Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice.

INTRODUCTION: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. METHODS: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. RESULTS: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. CONCLUSION: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."

On radar and radio exposure and cancer in the military setting.

INTRODUCTION: In 2018, we reported a case series of 47 patients diagnosed with cancer following several years of exposure to high-intensity whole-body radiofrequency radiation (RFR) using the parameter of percentage frequency (PF). Consistent high and statistically significant PFs of hematolymphoid (HL) cancers were found in this group and in four previous reports on RFR-exposed groups in Belgium, Poland and Israel together with increased all-cancers rates. In this paper we report a new series of 46 young cancer patients who were exposed during military service to such radiation. MATERIALS AND METHODS: The new group of patients comprises Israeli soldiers previously exposed to occupational RFR. The patients were self-selected to enroll in the research in cooperation with an NGO assisting patients with administrative counseling and legal and social services. The new group of patients was studied with respect to distribution (proportion) of cancer types using the method of PF. When possible, cancer risk ratios (RR) were estimated too. The results are compared to those of other occupational groups in three countries. RESULTS: Median age at diagnosis was 23 years; duration of exposure was between 1 and 3 years and the latencies were short, median 4.6 years. The PF of HL cancers was 41.3%, 95% CI (27%-57%), versus 22.7% expected in non-exposed subjects matched for age and gender profiles, p = 0.003; 19 out of the 46 patients had HL cancers. The PF of Hodgkin lymphoma cancers was 21.7%, 95%CI (11%-36%), versus 11.6% expected, p = 0.033. For a subgroup of 6 patients, the number of soldiers in the units was known, and we were able estimate approximately the overall cancer risk ratio (RR) after 8 years as being 8.0 with 95% CI (2.9, 17), p < 0.002, with only 0.75 cases expected from the Cancer Registry data. In this subgroup, there were 3 HL cancer cases and 3 non-HL cases. Sarcoma PF was higher than expected, 7 out of the 46 patients were diagnosed with sarcoma, PF = 15.2%, 95%CI (6.3%-28.9%), p = 0.04 versus the expected PF of 7%. CONCLUSION: The HL PF was high and consistent with previous reports. Epidemiological studies on excess risk for HL and other cancers, brain tumors in cellphone users, and experimental studies on RFR and carcinogenicity strongly point to a cause-effect relationship. It is mandatory to reduce the RFR exposure of all personnel to that of the typical community levels, including the peak level of radar pulses. Radiation protection, safety instructions, cancer risk warnings and quantitative data on individual exposure together with regular medical monitoring must be instituted for all personnel exposed to such risks. The findings from our study add to the growing body of evidence underscoring the gross inadequacy of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) thermal standards. Based on our findings and on the previous accumulated research, we endorse the recommendations to reclassify RFR exposure as a human carcinogen, International Agency for Research on Cancer (IARC) group 1.

Comparisons in polypharmacy over a decade in community-dwelling older adults-findings from Israel national health and nutrition surveys.

BACKGROUND: Polypharmacy increases with age and is associated with serious health and economic costs. This study reports changes over a decade in medication-use patterns and polypharmacy, in Israeli community-dwelling older adults aged ≥ 65 years. METHODS: Demographic and health data from two representative national health cross-sectional surveys - MABAT ZAHAV 1 (MZ1) in 2005-2006, and MZ2 in 2014-2015 were analyzed. Polypharmacy was defined as use of ≥ 5 medications. Risk factors for polypharmacy were estimated by multivariable logistic regression with adjusted odds ratios (aOR) and their 95% confidence intervals (CI). RESULTS: Self-reported data on medications taken were available for 1647 participants (91.5%) in MZ1, and for 833 participants (80.2%) in MZ2, 55% women, and about 20% aged ≥ 80, in both surveys. The prevalence of polypharmacy was significantly lower in MZ2 than in MZ1: 64.2% versus 56.3%, p = .0001; with an aOR (95%CI) of 0.64 (0.52, 0.80). The most commonly taken drugs were for hypertension (27.0%, 25.3%), dyslipidemia (9.7%, 12.4%) and anticoagulation (9.2%, 9.8%). For approximately 10% of drugs, indications were either unknown or incorrect. Polypharmacy was significantly associated with poor self-health assessment 2.47 (1.99, 3.06), ≥ 4 versus 1-3 chronic illnesses 6.36 (3.85, 10.50), and age ≥ 80 versus younger 1.72 (1.32, 2.24). Similar associations were observed with major polypharmacy of ≥ 8 medications. CONCLUSION: Polypharmacy, although reduced in the last decade, requires constant attention, especially concerning lack of knowledge of indications which leads to poor adherence and adverse side effects. Health-care teams should carry out regular medicine reconciliation in at-risk elderly patients.

Beta-carotene as a novel therapy for the treatment of "Autistic like behavior" in animal models of Autism.

Autism-affected individuals are characterized by lower plasma oxytocin and its ectoenzyme regulator CD38. Oxytocin, a hypothalamic hormone secreted upon the release of CD38, plays a role in social behavior and bonding. All-trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. We investigated the role of beta-carotene in rescuing autistic-like behavior in BALB/c and BTBR mice. Beta-carotene derivatives are preferred as they are neither toxic nor teratogenic. Beta-carotene at 0.1-5.0 mg/kg was administered orally to BALB/c and BTBR newborn mice on days 1-7. They were tested at age 2-3 months for five behavioral tests for "autism"; in addition, brain CD38, oxytocin, oxytocin receptor, Brain Derived Neurotrophic Factor (BDNF) and retinoic acid receptor gene expression, serum oxytocin levels, and neurological score were evaluated. Beta-carotene administered at birth significantly increased T-maze alternations and led to longer time spent with an unfamiliar mouse in the "three-chamber test" and less time spent in the empty chamber. Furthermore, enhanced activity in the open field test; increased time spent in the reciprocal social interaction test; decreased grooming and bedding behaviors; and enhanced brain CD38, oxytocin, oxytocin receptor, BDNF, retinoic acid gene expression, and serum oxytocin levels. No changes in neurological score were observed. Beta-carotene oral supplementation to BALB/c and BTBR mice at birth significantly reduced restricted and stereotyped behaviors and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity. Thus, beta-carotene administered after birth to newborns of families predisposed to "autism" has the potential to prevent/ameliorate" autistic like behavior". These results support further clinical studies.

Demographic and lifestyle factors associated with adherence to the Mediterranean diet in relation to overweight/obesity among Israeli adolescents: findings from the Mabat Israeli national youth health and nutrition survey.

OBJECTIVE: To investigate demographic and lifestyle factors associated with adherence to the Mediterranean diet (MD) in Israeli adolescents. DESIGN: Cross-sectional. SETTING: School-based. SUBJECTS: Schoolchildren (n 5268) aged 11-19 years answered self-administered questionnaires on food consumption, eating habits and lifestyle; a subset (n 578) also completed 24 h food recalls. RESULTS: Using a modified KIDMED index, 25·5 % of the students had poor, 55·2 % had average and 19·3 % had good MD adherence. Jewish middle-school children had the highest proportion (28·2 %) of poor MD adherence. Olive oil usage, derived from 24 h food recalls, was 18·1 % in Jewish families v. 71·1 % in Arab homes. In Jewish boys, the odds (OR; 95 % CI) of having poor MD adherence was higher in those who watched television/videos/listened to music for ≥2 h/d (1·25; 0·98, 1·58) and those who sometimes/don't read food labels (1·69; 1·31, 2·18). In Jewish girls, the odds for having poor MD adherence was significantly higher in those whose mother's schooling was <12 years (2·06; 1·41, 3·00) and those who sometimes/don't read food labels (1·35; 1·08, 1·69). In Arab boys, watching television/videos/listening to music for ≥2 h/d was significantly associated with poor MD adherence (1·89; 1·16, 3·07). In Arab girls, no aerobic activity or ball games weekly was associated with poor MD adherence (1·38; 0·91, 2·09). CONCLUSIONS: Israeli adolescents had overall a high rate of poor MD adherence. Jewish middle-school children were at the highest risk. Interventions aimed at increasing physical activity, reducing sedentary time, improving mother's education and promoting reading of food labels are recommended.

Health-related quality of life changes and weight reduction after bariatric surgery vs. a weight-loss program.

BACKGROUND: The present study compared the outcome of bariatric surgery against a uniform high-level weightloss program which included vigorous physical exercises, behavior modification and nutritional advice. METHOD: 44 subjects who underwent bariatric surgery and 47 subjects participating in a weight-loss program completed the Medical Outcomes Study Short Form- 36 (SF-36), the Mental Health Inventory (MHI) and the Rosenberg Self-Esteem scale, prior to surgery/diet and one year afterwards. RESULTS: Post-surgery subjects had a greater mean weight loss (34.70% ± 11.94) than subjects in the weight-loss program, even though their weight reduction was also clinically significant (9.23% ± 8.31). Post-surgery subjects showed significant improvements in SF-36, MHI, and selfesteem. The diet group improved in SF-36 total score, physical functioning, health perceptions, and vitality scales. LIMITATIONS: Differences in background variables and short follow-up. CONCLUSIONS: Surgery outcomes were significantly better in terms of both weight reduction and psychological adjustment compared to highly motivated participants in a prestigious, cutting edge weight-loss program.

Tell me what you eat and I will tell you your sociotype: coping with diabesity.

The term sociotype has been introduced to describe the dynamic relationship of an individual with his/her social environment throughout life. The sociotype is a conceptual framework to highlight, in addition to bio-medical pathways, the psycho-social and environmental factors necessary to understand responses to life stresses and patient self-management for chronic illness. The sociotype interacts with genotype expression through mate selection and metabolic programming, and with the phenotype to determine adaptation throughout life from birth to old age. Following on the work of Antonovsky, Engel, and McEwen, and others in the life and social sciences, the sociotype details and expands the many factors generally included in the environmental influences on a person's life identified here as the domains of health, relationships, and environment. Physiological mediators for sociotypic influences include: adrenal steroids and the sympathetic nervous system (allostatic load), and oxytocin (social neuroscience). The biological pathways are multiple through nutrition (essential dietary-derived amino- and fatty acids for neurotransmitter synthesis, caloric restriction, and diet-gene interactions), epigenesis, and metabolic programming. Nutrition influences growth and development, fertility and longevity, and also determines susceptibility to non-communicable diseases such as cardiovascular disease and cancer, and particularly diabetes and obesity, through in-utero effects, the development of intestinal flora (microbiome), and chronic stress. Thus the sociotype and nutrition are reciprocally related in both health and disease.

[Who will take care of the caretaker? Lifestyle recommendations for physicians].

A healthy lifestyle is the mainstay of preventive medicine. HeaLthcare personnel might disregard keeping a healthy diet and exercise habits, perhaps due to feeling protected by their own knowledge. Physicians might under-diagnose their own overweight status, and have been shown in some studies to display lower rates of healthy behaviors compared with the general population. This review presents the availabLe data on physicians' own lifestyle habits, and discusses the importance of these for both their own health, and for the benefit of their patients. We supply several healthy lifestyle recommendations based on national and international guidelines, and adapt them to the clinic and hospital settings. Eating a healthy diet, and performing at least 150 minutes of aerobic exercise a week, with additional resistance exercises 2-3 times a week, will benefit all caretakers--both personally and professionally.

Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals.

Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with that of canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergic systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol, serotonin (5-HT) (P<.056), dopamine, neuropeptide Y (NPY) and Ca(2+)/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 and brain-derived neurotrophic factor. In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems.

Limited English proficiency is a barrier to receipt of advice about physical activity and diet among Hispanics with chronic diseases in the United States.

The prevalence of obesity, diabetes, and cardiovascular disease is reaching epidemic proportions among Hispanics in the United States. Health care providers play an important role in motivating patients to make healthful lifestyle changes to reduce the burden of such conditions. Data from the US 2000 National Health Interview Survey was analyzed to determine differences in report of physician-provided physical activity and/or dietary advice by level of English proficiency among obese Hispanics or those who reported having diabetes or cardiovascular disease and who contacted a physician during the past year (n=1,186). Only one third of the sample reported receiving advice to increase their physical activity or to improve their dietary habits; one fifth reported receipt of advice about both. English-proficient Hispanics were about 50% more likely to report receiving advice on physical activity (adjusted odd ratio [AOR]=1.5; 95% confidence interval [CI]: 1.1 to 2.1), diet (AOR=1.5; 95% CI: 1.1 to 2.2) or both (AOR=1.6; 95% CI: 1.1 to 2.3), as compared with limited English-proficient Hispanics, after controlling for health insurance coverage and number of visits to a physician during the last year. Sex, age, region of residence, level of education, annual family income, and smoking status were not significantly associated with receiving physical activity and/or dietary advice. In order to address racial health disparities, and lower the burden of chronic illness, culturally sensitive strategies must be implemented to enhance delivery of effective health-promotion messages by physicians, particularly among at-risk communities.

Limited English proficiency is a barrier to receipt of advice about physical activity and diet among Hispanics with chronic diseases in the United States.

The prevalence of obesity, diabetes, and cardiovascular disease is reaching epidemic proportions among Hispanics in the United States. Health care providers play an important role in motivating patients to make healthful lifestyle changes to reduce the burden of such conditions. Data from the US 2000 National Health Interview Survey was analyzed to determine differences in report of physician-provided physical activity and/or dietary advice by level of English proficiency among obese Hispanics or those who reported having diabetes or cardiovascular disease and who contacted a physician during the past year (n=1,186). Only one third of the sample reported receiving advice to increase their physical activity or to improve their dietary habits; one fifth reported receipt of advice about both. English-proficient Hispanics were about 50% more likely to report receiving advice on physical activity (adjusted odd ratio [AOR]=1.5; 95% confidence interval [CI]: 1.1 to 2.1), diet (AOR=1.5; 95% CI: 1.1 to 2.2) or both (AOR=1.6; 95% CI: 1.1 to 2.3), as compared with limited English-proficient Hispanics, after controlling for health insurance coverage and number of visits to a physician during the last year. Sex, age, region of residence, level of education, annual family income, and smoking status were not significantly associated with receiving physical activity and/or dietary advice. In order to address racial health disparities, and lower the burden of chronic illness, culturally sensitive strategies must be implemented to enhance delivery of effective health-promotion messages by physicians, particularly among at-risk communities.

Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation.

BACKGROUND/AIMS: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease. METHODS: CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL. RESULTS: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor. CONCLUSIONS: The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.

[Childhood obesity--assessment, prevention and treatment].

As in other parts of the western world, the rates of pediatric overweight and obesity are also rising in Israel. This fact warrants immediate action by several government offices and health care providers, and also by the trinity of physician, parent(s) and child. An overweight child is likely to remain undiagnosed if relying on observation alone, unless height and weight are objectively measured by the caring medical staff. This review is based on recommendations on the assessment, prevention, and treatment of children and youth who are overweight and obese, recently published on behalf of the American Medical Association and additional health organizations. In general, preventing and treating pediatric obesity is fairly similar: adhering to a healthy lifestyle which emphasizes healthy food choices and habits, regular physical activity, and limiting screen time. Treating and preventing obesity is a timely, but extremely difficult task. Medical personnel and parents should be continuously educated in this field, while supplied with practical tools for childhood lifestyle modification.

Psychosocial predictors of weight loss and psychological adjustment following bariatric surgery and a weight-loss program: the mediating role of emotional eating.

OBJECTIVE: To examine a structural equation model of the effects of personal and interpersonal factors on treatment outcome of bariatric surgery and weight-loss program. METHOD: Forty-four participants of the surgery group and 47 participants of the diet group completed questionnaires before treatment and 1 year afterward. Predictor measures are as follows: social support, motivation for control, sense of control, self-esteem, neuroticism, fear of intimacy, and emotional eating (EE). OUTCOME MEASURES: Weight loss, quality of life, and mental health. RESULTS: Neurotic predisposition (NP), a latent variable indicated by neuroticism, low self-esteem, and fear of intimacy, had an effect on weight loss that was fully mediated by EE. NP also had an effect on quality of life improvement that was fully mediated by EE and weight loss in both treatment groups. DISCUSSION: Both NP and EE predict outcome of obesity treatments, but EE is the more proximal variable that mediates the effect of NP.

Prevalence and determinants of physical activity and lifestyle in relation to obesity among schoolchildren in Israel.

OBJECTIVE: To describe the relationships between physical activity, lifestyle determinants and obesity in adolescent Israeli schoolchildren.Design and settingCross-sectional survey. SUBJECTS: The MABAT Youth Survey was a nationally representative, school-based study of youth in grades 7 to 12 (ages 11-19 years). METHODS: Self-administered questionnaires assessed health behaviours and anthropometric indices were measured. Logistic regression analysis was used to examine the associations between obesity, physical activity, socio-economic status and other lifestyle habits. One-way ANOVA was used to determine mean physical activity levels (MET values) by BMI categories. RESULTS: The prevalence of overweight was 13-15 % and of obesity 4-9 % depending on gender and ethnicity, and was higher among the non-Jewish sectors. Thirty-six per cent and 57 % of Jewish girls and boys, and 40 % and 58 % of non-Jewish girls and boys, respectively, were optimally active. Boys from low socio-economic schools and those who slept for less than 6 h at night were less active. Girls from middle school were found to be 53 % more optimally physically active among Jews, and 89 % more among non-Jews, compared with girls from high school (P = 0.001); girls with less educated parents were also less physically active. No clear relationship was found between the level of obesity and physical activity. CONCLUSIONS: Physical inactivity was strongly related to gender, age, social status, sleeping habits, hookah smoking, and parental educational status. Education and intervention programmes should focus on these risk factors.

2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist, in various rat tissues during the evolution of experimental cholestatic liver disease.

BACKGROUND/AIM: Changes in tissue levels of 2-arachidonoylglycerol (2-AG), an endocannabinoid, during the evolution of bile duct ligation (BDL) may indicate that endocannabinoids have a role in the hemodynamic changes that occur in this condition. METHODS: 2-AG levels, in various organs and vascular beds of BDL rats, 2 and 4 weeks post surgery, were determined. Untouched and sham-operated (SO) rats were used as controls. RESULTS: 2-AG content of a specific organ was not a static finding and depended on the rat's age, the time from the surgical procedure and the type of procedure. The most pronounced changes were observed in BDL rats 4 weeks post surgery. In these rats, hepatic, pulmonary, cardiac and renal medullary and papillary 2-AG levels were highest observed. No changes in splenic, aortic and renal cortical 2-AG levels were observed. In addition a stepwise increase in 2-AG levels from the cortex to the papilla was detected and was followed by a decrease in creatinine clearance. CONCLUSIONS: 2-AG probably has a role in the pathophysiologic changes in the liver, heart, lung and kidney that follows BDL.

Familial aggregation of red blood cell membrane fatty acid composition: the Kibbutzim Family Study.

The fatty acid composition of membranes plays an important role in health and diseases. Whether genetic factors play a role in interindividual variability in membrane fatty acid levels has received limited attention. Using variance decomposition methods, we estimated the heritability of red blood cell (RBC) membrane fatty acids in an unselected population sample of 80 families (205 male and 212 female subjects) living in kibbutz settlements in Israel. Fatty acid levels were measured by gas chromatography. We estimated that polygenes explained 40% to 70% of the sex- and age-adjusted interindividual variability in all RBC fatty acids: saturated, monounsaturated, and polyunsaturated. The heritability estimates remained very similar after further adjustment for smoking, alcohol consumption, physical activity, lipoproteins, body mass index, waist to hip ratio, education, and religiosity. In bivariate genetic analyses, we observed positive genetic correlations for the fatty acid pairs 20:4n6-22:6n3 and 20:5n3-22:6n3, and negative genetic correlations for the pairs 16:0-20:4n6, 16:0-22:6n3, 18:1n9-20:3n6, 18:2n6-20:4n6, 18:2n6-24:0, and 20:3n6-20:4n6, suggesting that shared effects of the same sets of loci account for 12% to 30% of the additive genetic variance in these pairs of fatty acids. This study suggests a considerable polygenic component for all RBC membrane fatty acids and provides evidence that shared genetic effects account for the additive genetic variance in various fatty acid pairs. Future studies are needed to map the genes underlying the interindividual variation in these inherited phenotypes.

Determinants of disordered eating behaviors among Israeli adolescent girls.

Eating behaviors were assessed by a modified SCOFF questionnaire in a National representative cross-sectional study among 2978 Israeli schoolgirls. The mean age was 14.7. Thirty percent met the criteria for disordered eating. Being Jewish or underweight reduced the odds for disordered eating. The following increased the risk: dieting, early onset of menarche, being overweight or obese, and suffering from constipation. School socio-economic status, physical activity, and smoking status were not contributory. These results help identify possible interventions to prevent the development of disordered eating behaviors.

The synthetic cannabinoid HU-210 attenuates neural damage in diabetic mice and hyperglycemic pheochromocytoma PC12 cells.

Diabetic neuropathy (DN) is a common complication of diabetes mellitus resulting in cognitive dysfunction and synaptic plasticity impairment. Hyperglycemia plays a critical role in the development and progression of DN, through a number of mechanisms including increased oxidative stress. Cannabinoids are a diverse family of compounds which can act as antioxidative agents and exhibit neuroprotective properties. We investigated the effect of the synthetic cannabinoid HU-210 on brain function of streptozotocin (STZ)-induced diabetic mice. These animals exhibit hyperglycemia, increased cerebral oxidative stress and impaired brain function. HU-210, through a receptor independent pathway, alleviates the oxidative damage and cognitive impairment without affecting glycemic control. To study the neuroprotective mechanism(s) involved, we cultured PC12 cells under hyperglycemic conditions. Hyperglycemia enhanced oxidative stress and cellular injuries were all counteracted by HU-210-in a dose dependent manner. These results suggest cannabinoids might have a therapeutic role in the management of the neurological complications of diabetes.

Nutritional status, cognition, and survival: a new role for leptin and AMP kinase.

Although adequate nutrition is essential for optimal neural activity and survival, mild energy restriction may improve cognition and prolong longevity. Energy status is monitored by the cellular AMP-activated protein kinase (AMPK) system, whereas leptin regulates total energy balance. We investigated the roles of AMPK and leptin in cognition and survival under diet restriction (DR). Hippocampal AMPK activity increases with energy restriction. Modest activation (DR to 60%) induces neurogenesis and improves cognition. However, DR to 40% augmented AMPK activity, reduced cognition and catecholamines, and increased neural apoptosis and mortality. Leptin signaling is preserved only in DR to 60%, countering the effects of AMPK "overactivation" by preventing neuroapoptosis, restoring noradrenergic activity and behavioral performance, and increasing longevity. The balance between leptin and AMPK is crucial in determining neuronal fate, cognitive ability, and survival. Should these findings extend to Man, then controlled activation of AMPK may improve neurodegenerative diseases, and leptin may have a new role in treating stress-associated malnutrition.