Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.

BACKGROUND Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION NaHB is a highly effective and safe treatment that needs further controlled studies.

Cenesthopathy in adolescence: An appraisal of diagnostic overlaps along the anxiety–hypochondriasis–psychosis spectrum

Objective To discuss the diagnostic validity of unusual bodily perceptions along the spectrum from age-specific, often transitory and normal, to pathological phenomena in adolescence to hypochondriasis and finally to psychosis. Methods Critical literature review of the cornerstone diagnostic groups along the spectrum embracing anxiety and cenesthopathy in adolescence, hypochondriasis, and cenesthopathy and psychosis, followed by a discussion of the diagnostic overlaps along this spectrum. Results The review highlights significant overlaps between the diagnostic cornerstones. It is apparent that adolescents with unusual bodily perceptions may conceptually qualify for more than one diagnostic group along the spectrum. To determine whether cenesthopathies in adolescence mirror emerging psychosis, a number of issues need to be considered, i.e. age and mode of onset, gender, level of functioning and drug use. The role of overvalued ideas at the border between hypochondriasis and psychosis must be considered. Conclusion As unusual bodily symptoms may in some instances meet formal psychosis risk criteria, a narrow understanding of these symptoms may lead to both inappropriate application of the new DSM-5 attenuated psychosis syndrome and of treatment selection. On the other hand, the possibility of a psychotic dimension of unusual bodily symptoms in adolescents must always be considered as most severe expression of the cenesthopathy spectrum.

Career-choice readiness in adolescence: Developmental trajectories and individual differences

Developing career-choice readiness is an important task in adolescence, but current theory and research has provided a rather static view of the phenomenon. The present study investigated the development of career-choice readiness among a group of 325 Swiss students assessed four times every 5 months from seventh through eighth grade. A variable-centered approach applying latent curve modeling showed not only a linear increase of readiness over time but also significant inter-individual differences in the level and development of readiness. Higher levels were predicted by more self-esteem and generalized self-efficacy and fewer perceived barriers while increase in readiness was predicted by increase in occupational information. A person-centered approach applying latent class-growth analysis identified four distinct developmental trajectories: high-increasing (42%), high-decreasing (5%), moderate-increasing (42%), and constantly low (11%). Students with different trajectories showed significant differences in core self-evaluations, occupational knowledge, and barriers. The results suggest that environmental demands promote a developmental trend in readiness development that overrules individual differences for the majority of students. Individual differences affect the level of readiness to a greater extent than the process of its development. Career information seems pivotal for readiness increase.

Career adaptability development in adolescence: Multiple prdictors and effect on sense of power and life satisfaction

This longitudinal panel study investigated predictors of career adaptability development and its effect on development of sense of power and experience of life satisfaction among 330 Swiss eighth graders. A multivariate measure of career adaptability consisting of career choice readiness, planning, exploration, and confidence was applied. Based on Motivational Systems Theory four groups of predictors were assessed: positive emotional disposition, goal decidedness, capability beliefs and social context beliefs. Influence of gender, age, immigration background, parental educational level, and college-bound or vocational education plans were also assessed. Perceived social support and positive emotional disposition, non-immigration background, and continuing to vocational education were single significant predictors of more career adaptability development over the school year. Supporting the connection of career adaptability and positive youth development, increase in career adaptability over time predicted increase in sense of power and experience of life satisfaction.

Personality complexes in adolescence: Traits, interests, work values, and self-evaluations

Following the recent trend in psychology towards a more integrative view of personality, the study attempted to establish the connections and underlying complexes of fundamental personality dispositions within two cohorts of Swiss adolescents in eighth and eleventh grade (N = 492, ages 13 to 19): Big-Five basic traits, big six vocational interests, work values, and generalized self-efficacy and externality of control beliefs. Five factors were identified which accounted for 60% of variance among the relations of the variables: (1) enterprisingconventional interests, (2) favorable personality dispositions, (3) social-artistic personality characteristics, (4) investigative-realistic interests, and (5) work value endorsement. Crosssectional findings indicate that particularly agreeableness and conscientiousness become closer related to interests and work values with increasing grade-level.

General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

The Effects of Social Anxiety on the Development of Romantic Relationships in Adolescence

The present study sought to investigate the ways in which social anxiety impedes the development of romantic relationships across adolescence. Previous research has demonstrated a natural progression for romantic associations during adolescence in which teens transition from same- to mixed-sex peer groups, and finally to dyadic relationships with romantic partners (Connolly, Furman, Konarski, 2000; Dunphy, 1963). This model of development was the basis for the present investigation. Social anxiety was examined in terms of how it impacted affiliations at the same- and mixed sex peer group levels, and ultimately the formation of romantic relationships. This project involved administering a series of questionnaires and rating scales to students enrolled in the 9th through \2l grades. Participants included 457 adolescents (196 males, 261 females) recruited from public high schools in the state of Maine. The questionnaires assessed social anxiety, peer acceptance, heterosocial competence, gender composition of adolescent peer networks, dating history, and relationship quality with significant others in the adolescent's life. Higher levels of social anxiety were expected to be associated with impairment at each of these three levels. Given the proposed developmental progression, the effects of anxiety were theorized to be most pronounced within the older cohort of adolescents. Moreover, gender was expected to affect the pattern of results. Social anxiety is most prevalent among females (LaGreca, 1998; LaGreca & Lopez, 1998), who are also thought to progress along the proposed developmental trajectory more quickly than their male counterparts. Therefore, social anxiety was expected to impact the females to a greater degree at each of the three levels. Correlation coefficients, multivariate analyses of variance, and regression analyses were used to evaluate the data. Overall, despite some discrepant findings, the results supported the hypotheses. Social anxiety was affiliated with problems in the same-sex peer group, the mixed-sex clique, and, for older adolescents, romantic relationships. As expected, social anxiety affected females the most at each level. There seems to be a maladaptive pathway that socially anxious teens are following that is markedly different than their non-anxious counterparts.

The association between CD4+ lymphocyte count and measures of body composition in HIV-infected men

Purpose. This project was designed to describe the association between wasting and CD4 cell counts in HIV-infected men in order to better understand the role of wasting in progression of HIV infection.^ Methods. Baseline and prevalence data were collected from a cross-sectional survey of 278 HIV-infected men seen at the Houston Veterans Affairs Medical Center Special Medicine Clinic, from June 1, 1991 to January 1, 1994. A follow-up study was conducted among those at risk, to investigate the incidence of wasting and the association between wasting and low CD4 cell counts. Wasting was described by four methods. Z-scores for age-, sex-, and height-adjusted weight; sex-, and age-adjusted mid-arm muscle circumference (MAMC); and fat-free mass; and the ratio of extra-cellular mass (ECM) to body-cell mass (BCM) $>$ 1.20. FFM, ECM, and BCM were estimated from bioelectrical impedance analysis. MAMC was calculated from triceps skinfold and mid-arm circumference. The relationship between wasting and covariates was examined with logistic regression in the cross-sectional study, and with Poisson regression in the follow-up study. The association between death and wasting was examined with Cox's regression.^ Results. The prevalence of wasting ranged from 5% (weight and ECM:BCM) to almost 14% (MAMC and FFM) among the 278 men examined. The odds of wasting, associated with baseline CD4 cell count $<$200, was significant for each method but weight, and ranged from 4.6 to 12.7. Use of antiviral therapy was significantly protective of MAMC, FFM and ECM:BCM (OR $\approx$ 0.2), whereas the need for antibacterial therapy was a risk (OR 3.1, 95% CI 1.1-8.7). The average incidence of wasting ranged from 4 to 16 per 100 person-years among the approximately 145 men followed for 160 person-years. Low CD4 cell count seemed to increase the risk of wasting, but statistical significance was not reached. The effect of the small sample size on the power to detect a significant association should be considered. Wasting, by MAMC and FFM, was significantly associated with death, after adjusting for baseline serum albumin concentration and CD4 cell count.^ Conclusions. Wasting by MAMC and FFM were strongly associated with baseline CD4 cell counts in both the prevalence and incidence study and strong predictors of death. Of the two methods, MAMC is convenient, has available reference population data, may be the most appropriate for assessing the nutritional status of HIV-infected men. ^

(Table 1) Circulating levels of TT3 and TT4, and age, length, girth, and estimated body mass in polar bears (Ursus maritimus) from East Greenland 1999-2001

We investigated the multivariate relationships between adipose tissue residue levels of 48 individual organohalogen contaminants (OHCs) and circulating thyroid hormone (TH) levels in polar bears (Ursus maritimus) from East Greenland (1999-2001, n = 62), using projection to latent structure (PLS) regression for four groupings of polar bears; subadults (SubA), adult females with cubs (AdF_N), adult females without cubs (AdF_S) and adult males (AdM). In the resulting significant PLS models for SubA, AdF_N and AdF_S, some OHCs were especially important in explaining variations in circulating TH levels: polybrominated diphenylether (PBDE)-99, PBDE-100, PBDE-153, polychlorinated biphenyl (PCB)-52, PCB-118, cis-nonachlor, trans-nonachlor, trichlorobenzene (TCB) and pentachlorobenzene (QCB), and both negative and positive relationships with THs were found. In addition, the models revealed that DDTs had a positive influence on total 3,5,3'-triiodothyronine (TT3) in AdF_S, and that a group of 17 higher chlorinated ortho-PCBs had a positive influence on total 3,5,3',5'-tetraiodothyronine (thyroxine, TT4) in AdF_N. TH levels in AdM seemed less influenced by OHCs because of non-significant PLS models. TH levels were also influenced by biological factors such as age, sex, body size, lipid content of adipose tissue and sampling date. When controlling for biological variables, the major relationships from the PLS models for SubA, AdF_N and AdF_S were found significant in partial correlations. The most important OHCs that influenced TH levels in the significant PLS models may potentially act through similar mechanisms on the hypothalamic-pituitary-thyroid (HPT) axis, suggesting that both combined effects by dose and response addition and perhaps synergistic potentiation may be a possibility in these polar bears. Statistical associations are not evidence per se of biological cause-effect relationships. Still, the results of the present study indicate that OHCs may affect circulating TH levels in East Greenland polar bears, adding to the "weight of evidence" suggesting that OHCs might interfere with thyroid homeostasis in polar bears.

On the Use of Situational and Body Information in Goalkeeper Actions during a Soccer Penalty Kick

Artículo Experimental

Association of breakfast consumption with objectively measured and self-reported physical activity, sedentary time and physical fitness in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study

Objective: To examine the association of breakfast consumption with objectively measured and self-reported physical activity, sedentary time and physical fitness. Design: The HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Cross-Sectional Study. Breakfast consumption was assessed by two non-consecutive 24 h recalls and by a ‘Food Choices and Preferences’ questionnaire. Physical activity, sedentary time and physical fitness components (cardiorespiratory fitness, muscular fitness and speed/agility) were measured and self-reported. Socio-economic status was assessed by questionnaire. Setting: Ten European cities. Subjects: Adolescents (n 2148; aged 12?5–17?5 years). Results: Breakfast consumption was not associated with measured or self-reported physical activity. However, 24 h recall breakfast consumption was related to measured sedentary time in males and females; although results were not confirmed when using other methods to assess breakfast patterns or sedentary time. Breakfast consumption was not related to muscular fitness and speed/agility in males and females. However, male breakfast consumers had higher cardiorespiratory fitness compared with occasional breakfast consumers and breakfast skippers, while no differences were observed in females. Overall, results were consistent using different methods to assess breakfast consumption or cardiorespiratory fitness (all P#0?005). In addition, both male and female breakfast skippers (assessed by 24 h recall) were less likely to have high measured cardiorespiratory fitness compared with breakfast consumers (OR50?33; 95% CI 0?18, 0?59 and OR50?56; 95 %CI 0?32, 0?98,respectively). Results persisted across methods. Conclusions: Skipping breakfast does not seem to be related to physical activity,sedentary time or muscular fitness and speed/agility as physical fitness components in European adolescents; yet it is associated with both measured and self-reported cardiorespiratory fitness, which extends previous findings.

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment.

cut11+: A Gene Required for Cell Cycle-dependent Spindle Pole Body Anchoring in the Nuclear Envelope and Bipolar Spindle Formation in Schizosaccharomyces pombe

The “cut” mutants of Schizosaccharomyces pombe are defective in spindle formation and/or chromosome segregation, but they proceed through the cell cycle, resulting in lethality. Analysis of temperature-sensitive alleles of cut11+ suggests that this gene is required for the formation of a functional bipolar spindle. Defective spindle structure was revealed with fluorescent probes for tubulin and DNA. Three-dimensional reconstruction of mutant spindles by serial sectioning and electron microscopy showed that the spindle pole bodies (SPBs) either failed to complete normal duplication or were free floating in the nucleoplasm. Localization of Cut11p tagged with the green fluorescent protein showed punctate nuclear envelope staining throughout the cell cycle and SPBs staining from early prophase to mid anaphase. This SPB localization correlates with the time in the cell cycle when SPBs are inserted into the nuclear envelope. Immunoelectron microscopy confirmed the localization of Cut11p to mitotic SPBs and nuclear pore complexes. Cloning and sequencing showed that cut11+ encodes a novel protein with seven putative membrane-spanning domains and homology to the Saccharomyces cerevisiae gene NDC1. These data suggest that Cut11p associates with nuclear pore complexes and mitotic SPBs as an anchor in the nuclear envelope; this role is essential for mitosis.