Synaptic communication mediates the assembly of a self-organizing circuit that controls reproduction.

Migration of gonadotropin-releasing hormone (GnRH) neurons from their birthplace in the nasal placode to their hypothalamic destination is critical for vertebrate reproduction and species persistence. While their migration mode as individual GnRH neurons has been extensively studied, the role of GnRH-GnRH cell communication during migration remains largely unexplored. Here, we show in awake zebrafish larvae that migrating GnRH neurons pause at the nasal-forebrain junction and form clusters that act as interhemisphere neuronal ensembles. Within the ensembles, GnRH neurons create an isolated, spontaneously active circuit that is internally wired through monosynaptic glutamatergic synapses into which newborn GnRH neurons integrate before entering the brain. This initial phase of integration drives a phenotypic switch, which is essential for GnRH neurons to properly migrate toward their hypothalamic destination. Together, these experiments reveal a critical step for reproduction, which depends on synaptic communication between migrating GnRH neurons.

Fifteen years of the Family Eating and Activity Habits Questionnaire (FEAHQ): an update and review.

BACKGROUND: The Family Eating and Activity Habits Questionnaire (FEAHQ) is a 32-item self-report instrument designed to assess the eating and activity habits of family members as well as obesogenic factors in the overall home environment (stimulus and behaviour patterns) related to weight. Originally, this questionnaire, which was developed in Israel, was designed for use in family-based weight-management interventions that emphasized changes in the environment, and in parents' knowledge, behaviours and modelling. It was developed for use with children aged 6-11 years and designed for co-completion by parents or caretakers and their children. Over the years, it has been administered in research and clinical settings in Israel, England, Australia and other countries. Its 15-year anniversary calls for an update in the literature regarding adjustments made to improve its use in different settings and with different ethnic populations and the psychometric properties of the revised version. OBJECTIVE: The goal of this paper is threefold: (i) to describe the history and development of the FEAHQ; (ii) to present new data supporting the psychometric properties of the subscales of the Revised FEAHQ (FEAHQ-R) for ages 6-12 years and (iii) to review the clinical and research literature reporting on FEAHQ subscales. METHODS: The psychometric properties of the revised questionnaire were evaluated in a randomized control trial and in a naturalistic, community-based study to promote healthy lifestyle among families with children 6-12 years of age from different ethnic populations. RESULTS: The tool demonstrated good test-retest reliability when completed by caretakers and very good internal consistency. The questionnaire scores discriminated between obese and normal-weight children and predicted the weight classification of 66% of the participants. CONCLUSIONS: The FEAHQ-R is a useful clinical tool for identifying target behaviors for treatment and monitoring treatment progress that centers on overweight prevention and weight management.

Mitochondrial VDAC1: function in cell life and death and a target for cancer therapy.

Found at the outer mitochondrial membrane, the voltage-dependent anion channel, VDAC, assumes a crucial position in the cell, serving as the main interface between mitochondrial and cellular metabolisms by mediating transport of ions and metabolites. VDAC thus functions as a gatekeeper, controlling cross-talk between mitochondria and the rest of the cell. Moreover, its location at the boundary between the mitochondria and the cytosol enables VDAC to interact with proteins that mediate and regulate the integration of mitochondrial functions with other cellular activities. Here, we review current knowledge related to the roles played by VDAC in the regulation of cell life and cell death, with relation to cancer. The current concepts of altered metabolism in cancer cells are presented with specific emphasis on mitochondrial, more specifically VDAC1-bound hexokinase (HK), facilitating and promoting the high glycolytic tumor phenotype. In this respect, the up-regulation of HK expression in tumor cells and its binding to VDAC provide both a metabolic benefit and apoptosis-suppressive capacity that offers the cell a growth advantage and increases its resistance to chemotherapy. VDAC has also been recognized as a key protein in mitochondria-mediated apoptosis since it is the proposed target for the pro- and antiapoptotic Bcl-2-family of proteins, as well as due to its function in the release of apoptotic proteins located in the inter-membranal space. These and other functions point to VDAC1 as being a rational target for the development of a new generation of therapeutics.

Impaired migration signaling in the hippocampus following prenatal hypoxia.

Prenatal hypoxia ischemia is a major cause of neurodevelopmental impairment in the newborn, associated with risk for motor, behavioral and cognitive impaired outcomes. We used an established mouse model of maternal hypoxia to examine the immediate molecular responses of signaling pathways associated with both cell death and neurogenesis. We also characterized responses to maternal pre-treatment with MgSO(4). Maternal hypoxia at embryonic day 17 (E17) failed to trigger inflammation or cell death in fetal brain at 24 h after hypoxia. However, maternal hypoxia decreased levels of neuronal migration signaling: Reelin (53% of control), Disabled 1 (Dab1, 77% of control), and amyloid precursor protein (APP, 64% of control) 2 h after the insult. These changes persisted for 24 h. At later times, Reelin levels in hippocampi of newborns in the maternal hypoxia-treated group increased compared to controls. Full protection from maternal hypoxia effects on hippocampal Reelin levels resulted from maternal pre-treatment with MgSO(4). Hypoxia and MgSO(4) increased radial and lateral migration distance in the CA1 four days after the insult, while in the DG the hypoxia treatment alone increased migration. Maternal hypoxia and MgSO(4) pre-treatment also stimulated hippocampal expression of genes related to neurogenesis, such as BDNF and NeuroD4. Taken together, the long-term neurodevelopmental outcome of prenatal and perinatal hypoxia may depend on perturbation of developmental signals that affect neuronal migration.

Protective self-presentation style: association with disordered eating and anorexia nervosa mediated by sociocultural attitudes towards appearance.

OBJECTIVE: We tested the hypothesis that a protective self-presentation style (Lennox and Wolfe, 1984) is associated with eating pathology and anorexia nervosa (AN) and that this association is mediated by sociocultural attitudes towards appearance emphasizing the thin ideal. METHOD: We compared the protective-presentation style of women with AN (N=17), partially recovered women (N=110), fully recovered women (N=73), and female controls (N=374). RESULTS: Ill women had a more protective self-presentation style than partially or fully recovered women, who in turn had a more protective self-presentation style than controls. Sociocultural attitudes towards appearance fully mediated the association between protective self-presentation and disordered eating. CONCLUSIONS: Protective self-presentation may therefore be a risk factor for AN and/or a prognostic factor. Implications for therapy and prevention are discussed.

A comparison between desert and Mediterranean antlion populations: differences in life history and morphology.

We performed a transplant experiment to compare the life histories and morphologies of five geographically representative antlion Myrmeleon hyalinus populations along a sharp climatic gradient, from a Mediterranean climate in Israel's north to a desert climate in the south. Larvae were raised in two environmental chambers simulating Mediterranean and desert climates to investigate the extent to which the different populations exhibit phenotypic plasticity. Along the north-to-south climatic gradient, we observed a gradient in body mass prior to pupation and in pupation rate. Mediterranean populations suffered higher mortality rate when exposed to desert conditions, whereas the mortality rate of desert populations was consistent between Mediterranean and desert conditions. Our results regarding body mass, pupation rate and mortality rate suggest that Mediterranean populations had a more flexible response compared with desert populations. An analysis of digital photographs was used to measure population morphological differences, which were usually indicative of a decrease in trait size along the north-to-south gradient. We show how climatic gradients translate into phenotypic differences in an antlion population and provide a morphometric tool to distinguish between instar stages.

Early-onset Alzheimer's disease with a de novo mutation in the presenilin 1 gene.

A 32-year-old woman diagnosed with very rapidly progressing early-onset Alzheimer's disease (EOAD), age of onset 29 years, and S170F mutation in presenilin 1 gene (PSEN1) is presented. Neuroimaging conducted 2 years after the first symptoms was typical for the advanced stage of Alzheimer's disease (AD), showing cortical brain atrophy, particularly within hippocampus, frontal and temporal cortex. The unaffected parents of the proband are not carriers of the mutation. The paternity was confirmed by microsatellite typing, strongly suggesting de novo origin of S170F mutation. In silico modeling of S170F mutation impact on presenilin 1 (PS1) transmembrane structure indicates that the mutation considerably alters putative interactions of PS1 with other proteins within gamma-secretase complex.

[Criteria for hospitalization of adolescents with anorexia nervosa according to postmodernistic approach].

The increased incidence of eating disorders in the Western world raises the demand for discussion regarding recommendations for hospitalization of adolescents with these disorders. The American Psychiatric Association has established criteria for hospitalization that include physiological, psychological and social components. The societal and professional discussion regarding adolescent hospitalization is frequently based on obvious assumptions and accepted discourses, such as the hierarchical pattern in the medical model, the control perception, knowledge ownership, freedom of choice, etc. These issues challenge the discussion on the hospitalization of adolescents with eating disorders. Eating disorders involve dimensions of control, boundaries, and psychological space, which are the essence of the difference between therapy in hospital or in the community. Personality and personal patterns, as well as associated psychopathology, family structure and other factors influence these dimensions and the ability of teenagers to be helped by the professional frameworks approached by them. This manuscript raises questions in relation to issues regarding hospitalization based on conflicts unique to eating disorders.

The -22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer's disease in Poland.

The -22c/t polymorphism in the promoter of the presenilin 1 gene is associated with increased risk for Alzheimer's disease (AD) in some populations. It was shown that -22c allele is connected with two-fold decrease in promoter activity. We studied the impact of the polymorphism in groups of Polish late-onset and early-onset AD patients. Our results suggest that -22c/t polymorphism is not connected with AD in Polish population. The -22t allele showed a high degree of linkage disequilibrium with -2797 insertion of 13 bp. An additional -2923g/t polymorphism is also not connected with -22c/t and is not a risk factor for AD.

[Clinical mentorship as a bridge to life in the treatment of eating disorders].

The aim of this article is to describe a community-based multi-modality intensive treatment program, which demonstrates a significant reduction in symptoms of eating disorders while providing an opportunity to deal with the functional and social skills. Treatment is delivered through a multidisciplinary team. The uniqueness of the team is in the inclusion of clinical mentors. These are social workers, art therapists and graduate level psychology students who are trained to connect with clients in an informal, intensive manner (10-40 hours a week). The mentors focus on legitimizing healthy attitudes to food, eating and life, while highlighting the pain and loss associated with the disorder. The mentors serve as meal companion and calming figure, representing the healthy self-caring voice. The relationship established during the many hours spent together becomes a powerful experience, completely different from the isolation of the disorder. The treatment intervenes in most areas of life, focusing on an active search for possibilities, in contrast to the emptiness associated with the disorder. This article presents the results and principles of a 2.5-year practice. Seventeen patients, ill for 6 years and more, completed this program more than a year ago. An assessment of their BMI and their general outcome using Eckert scales was performed. One year after completing the program, 76% of the patients were defined as recovered and 12% were almost recovered with only a few remaining symptoms. All of these patients function satisfactorily in the community, both in social and occupational aspects. Six percent were partially recovered and 6% suffered from regression during the first year of follow-up. This treatment provides the intensity required in hospitalizations, while enabling patients to stay in the community and maintain those activities that survive the disorder. This program has proven to work well with chronic patients. Further data, not analyzed as yet, also indicates the efficacy of this treatment in acute cases.

Familial approach to the treatment of childhood obesity: conceptual mode.

This model for the management of childhood obesity uses a family-based approach. Change is delivered through the parents (instead of the obese child) emphasizing a healthy lifestyle and not weight reduction as in previously published, family-based management of childhood obesity. This intervention integrates behavioral, social learning, and family system approaches. The proposed approach includes changes in parental cognition, emphasizing "parenthood presence"; parents serve both as a source of authority and a role model for the obese child, providing a family environment that fosters healthy practices related to weight control issues and de-emphasizing personal responsibility for control of health behavior.

Impact of treatment for childhood obesity on parental risk factors for cardiovascular disease.

BACKGROUND: Family-based approaches using the parents as agents of change to treat childhood obesity are superior to programs targeting only children in achieving weight reduction and have a lower dropout rate. OBJECTIVE: The aim of this study was to compare the impact of two behavioral approaches (parents only vs children only) for the treatment of childhood obesity on parental weight, eating, and activity habits as well as cardiovascular risk factors. DESIGN: A randomized 1-year clinical intervention study was performed. METHODS: Sixty obese children (>/=20% over ideal weight for age, height, and sex), ages 6-11 years, were randomly allocated to the experimental (parents as sole agents of change) or conventional groups (children as sole agents of change). Fourteen (1-h-long) support/educational sessions were conducted by a clinical dietitian for the parents in the experimental group and 30 sessions for children in the conventional group. Anthropometric and biochemical measurements were determined at the start and end of the program. RESULTS: The experimental approach, when compared to the conventional intervention, was found to be superior in the reduction of fathers overweight (P < 0.05). The former approach resulted also in improved profile of risk factors for cardiovascular disease in both parents. These changes could be ascribed to a greater improvement in eating and activity behaviors observed in parents belonging to the experimental intervention group who participated in a family-based intervention to treat their children's obesity. CONCLUSIONS: Treatment of childhood obesity targeting the parents as the sole agent of change, which is more effective for the treatment of childhood obesity when compared to a children-oriented program, may in addition award parents with the benefit of changing their own eating and activity patterns, thus making this program ideal for treatment of obesity in children and their overweight parents.

Reliability and validity of the Family Eating and Activity Habits Questionnaire.

OBJECTIVE: The purpose of this work was to develop and test an instrument that will identify the factors that facilitate childhood obesity and monitor the environmental changes and family behavior modifications associated with weight loss. DESIGN AND METHODS: The relevant factors that affect obesity and weight loss in children were divided into four scales: activity level, stimulus exposure, eating related to hunger, and eating style. We designed a questionnaire to be completed by the parents of the obese child aged 6-11 years. Scores accumulated were calculated separately for each member of the family. Higher numerical scores reflected less appropriate eating patterns. The questionnaire reliability (test-retest), internal consistency and ability to discriminate obese vs normal-weight children's behaviors was tested using a pilot population of 40 mothers not enrolled in a formal weight loss program. The questionnaire reliability (parents' report and spouse report) and predictive validity was tested using a selective population: 60 parents of obese children enrolled in a clinical intervention intended to treat childhood obesity with an environmental approach vs a dietary approach. RESULTS: The content validity of the questionnaire was evaluated by a team of ten experts. Cronbach's alpha was calculated to test internal consistency. Mean r was 0.83. Pearson's correlation coefficients were computed between test and retest scores for individual items and for the total score, and ranged from 0.78 to 0.90 (median 0.84) (P < 0.01 for all). Total score test-retest r was 0.85 (P < 0.01). The total family score was also higher in the families with an obese child compared to families with a normal-weight child, P < 0.01. No significant differences were noted between parent report and spouse report scores. The construct validity of the questionnaire was also supported by its high sensitivity to weight loss treatment. Weight loss in the child correlated highly with improvement in questionnaire score. CONCLUSIONS: The Family Activity and Eating Habits Questionnaire is reliable and internally consistent, and it is useful as an optional tool for planning an intervention program for childhood obesity.

Parents as the exclusive agents of change in the treatment of childhood obesity.

BACKGROUND: Excessive weight in childhood is a serious public health concern because of its costly health consequences and its increasing prevalence. OBJECTIVE: Our objective was to compare the efficacy of a family-based approach for the treatment of childhood obesity, in which the parents served as the exclusive agents of change, with that of the conventional approach, in which the children served as the agents of change. DESIGN: This study had a randomized, longitudinal prospective design and lasted 1 y. Sixty obese children aged 6-11 y were randomly allocated to the experimental (parents as agents of change) or control (children as agents of change) group. Anthropometric and biochemical measurements were determined at the start and end of the study. A sociodemographic questionnaire and a family eating and activity habits questionnaire were completed by both parents. Hour-long support and educational sessions were conducted by a clinical dietitian: 14 sessions for the parents in the experimental group and 30 sessions for the children in the control group. RESULTS: The dropout rate was nine times greater in the control group (n = 9) than in the experimental group (n = 1). Mean percentile weight reduction was significantly (P < 0.03) higher in children in the experimental group (14.6%) than in the control group (8.1%). CONCLUSIONS: Treatment of childhood obesity with parents as the exclusive agents of change was superior to the conventional approach, as indicated by the dropout rate and the percentage weight loss of the children during the 1-y intervention.

Role of behaviour modification in the treatment of childhood obesity with the parents as the exclusive agents of change.

OBJECTIVE: This study examined the reduction in overweight and changes in eating-related behaviours in obese children treated with a family-based approach, in which the parents were the exclusive agents of change. Results were compared to the conventional approach in which children are responsible for their own weight loss. DESIGN: A one-year longitudinal prospective design was used. Participants were randomly allocated for the experimental (parents as the agents of change) or the conventional (children as the agents of change) intervention. METHODS: Sixty obese children (20% over ideal weight for age, height and gender) aged 6-11 y (mean+/-s.d. 9.2+/-1.0 y) were included in the study. Anthropometric measurements and biochemical tests were performed on the children and their parents before and after the programme, and both parents completed a sociodemographic and a family eating and activity habits questionnaire. Hour-long support/educational sessions were conducted by a clinical dietitian-14 sessions for the parents in the experimental intervention and 30 for the children in the conventional intervention. Individual sessions were held for members of both groups, when necessary. RESULTS: Significant differences were found between the two groups in the reduction of exposure to food stimuli and changes in eating habits (eating while standing, watching TV, reading or doing homework, eating following stress and eating between meals). Mean weight reduction (by percentile) was significantly greater in the experimental intervention group (parent-only treatment) in comparison to the conventional intervention group (child-only treatment). CONCLUSIONS: Treatment of childhood obesity with the parents as the exclusive agents of change, induces more behavioural changes as well as greater weight loss, than the conventional approach.

[Angina pectoris as a symptom of gastric volvulus].

Angina pectoris is a common complaint in any emergency service, but it rarely is of extracardiac origin. A rare case of gastric volvulus which presented a recurrent angina pectoris in a 47-year-old man is reported. Repeated episodes of angina pectoris in a patient with a negative cardiac investigation should alert the physician to the possibility of extracardiac pathology.

Synergism between infarct-borne left ventricular dysfunction and cardiomegaly in increasing the risk of coronary bypass surgery.

The effect of cardiomegaly on operative and late mortality in patients with left ventricular dysfunction undergoing coronary bypass operation was investigated. The study group consisted of 178 patients whose left ventricular ejection fraction was below 45% and who were operated on from 1978 through 1985. Forty-five patients (group A) had severe left ventricular dysfunction (ejection fraction < 30%) and 133 (group B) had moderate dysfunction (30% > ejection fraction > 45%). Twenty-four of group A (53%) and 54 of group B (41%) patients had cardiomegaly (cardiothoracic ratio on chest x-ray films > 0.5). There were 10 (6%) hospital deaths, four in group A (9%) and six in group B (4.5%). All four deaths in group A and the six deaths in group B were patients who had cardiomegaly. Regardless of the severity of the left ventricular dysfunction, there was no operative death among patients with normal heart size (p < 0.001). Age over 65, bypass time longer than 2 hours, and incomplete revascularization emerged as risk factors. Follow-up ranged from 5 to 13 years (mean 7.8 years). Overall 5-year actuarial survival, including hospital mortality, was 80% +/- 3%. Reduced 5-year survival was observed in patients with cardiomegaly (67% +/- 5% versus 91% +/- 3%, p < 0.05). Five- and 10-year survival of patients from group A with cardiomegaly was 53% +/- 7% and 18% +/- 13%, respectively.

Solid swallowing versus water swallowing: manometric study of dysphagia.

The aim of the study was to investigate whether a soft solid bolus can induce abnormal manometric patterns in patients with dysphagia and normal standard manometry. The study group comprised 12 normal volunteers and 22 patients with dysphagia. Manometry was performed using 10 wet swallows followed by 10 swallows of marshmallow. The results show: (1) in normal subjects the mean contraction amplitude is significantly greater (P less than 0.035) and the velocity of propagation significantly slower (P less than 0.003) for soft solid swallows compared with wet swallows; (2) in normal subjects there are fewer abnormal contractions after soft solid swallows than after wet swallows; (3) in 15 patients, soft solid swallows induced non-peristaltic contractions and/or contractions of extreme amplitude and/or duration that were not observed after wet swallows; (4) in patients, the probability of inducing abnormal contractions after soft solid swallows is significantly greater than after wet swallows (P less than 0.0001). We conclude that soft solid swallowing is useful in the study of patients with dysphagia.

Penetrating thoracic wounds caused by plastic bullets.

Thoracic penetrating injuries caused by a new plastic bullet were studied to determine the nature of the wounds and the appropriate management. Twenty-six casualties from the Israeli-Palestinian conflict (Intifada) were included. The organs most commonly involved were lung (n = 21), bony chest wall (n = 9), heart (n = 3), and diaphragm. Bleeding was at least moderate in 20 patients, amounting in all patients to an average of 975 ml. Thoracotomy was required in 11 patients (42%) mainly because of cardiac injury (n = 3) and aortic or other arterial bleeding (n = 3). Simple oversewing of severed organs (n = 8) or ligation of bleeding vessels (n = 3) was satisfactory. Two patients died (7.7% mortality); one after major liver resection; the other was dead on arrival. We conclude that plastic bullets have a linear course unless displaced by the bony chest wall, when they tend to fragment and cause simple fractures. Fired from a presumed range of at least 70 m, plastic bullets behave like low-velocity missiles, and tissue destruction is minimal. Management should be similar to that of civilian thoracic penetrating trauma.