et structurés. Nous avons donc caractérisé, par moyen du modèle développé, le comportement des individus obèses dans un environnement vallonné urbain. La façon dont on aborde un environnement valloné dans les déplacements quotidiens devrait également être considérée lors de la prescription de marche supplémentaire afin d'augmenter l'activité physique.SummaryOrigin of obesity, that reached epidemic proportion, is complex and may be linked to different lifestyle and physical activity behaviour. Measurement of physical activity behaviour of individuals towards their environment, the distribution of physical activity in terms of physical activity type, volume, duration, frequency, intensity, and energy expenditure is of great importance. Nowadays, there is a lack of methods for accurate and objective assessment of physical activity and of individuals' physical activity behaviour. In order to complement the research relating physical activity to obesity and related diseases, the first aim of the thesis work was to develop a model for objective identification of physical activity types in real-life condition and energy expenditure based on a combination of 2 accelerometers and 1 GPS device. The model takes into account that a given activity can be achieved in many different ways in real life condition. Daily activities could be classified in 8 categories, as sedentary to active physical activity, within 1 min accuracy, and physical activity patterns determined. The energy expenditure could be predicted accurately with an accuracy below 10%. Furthermore, individuals' physical activity behaviour is expression of individual choices and their interaction with the neighbourhood environment. In a second study, we hypothesized that, in an environment characterized by inclines, obese individuals are tempted to avoid steep positive slopes and to decrease walking speed during spontaneous outdoor physical activity, as well as during prescribed structured bouts of exercise. Finally, we characterized, by mean of the developed model, the physical activity behaviour of obese individuals in a hilly urban environment. Quantifying how one tackles hilly environment or avoids slope in their everyday displacements should be also considered while prescribing extra walking in free-living conditions in order to increase physical activity.

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is an inherited form of retinal degeneration that leads to progressive visual-field constriction and blindness. Although the disease manifests only in the retina, mutations in ubiquitously expressed genes associated with the tri-snRNP complex of the spliceosome have been identified in patients with dominantly inherited RP. We screened for mutations in PRPF6 (NM_012469.3), a gene on chromosome 20q13.33 encoding an essential protein for tri-snRNP assembly and stability, in 188 unrelated patients with autosomal-dominant RP and identified a missense mutation, c.2185C>T (p.Arg729Trp). This change affected a residue that is conserved from humans to yeast and cosegregated with the disease in the family in which it was identified. Lymphoblasts derived from patients with this mutation showed abnormal localization of endogenous PRPF6 within the nucleus. Specifically, this protein accumulated in the Cajal bodies, indicating a possible impairment in the tri-snRNP assembly or recycling. Expression of GFP-tagged PRPF6 in HeLa cells showed that this phenomenon depended exclusively on the mutated form of the protein. Furthermore, analysis of endogenous transcripts in cells from patients revealed intron retention for pre-mRNA bearing specific splicing signals, according to the same pattern displayed by lymphoblasts with mutations in other PRPF genes. Our results identify PRPF6 as the sixth gene involved in pre-mRNA splicing and dominant RP, corroborating the hypothesis that deficiencies in the spliceosome play an important role in the molecular pathology of this disease.

The European Board of Physical and Rehabilitation Medicine : the past, the present and the future [Europejska Rada Medycyny Fizykalnej i Rehabilitacji: przeszłość, teraźniejszość i perspektywy]

Right from the beginning of the development of the medical specialty of Physical and Rehabilitation Medicine (PRM) the harmonization of the fields of competence and the specialist training across Europe was always an important issue. The initially informal European collaboration was formalized in 1963 under the umbrella of the European Federation of PRM. The European Academy of PRM and the UEMS section of PRM started to contribute in 1969 and 1974 respectively. In 1991 the European Board of Physical and Rehabilitation Medicine (EBPRM) was founded with the specific task of harmonizing education and training in PRM in Europe. The EBPRM has progressively defined curricula for the teaching of medical students and for the postgraduate education and training of PRM specialists. It also created a harmonized European certification system for medical PRM specialists, PRM trainers and PRM training sites. European teaching initiatives for PRM trainees (European PRM Schools) were promoted and learning material for PRM trainees and PRM specialists (e-learning, books and e-books, etc.) was created. For the future the Board will have to ensure that a minimal specific undergraduate curriculum on PRM based on a detailed European catalogue of learning objectives will be taught in all medical schools in Europe as a basis for the general medical practice. To stimulate the harmonization of national curricula, the existing postgraduate curriculum will be expanded by a syllabus of competencies related to PRM and a catalogue of learning objectives to be reached by all European PRM trainees. The integration of the certifying examination of the PRM Board into the national assessment procedures for PRM specialists will also have to be promoted.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents.

CONTEXT: Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children. OBJECTIVE: To examine the independent and combined associations between objectively measured time in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time with cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from 14 studies between 1998 and 2009 comprising 20 871 children (aged 4-18 years) from the International Children's Accelerometry Database. Time spent in MVPA and sedentary time were measured using accelerometry after reanalyzing raw data. The independent associations between time in MVPA and sedentary time, with outcomes, were examined using meta-analysis. Participants were stratified by tertiles of MVPA and sedentary time. MAIN OUTCOME MEASURES: Waist circumference, systolic blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and insulin. RESULTS: Times (mean [SD] min/d) accumulated by children in MVPA and being sedentary were 30 (21) and 354 (96), respectively. Time in MVPA was significantly associated with all cardiometabolic outcomes independent of sex, age, monitor wear time, time spent sedentary, and waist circumference (when not the outcome). Sedentary time was not associated with any outcome independent of time in MVPA. In the combined analyses, higher levels of MVPA were associated with better cardiometabolic risk factors across tertiles of sedentary time. The differences in outcomes between higher and lower MVPA were greater with lower sedentary time. Mean differences in waist circumference between the bottom and top tertiles of MVPA were 5.6 cm (95% CI, 4.8-6.4 cm) for high sedentary time and 3.6 cm (95% CI, 2.8-4.3 cm) for low sedentary time. Mean differences in systolic blood pressure for high and low sedentary time were 0.7 mm Hg (95% CI, -0.07 to 1.6) and 2.5 mm Hg (95% CI, 1.7-3.3), and for high-density lipoprotein cholesterol, differences were -2.6 mg/dL (95% CI, -1.4 to -3.9) and -4.5 mg/dL (95% CI, -3.3 to -5.6), respectively. Geometric mean differences for insulin and triglycerides showed similar variation. Those in the top tertile of MVPA accumulated more than 35 minutes per day in this intensity level compared with fewer than 18 minutes per day for those in the bottom tertile. In prospective analyses (N = 6413 at 2.1 years' follow-up), MVPA and sedentary time were not associated with waist circumference at follow-up, but a higher waist circumference at baseline was associated with higher amounts of sedentary time at follow-up. CONCLUSION: Higher MVPA time by children and adolescents was associated with better cardiometabolic risk factors regardless of the amount of sedentary time.

Effects of recommended levels of physical activity on pregnancy outcomes.

OBJECTIVE: We sought to examine the relation between recommended levels of physical activity during pregnancy and pregnancy outcomes. STUDY DESIGN: We conducted an observational study with energy expenditure, aerobic fitness, and sleeping heart rate measured in 44 healthy women in late pregnancy. Medical records were examined for pregnancy outcome. RESULTS: Active women, who engaged in > or = 30 minutes of moderate physical activity per day, had significantly better fitness and lower sleeping heart rate compared to the inactive. Duration of second stage of labor was 88 and 146 minutes in the active vs inactive women, respectively (P = .05). Crude odds ratio of operative delivery in the inactive vs the active was 3.7 (95% confidence interval, 0.87-16.08). Birthweight, maternal weight gain, and parity adjusted odds ratio was 7.6 (95% confidence interval, 1.23-45.8). Neonatal condition and other obstetric outcomes were similar between groups. CONCLUSION: Active women have better aerobic fitness as compared to inactive women. The risk for operative delivery is lower in active women compared to inactive, when controlled for birthweight, maternal weight gain, and parity. Further studies with larger sample size are required to confirm the association between physical activity and pregnancy outcomes.

Physical activity is inversely associated with high blood pressure independently of overweight in Brazilian adolescents.

The purpose of this study was to assess the relationship between blood pressure (BP) levels and physical activity (PA) domains accounting for overweight/obesity. Adolescents aged 10 to 17 years old were recruited (n = 1021). International Obesity Task Force (IOTF) criteria were used to define overweight and obesity. High BP was defined using the Center of Disease Control and Prevention criteria. Different domains of PA (school activities, sport out of school, and leisure time PA) were assessed using a validated questionnaire. The prevalence of overweight/obesity was 21.9% for boys and 14.8% for girls. Some 13.4% of boys and 10.2% of girls, respectively, had high blood pressure (HBP). A strong and positive association was found between overweight and HBP. After adjustment for body mass index (BMI), total PA was inversely associated with BP. When all PA domains were entered simultaneously in a regression model, and after adjustment for BMI, only sport out of school was significantly and inversely associated with systolic BP [β: -0.82 (-1.50; -0.13)]. These findings open avenue for the early prevention of HBP by the prevention of obesity and promotion of PA.

One- and two-center physical space partitioning of the energy in the density functional theory

A conceptually new approach is introduced for the decomposition of the molecular energy calculated at the density functional theory level of theory into sum of one- and two-atomic energy components, and is realized in the "fuzzy atoms" framework. (Fuzzy atoms mean that the three-dimensional physical space is divided into atomic regions having no sharp boundaries but exhibiting a continuous transition from one to another.) The new scheme uses the new concept of "bond order density" to calculate the diatomic exchange energy components and gives them unexpectedly close to the values calculated by the exact (Hartree-Fock) exchange for the same Kohn-Sham orbitals

High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function.

High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at ≥22 mg/liter (P = 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.