Introduction: Childhood obesity has more than quadrupled in the last 30 years, with the prevalence in adolescents aged 12-17 years increasing from 5% in 1980 to 21% in 2012. The purpose of this study was to estimate the extent to which childhood obesity in Tennessee is associated with between-context differences (districts, schools and classes) and to identify factors at the district, school, class, and individual level that influence the individual weight status among 64,790 Tennessee children and adolescents. Methods: Crosssectional data from the Youth Risk Behavior Survey (YRBS) conducted in Tennessee (2010) were used to conduct multilevel analyses that account for the nesting of students in classes, classes in schools and schools in districts. The outcome variable was childhood obesity (>95th percentile). Explanatory variables included district-level factors (the proportion of children wearing seat belts or helmets in district and the proportion of being asked to show proof of age), school-level factors (current tobacco use in school, and HIV/AIDS education in school), class-level factors (the average of smoking days in past 30 days and the proportion of ever having exercised to lose weight in class) and individual-level factors (state geographical regions, age, gender, grade, ever ridden in a car driven by someone who had been drinking alcohol, ever carried a weapon, made a plan to kill yourself, ever used or early onset use of tobacco, alcohol, marijuana, exercised to control weight, school day television time, days of physical education (PE) classes. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were reported. Results: Multilevel analyses indicate that 0.90%, 0.08%, and 0.45% of the variation in obesity is associated with class, school and district differences, respectively. Male middle schoolers were at greater risk for obesity [OR: 1.82, C.I. (1.75, 1.89)] compared to females. For every one year increase in age, the relative odds of obesity increased by 11% (OR 0.89, 95% CI 0.88-0.91). Students with worse grades were more likely to have obesity [OR: 1.33, C.I. (1.13, 1.56)]. Students who watched TV 3 hours or more per day were more likely to be obese [OR: 1.31, C.I. (1.23, 1.40)] compared to those who did less than 3 hours per day. Similarly students who ever tried cigarettes were more likely to be obese [OR: 2.15, C.I. (1.62, 2.85)] compared to those students who did not. Students who reported wearing seat belts [OR: 0.05, C.I. (0.02, 0.16)] were less likely to be obese. Conclusions: This study highlights a number of modifiable factors on multiple levels associated with child and adolescent obesity in the state of Tennessee. The results emphasize the importance of targeting programs beyond individual adolescent factors to the child’s classes, schools, and school districts, to reduce the prevalence of obesity among Tennessee adolescents.

No description available.

La porphyrie aiguë intermittente (PAI) est la plus fréquente des porphyries hépatiques aiguës. Elle est décrite comme une maladie autosomique dominante dont le trait génétique est estimé à 1/1675 en France avec une pénétrance faible et variable allant de 10% à 50% dans les familles connues de PAI. La PAI est due à des mutations réduisant le niveau d’activité de l’hydroxyméthylbilane-synthase (HMBS). Son déficit entraîne l’accumulation de précurseurs neurotoxiques responsables de la symptomatologie clinique. Dans le foie, la synthèse d’hème est contrôlée par l’enzyme ALA-Synthétase 1 (ALAS1) dont l’activité est régulée par un rétrocontrôle négatif par le produit final : l’hème. Le traitement consiste à freiner l’induction d’ALAS1 induit par la carence en hème, par l’administration d’hème exogène. Ce traitement de la crise aiguë est très efficace mais génère rapidement une dépendance physique avec apparition de crises récurrentes nécessitant l’administration chronique d’hème exogène. L’objectif principal de ce projet a été d’étudier les mécanismes physiopathologiques et génétiques liés à cette pathologie afin de traiter et conseiller au mieux les patients. Une partie du projet a consisté à explorer les facteurs génétiques modulateurs de la pénétrance de la maladie. Tout d’abord, une prévalence minimale du trait génétique dans la population générale a été estimée à 1/1299 permettant d’en déduire une pénétrance de l’ordre de 1% alors que celle dans les familles PAI suivies par le CFP est estimée à 22,9 %. Ensuite, concernant les facteurs pouvant expliquer cette différence, la présence d’une mutation type non-sens est plus fréquemment associée aux formes sévères et à une pénétrance plus élevée. De plus, les études de corrélation et d’héritabilité suggèrent plutôt une transmission de type oligogénique associée à des facteurs épigénétiques modulateurs de la pénétrance dont le facteur environnemental. Une autre partie a consisté à explorer les effets de l’administration d’hème exogène sur les patients et un modèle murin de PAI créé génétiquement. Chez l’homme, le traitement est associé à une augmentation des formes chroniques (1,7 % avant vs 7,5 % après l’introduction du celui-ci). Dans le modèle murin de PAI, les injections intrapéritonéales répétées induisent une augmentation paradoxale d’ALAS1 (3 fois), une augmentation de l’hème oxygénase 1 qui catabolise l’hème (HMOX1, 9 fois) ainsi que des voies de l’inflammation (analyse transcriptomique et protéomique hépatique) et une surcharge en fer. De plus, cette administration induit une altération des complexes de la chaine respiratoire mitochondriale responsable d’anomalies du métabolisme énergétique au niveau hépatique, cérébral et musculaire pouvant expliquer la symptomatologie neuroviscérale. En conclusion, ce travail a permis d’explorer les caractéristiques génétiques de la maladie (prévalence, pénétrance) en remettant en cause le mode de transmission autosomique dominant jusqu’ici admis, et d’explorer les mécanismes physiopathologiques associées à l’administration d’hème exogène faisant de cette thérapeutique un pharmakon / The biosynthesis of porphyrins is one of the most conserved pathways known. By associating different metals, porphyrins give rise to the "pigments of life". The formation of haem is accomplished by a sequence of eight dedicated enzymes encoded by different genes, some being active in ubiquitous as well as in erythroid isoforms. In humans, the genes for each of the haem synthetic enzymes may become the target of mutations that give rise to an impaired cellular enzyme activity called porphyrias. The acute porphyrias are characterized by attacks of neuropsychiatric symptoms, which may be due to a toxic surplus of the porphyrin precursor 5-aminolevulinic acid, or a consequence of a deficit of vital hemoproteins. Mutations of the gene encoding the third enzyme: hydroxymethylbilane synthase, are associated with the most frequent type of acute hepatic porphyria, acute intermittent porphyria. AIP is thought to display autosomal dominant inheritance with incomplete penetrance. In the classical form of AIP, HMBS activity is about 50% lower than normal in all tissues. These levels of activity in basal conditions are not sufficiently low to cause symptoms. However, factors increasing hepatic heme demand, resulting in an upregulation of hepatic aminolevulinate synthase (ALAS1, the first enzyme of the heme biosynthesis pathway), precipitate acute attacks. The treatment of the attack of AIP consists to repress ALAS1 and restores metabolic equilibrium. But this treatment leads side effects and dependency. The pathophysiological mechanism of the disease is partially known and difficult to explore because there is not an AIP model or prediction model of porphyrogenicity. We aimed to obtain further insight into the pathophysiological mechanism of AIP and into the genetic (prevalence and penetrance) of AIP, and the contribution of genetic factors to the variable clinical expression of HMBS mutations.We first calculated the penetrance of HMBS mutations in AIP patients seen at the French reference center for porphyria: 22.9%. We then used the Exome Variant Server (EVS) to estimate the prevalence of deleterious HMBS mutations in the general population: 1/1299; and the penetrance of the AIP genetic trait in France: 1%. Finally, we investigated further the genetic factors underlying the penetrance of AIP by analyzing genotype/phenotype correlations, and the pattern of familial correlations for the symptoms of the acute crises of AIP. Intrafamily correlation studies showed correlations to be strong overall and modulated by kinship and the era in which the person was living, demonstrating strong influences of genetic and environmental modifiers on inheritance suggesting that AIP inheritance does not follow the classical autosomal dominant model. Null alleles were associated with a more severe phenotype and a higher penetrance than for other mutant alleles.On the other hand, we explored the effect of heme administration. In human, the introduction of hemin into the pharmacopeia has coincided with a 4.4-fold increase in the prevalence of chronic patients. We show that repeated hemin infusions in mice trigger a high level heme oxygenase 1 response, induce a pro-oxidative iron accumulation, a complex pattern of liver inflammation with macrophage infiltration and an alteration of oxidative phosphorylation

<p>Changes in swallowing function are common in elderly and chronically ill individuals. Therefore it is important to be aware of these changes and their prevalence. The aim of this study was to assess the prevalence of dysphagia in nursing homes in the municipality of Linköping, and to correlate dysphagia with variables that can be a cause or a consequence of dysphagia. These variables were gender, age, MMT-result, dentition, weight loss, medical diagnose or number of medications. The intention was also to examine the additional information regarding dysphagia supplied by pulse oximetry.</p><p>Sixty nursing home residents aged 74-101 years were chosen to participate in the study. The individual's ability to participate was based on their result on Mini-mental state and subjective judgements made by staff members and the authors. The material to assess oral motor and sensory function was the Nordic Orofacial Test - Screening. During the clinical swallowing examination the Standardised Swallowing Assessment (SSA) and pulse oximetry were used. In addition, data regarding the participants' medical diagnoses, number of medications and possible weight loss was collected.</p><p>The result showed that the prevalence of dysphagia and suspected dysphagia was 40 %. Oral dysphagia was present in 20 participants and pharyngeal dysphagia in seven participants. With pulse oximetry one participant with dysphagia and two with suspected dysphagia were identified in addition to those identified by SSA. Analysis of the assessed variables showed no correlations or any significant results.</p> / <p>Förändringar av sväljförmågan är vanligt hos äldre och kroniskt sjuka individer. Det är viktigt att vara medveten om dessa förändringar och hur vanligt förekommande det är med nedsatt sväljförmåga. Syftet med föreliggande studie var att undersöka förekomsten av dysfagi på äldreboenden i Linköpings kommun samt att korrelera dysfagi med parametrar som kan vara orsak till eller konsekvens av dysfagi. Dessa parametrar var kön, ålder, MMT-resultat, tandstatus, viktnedgång, sjukdomsdiagnos och antal läkemedel. Ett delsyfte i studien var att undersöka om man med hjälp av pulsoximetri kan upptäcka fler fall av dysfagi.</p><p>Sextio vårdtagare på äldreboenden, i åldern 74-101 år, valdes ut att delta i studien. Urvalet baserades på resultat på Mini-Mental Test samt personalens och testledarnas subjektiva bedömning om vårdtagarens möjlighet att delta. Materialet som användes för att bedöma oral motorik och sensorik var Nordiskt Orofacialt Test – Screening. Vid den kliniska sväljningsbedömningen användes Standardised Swallowing Assessment (SSA) och pulsoximetri. Utöver detta inhämtades uppgifter för samtliga deltagare om sjukdomsdiagnos, antal stående läkemedel samt eventuell viktnedgång.</p><p>Resultatet visade att förekomsten av dysfagi och misstänkt dysfagi var 40 %. Oral dysfagi förekom hos 20 deltagare och faryngeal dysfagi hos sju deltagare. Pulsoximetern identifierade en deltagare med dysfagi och två med misstänkt dysfagi utöver dem som identifierats med hjälp av SSA. Korrelations- och signifikansberäkningar av de undersökta parametrarna visade inga signifikanta resultat.</p>

<p>Social phobia is a disabling, lifelong disorder characterised by fear in social settings.</p><p>The aim of the present study was to gain more knowledge about diagnostic, neurobiologic and epidemiologic aspects of social phobia.</p><p>Thirty-two individuals were assessed by the Structured Clinical Interview for DSM-IV Axis I and II psychiatric disorders, the Karolinska Scales of Personality and the Temperament and Character Inventory. Social phobia was accompanied by concurrent axis I disorders in about 28% of individuals, lifetime axis I disorders in 54%, personality disorders in 60%, and avoidant personality disorder (APD) in 47%. This suggests that there is a high comorbidity between social phobia and APD according to the DSM-IV criteria. The personality profiles associated with social phobia were dominated by anxiety-related traits that were primarily related to social phobia itself and not to the presence of concurrent personality disorders.</p><p>Eighteen subjects with social phobia and eighteen controls were investigated with positron emission tomography and the radiolabeled serotonin precursor, [3 -11C]–5-HTP (5-HTP). Individuals with social phobia demonstrated proportionally lower regional relative whole brain accumulation of 5-HTP in areas of the frontal and temporal cortices as well as the striatum, but higher accumulation in the cerebellum. This suggests that there are imbalances in presynaptic serotonin function in individuals with social phobia, although this could only be confirmed in men, and not in women.</p><p>By means of a postal survey, distributed to 2000 randomly selected individuals, social phobia in Sweden was found to be common, with a point prevalence of 15.6%.</p>

<p>As evidenced by several trials, cognitive behavior therapy (CBT) is a highly effective treatment for Panic disorder with or without agoraphobia (PD). However, therapists are short in supply, and patients with agoraphobia may not seek therapy due to fear of leaving their homes or traveling certain distances. A major challenge therefore is to increase the accessibility and affordability of evidence-based psychological treatments.</p><p>This thesis is based on five studies; three treatment studies set up as randomized controlled trails (RCT), one prevalence study, and one study testing the equivalence of an Internet-administered diagnostic assessment tool with a clinician-administered interview.</p><p>Study I showed that the Swedish 12-month PD prevalence is consistent with findings in most other parts of the Western world (2.2%; CI 95% 1.0%-3.4%). There was a significant sex difference, with a greater prevalence for women (3.6%) compared to men (0.7%).</p><p>Study II showed that the validity of the computerized diagnostic interview (CIDI-SF) was generally low. However, the agoraphobia and obsessive-compulsive disorder modules had good specificity and sensitivity, respectively.</p><p>The three RCTs showed, directly or indirectly, that Internet-based self-help is superior to a waiting-list. When 10 individual weekly sessions of CBT for PD was compared with a 10-module self-help program on the Internet, the results suggest that Internet-administered self-help, plus minimal therapist contact via e-mail, is as effective as traditional individual CBT (80% vs. 67% no longer met criteria for panic disorder; composite within-group effect size was Cohen’s <i>d</i>= 0.78 vs. 0.99). One-year follow-up confirmed the results (92% vs. 88% no longer met criteria for panic disorder; <i>d</i>= 0.80 vs. 0.93). The results generally provide evidence to support the continued use and development of Internet-distributed self-help programs.</p>

<p>Social phobia is a disabling anxiety disorder characterized by an excessive fear of negative evaluation in social situations. The present thesis explored the epidemiology and neurobiology of the disorder. By means of a mailed questionnaire, the point prevalence of social phobia in the Swedish general population was estimated at 15.6%. However, prevalence rates varied between 1.9 and 20.4% across the different levels of distress and impairment used to define cases. Thus, although social anxiety is widespread within the community, the precise diagnostic boundaries for social phobia are difficult to determine. Social phobia was associated with female gender, low educational attainment, psychoactive medication use, and lack of social support. A cluster analysis revealed that subtypes of social phobia mainly differed dimensionally on a mild-moderate-severe continuum, with number of cases declining with increasing severity. Public speaking was the most common social fear in all groups of social phobics and in the population at large.</p><p>In the neurobiological studies, positron emission tomography was used to examine brain serotonin metabolism and changes in the regional cerebral blood flow (rCBF) response to public speaking stress following treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral group therapy. Social phobics exhibited lowered serotonin turnover, relative to non-phobics, mainly in the medial temporal cortex including the bilateral rhinal and periamygdaloid regions. Symptom improvement with cognitive-behavioral- as well as SSRI-treatment was accompanied by a reduced rCBF-response to public speaking in the amygdala, hippocampus and adjacent temporal cortex, i.e. regions that serve important functions in anxiety. Thorough suppression of rCBF in limbic brain regions was associated with favorable long-term treatment outcome. These results provide neuroimaging evidence for a presynaptic serotonergic dysfunction in social phobia and for a common neural mechanism whereby psychological and pharmacological anti-anxiety treatments act.</p>

<p>Reduced performance of the left ventricle to eject blood – left ventricular systolic dysfunction (LVSD) – is a common predecessor of the heart failure syndrome. With or without symptoms, LVSD is associated with a poor prognosis. However, with adequate treatment, the development or progression of symptoms, the need for hospitalisation and mortality can all be reduced. In the present work, the occurrence of LVSD was evaluated by echocardiography in a community-based sample of 75-year-old men and women (n = 433). LVSD was a common condition, with a prevalence rate of 6.8%. In nearly half the participants with LVSD, there was no clinical evidence of heart failure.</p><p>Community-based screening for asymptomatic LVSD has been proposed as a strategy to reduce the incidence of heart failure. Because of the high costs and low availability, echocardiography is not a suitable screening tool. The plasma concentration of B-type natriuretic peptide (BNP) has been the most advocated screening tool. Another alternative is the standard 12-lead electrocardiogram (ECG). Both the ECG and BNP were effective in excluding LVSD in our 75-year-old community-based sample. However, compared with BNP, the ECG had considerably better specificity. In screening for LVSD, BNP had a diagnostic value in addition to the ECG, but only in individuals with abnormal ECGs.</p><p>The left ventricular ejection fraction (LVEF) measured by echocardiography is a well-established index for describing left ventricular systolic function. The wall motion index (WMI) and the amplitude of mitral annulus motion (MAM) are suggested as alternative echocardiographic methods. Compared with MAM, the WMI had a more favourable agreement with the LVEF in our 75-year-old participants. Nonetheless, MAM was a strong predictor of mortality. MAM predicted the risk of all-cause and cardiac mortality independently of other risk factors. In addition, when it came to cardiac mortality, the predictive ability of MAM was independent of the LV function measured as the WMI.</p>

<p>This thesis is based on two independent studies, the first in Stockholm County (index year 1984; n=302), and the second, a replication and validation study, in Uppsala County (index year 1991; n=455).</p><p>The general aim was to study all individuals with Long-term Functional Psychosis (LFP) within the two counties of Sweden from an epidemiological perspective and to perform specific studies on a subgroup of individuals with schizophrenia. In the Stockholm study, the total one-year LFP prevalence was 5.3/1 000; in the the rural, suburban and urban areas it was 3.4, 5.6 and 6.6/1 000, respectively. The total one-year prevalence of LFP in Uppsala was 7.3/1 000; in the rural, peripheral city and central city areas it was 6.0, 7.0, and 8.7/1 000, respectively.</p><p>Within the non-schizophrenic subpopulation, a pronounced difference was demonstrated between the two studies with substantially higher prevalence rates in the Uppsala study. The schizophrenic subgroup in Uppsala was re-diagnosed using parallel diagnostic systems (DSM-III, DSM-III-R, DSM-IV and ICD-10), and reasonably comparable prevalence estimates were obtained.</p><p>In both studies antipsychotic drugs were most frequently prescribed for the patients with schizophrenia, and the doses were considered as low to moderate. In the Uppsala study the doses of antipsychotic drugs decreased with a longer duration of illness, while the opposite was found in the Stockholm study.</p><p>The increased mortality rate among patients with schizophrenia was mainly due to unnatural causes of death and cardiovascular diseases, particularly among males.</p><p>The main methodological differences between the two studies were in the sampling procedures. In the Uppsala study, a larger number of care facilities were screened, and a broader set of diagnostic criteria were used for identifying cases from different registers.</p>

Social phobia is a disabling anxiety disorder characterized by an excessive fear of negative evaluation in social situations. The present thesis explored the epidemiology and neurobiology of the disorder. By means of a mailed questionnaire, the point prevalence of social phobia in the Swedish general population was estimated at 15.6%. However, prevalence rates varied between 1.9 and 20.4% across the different levels of distress and impairment used to define cases. Thus, although social anxiety is widespread within the community, the precise diagnostic boundaries for social phobia are difficult to determine. Social phobia was associated with female gender, low educational attainment, psychoactive medication use, and lack of social support. A cluster analysis revealed that subtypes of social phobia mainly differed dimensionally on a mild-moderate-severe continuum, with number of cases declining with increasing severity. Public speaking was the most common social fear in all groups of social phobics and in the population at large. In the neurobiological studies, positron emission tomography was used to examine brain serotonin metabolism and changes in the regional cerebral blood flow (rCBF) response to public speaking stress following treatment with a selective serotonin reuptake inhibitor (SSRI) or cognitive-behavioral group therapy. Social phobics exhibited lowered serotonin turnover, relative to non-phobics, mainly in the medial temporal cortex including the bilateral rhinal and periamygdaloid regions. Symptom improvement with cognitive-behavioral- as well as SSRI-treatment was accompanied by a reduced rCBF-response to public speaking in the amygdala, hippocampus and adjacent temporal cortex, i.e. regions that serve important functions in anxiety. Thorough suppression of rCBF in limbic brain regions was associated with favorable long-term treatment outcome. These results provide neuroimaging evidence for a presynaptic serotonergic dysfunction in social phobia and for a common neural mechanism whereby psychological and pharmacological anti-anxiety treatments act.