Published Science

We describe vitamin D deficiency rickets in an infant nursed with soybean milk (not specifically designed for infants) instead of cow's milk-based infant formula. Symptoms included irritability and carpopedal spasm when crying. The infant's condition improved with nutrition by vitamin-enriched cow's milk-based infant formula, oral administration 1 alpha-hydroxy vitamin D3 and exposure to sunlight. Content analysis of the milk showed very low calcium, phosphate, magnesium and vitamin D levels compared to cow's milk-based infant milk formulas. This case highlights the unsuitability of soybean milk as the sole provider of infant nutrition and demonstrates the false perception that soybean milk is a healthy food for infants. It is necessary to be cautious about not only health claims for soybean milk, but also today's health and natural food booms. Social enlightenment and correction of such misperceptions are necessary.

Many drugs have been associated with QTc prolongation and, in some cases, this is augmented by concomitant administration with metabolic inhibitors. The effects of 6 antipsychotics on the QTc interval at and around the time of estimated peak plasma/serum concentrations in the absence and presence of metabolic inhibition were characterized in a prospective, randomized study in which patients with psychotic disorders reached steady-state on either haloperidol 15 mg/d (n = 27), thioridazine 300 mg/d (n = 30), ziprasidone 160 mg/d (n = 31), quetiapine 750 mg/d (n = 27), olanzapine 20 mg/d (n = 24), or risperidone 6–8 mg/d increased to 16 mg/d (n = 25/20). Electrocardiograms (ECGs) were done at estimated Cmax at steady-state on both antipsychotic monotherapy and after concomitant administration of appropriate cytochrome P-450 (CYP450) inhibitor(s). Mean QTc intervals did not exceed 500 milliseconds in any patient taking any of the antipsychotics studied, in the absence or presence of metabolic inhibition. The mean QTc interval change was greatest in the thioridazine group, both in the presence and absence of metabolic inhibition. The presence of metabolic inhibition did not significantly augment QTc prolongation associated with any agent. Each of the antipsychotics studied was associated with measurable QTc prolongation at steady-state peak plasma concentrations, which was not augmented by metabolic inhibition. The theoretical risk of cardiotoxicity associated with QTc prolongation should be balanced against the substantial clinical benefits associated with atypical antipsychotics and the likelihood of other toxicities.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.

OBJECTIVES: To review the evidence on the diet and nutrition causes of obesity and to recommend strategies to reduce obesity prevalence. DESIGN: The evidence for potential aetiological factors and strategies to reduce obesity prevalence was reviewed, and recommendations for public health action, population nutrition goals and further research were made. RESULTS: Protective factors against obesity were considered to be: regular physical activity (convincing); a high intake of dietary non-starch polysaccharides (NSP)/fibre (convincing); supportive home and school environments for children (probable); and breastfeeding (probable). Risk factors for obesity were considered to be sedentary lifestyles (convincing); a high intake of energy-dense, micronutrient-poor foods (convincing); heavy marketing of energy-dense foods and fast food outlets (probable); sugar-sweetened soft drinks and fruit juices (probable); adverse social and economic conditions-developed countries, especially in women (probable). A broad range of strategies were recommended to reduce obesity prevalence including: influencing the food supply to make healthy choices easier; reducing the marketing of energy dense foods and beverages to children; influencing urban environments and transport systems to promote physical activity; developing community-wide programmes in multiple settings; increased communications about healthy eating and physical activity; and improved health services to promote breastfeeding and manage currently overweight or obese people. CONCLUSIONS: The increasing prevalence of obesity is a major health threat in both low- and high income countries. Comprehensive programmes will be needed to turn the epidemic around.

Omega-3 or n -3 fatty acids, especially docosahexaenoic acid, are important structural lipids in the brain. Their deficiency leads to a number of sensory, cognitive and behavioral effects. In previous studies, we showed that n -3 deficiency led to a decrease in the neuronal size of a number of brain regions in young rats. In particular, the neuronal size in the hippocampus CA1-CA3 layers decreased with a slight increase in the volumes of these layers. Therefore, we asked whether fatty acid deficiency could affect rat brain morphology in older animals. To address this question, we carried out gross morphological analysis using Magnetic Resonance Imaging on the gray and white matter volumes of brains in older rats (>15 months) that were raised on n -3 deficient diets for three generations. We did not detect any differences in the total or regional gray and white matter volumes of brains of old rats maintained on a n -3 deficient or supplemented diet.

Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0.50, P<0.001) and current (r 0.57, P<0.001) tea intake, and isoferulic acid was related to usual (r 0.26, P=0.008) and current (r 0.18, P

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Atherosclerosis constitutes the main pattern of cardiovascular disease and leads to thickening of the intima with plaque formation and eventual occlusion of the arterial lumen. A large amount of evidence links advanced glycation end products (AGEs) with the development or progression of atherosclerosis, regardless of the diabetic status. AGEs are a heterogenous group of compounds formed by the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. Although AGEs are formed endogenously in the body, diet has recently been recognized as an important exogenous source. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE approaches.

Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to re-align our modern milieu with our ancient genome in an effort to improve cardiovascular health.

A key goal of pre-exercise nutritional strategies is to maximize carbohydrate stores, thereby minimizing the ergolytic effects of carbohydrate depletion. Increased dietary carbohydrate intake in the days before competition increases muscle glycogen levels and enhances exercise performance in endurance events lasting 90 min or more. Ingestion of carbohydrate 3-4 h before exercise increases liver and muscle glycogen and enhances subsequent endurance exercise performance. The effects of carbohydrate ingestion on blood glucose and free fatty acid concentrations and carbohydrate oxidation during exercise persist for at least 6 h. Although an increase in plasma insulin following carbohydrate ingestion in the hour before exercise inhibits lipolysis and liver glucose output, and can lead to transient hypoglycaemia during subsequent exercise in susceptible individuals, there is no convincing evidence that this is always associated with impaired exercise performance. However, individual experience should inform individual practice. Interventions to increase fat availability before exercise have been shown to reduce carbohydrate utilization during exercise, but do not appear to have ergogenic benefits.

BACKGROUND: Plasma cystathionine measurement may be a useful complement to total homocysteine measurement in the assessment of B vitamin status. Information on the within-person variation in cystathionine is currently sparse. OBJECTIVE: The goal was to study the daily variation in plasma cystathionine concentrations in healthy subjects. DESIGN: Twelve subjects (aged 22-29 y) were followed for 24 h. During the observation period, the subjects received a breakfast (containing 15-18 g protein) at 0900 and a beef dinner (containing approximately 50 g protein) at 1500. Multiple blood samples for metabolite analyses were collected during the day, and a final sample was obtained the next morning. The results are expressed as medians and interquartile ranges. RESULTS: All subjects had normal fasting cystathionine concentrations [0.120 (0.100-0.160) micro mol/L]. Cystathionine concentrations increased significantly after breakfast, reached a maximum after 4 h of 142.4% (100.0-170.3%) of the fasting concentration, and then declined to fasting concentrations before dinner. After dinner, plasma cystathionine started to increase within 0.5 h and reached a maximum after 6 h [281.3% (194.1-351.4%) of the concentration measured before dinner]. The changes in plasma methionine and total homocysteine concentrations during the day were less pronounced. CONCLUSION: Food intake, even of foods with low protein content, causes an increase in plasma cystathionine concentrations that is more pronounced than the concomitant changes in total homocysteine and methionine. In studies including plasma cystathionine measurement, blood sampling in the fasting state should be considered.

Background/Aims Obesity has become a global epidemic, and a major preventable cause of morbidity and mortality. Management strategies and treatment protocols are however poorly developed and evaluated. The aim of the Counterweight Programme is to develop an evidence-based model for the management of obesity in primary care. Methods The Counterweight Programme is based on the theoretical model of Evidence-Based Quality Assessment aimed at improving the management of obese adults (18–75 years) in primary care. The model consists of four phases: (1) practice audit and needs assessment, (2) practice support and training, (3) practice nurse-led patient intervention, and (4) evaluation. Patient intervention consisted of screening and treatment pathways incorporating evidence-based approaches, including patient-centred goal setting, prescribed eating plans, a group programme, physical activity and behavioural approaches, anti-obesity medication and weight maintenance strategies. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. Eighty practices were recruited of which 18 practices were randomized to act as controls and receive deferred intervention 2 years after the initial audit. Results By February 2004, 58 of the 62 (93.5%) intervention practices had been trained to run the intervention programme, 47 (75.8%) practices were active in implementing the model and 1256 patients had been recruited (74% female, 26% male, mean age 50.6 years, SD 14). At baseline, 75% of patients had at one or more co-morbidity, and the mean body mass index (BMI) was 36.9 kg/m2 (SD 5.4). Of the 1256 patients recruited, 91% received one of the core lifestyle interventions in the first 12 months. For all patients followed up at 12 months, 34% achieved a clinical meaningful weight loss of 5% or more. A total of 51% of patients were classed as compliant in that they attended the required level of appointments in 3, 6, and 12 months. For fully compliant patients, weight loss improved with 43% achieving a weight loss of 5% or more at 12 months. Conclusion The Counterweight Programme is an evidence-based weight management model which is feasible to implement in primary care.

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = -0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (\textgreater3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = -2.0 mg/dL, P = 0.005), independent of weight loss. In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. © 2004 by Elsevier Inc.

Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard.

The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults can be a challenging process because it includes making judgments based on clinical interviews, rating scale results, informant ratings, and objective supporting evidence. The patient evaluation should gather information on the severity and frequency of symptoms, the establishment of childhood onset of symptoms, the chronicity and pervasiveness of symptoms, and the impact of symptoms on major life activities. Some of the rating scales being used in the adult population are the Conners' Adult ADHD Rating Scales, the Brown Attention-Deficit Disorder Scale for Adults, the Wender Utah Rating Scale, the ADHD Rating Scale and ADHD Rating Scale-IV, the Current Symptoms Scale, and the recently-developed Adult ADHD Self-Report Scale-v1.1 Symptom Checklist. More research is needed to establish the usefulness of self-administered rating scales compared with investigator-administered scales in the assessment and diagnosis of adult ADHD.

The existence of atherosclerosis has been recognized for over 500 years; as a pathological condition, it has been recognized for over 150 years. Understanding of atherosclerotic vascular disease {(AVD)} has evolved most dramatically over the past 25 years with the growth of the field of vascular biology.1 Numerous studies have described this disease as a diffuse and progressive process with a variable distribution and clinical presentation that is dependent on the regional circulation involved. Factors that may influence these differences include the size and structure of the affected artery, local and regional flow, changes in microcirculatory alterations, and end-organ damage. This report discusses the general concepts of atherosclerosis, pathophysiology, microcirculatory disturbances, regional responses to atherosclerosis and ischemia, and recommendations for future research, programs, and advocacy.

This article examines the existence, description, perception, treatment, and outcome of symptoms consistent with autistic disorder in nineteenth-century London, England, based on case histories from the notes of Dr William Howship Dickinson at Great Ormond Street Hospital for Children. Three cases meeting the DSM-IV criteria for autistic disorder are described in detail. Other cases in which autistic traits are described are briefly summarized. The article explores the environment of contemporary medical practice, beliefs about childhood brain disorders, and social practice regarding children with brain disorders, and the impact of these factors on assessment and treatment. It correlates Dickinson’s observations with current research on autism, providing information about children with autism before the condition was formally named in 1943.

Easy bruising and bleeding are not only characteristic manifestations of clotting and platelet disorders, they are also prominent features in some heritable collagen disorders, such as the Ehlers–Danlos syndromes (EDS). The EDS comprise a heterogeneous group of connective tissue diseases sharing clinical manifestations in skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding the fibrillar collagens type I, III and V, or in genes coding for enzymes involved in the post-translational modification of these collagens. Easy bruising is, to a variable degree, present in all subtypes of EDS, and is because of fragility of the capillaries and the perivascular connective tissues. Vascular fragility affecting medium-sized and large arteries and veins is typically observed in the vascular subtype of EDS, caused by a molecular defect in collagen type III, an important constituent of blood vessel walls and hollow organs. Extensive bruising, spontaneous arterial rupture, leading to severe internal bleeding or premature death, and rupture of hollow organs, such as the intestine or the gravid uterus are predominant features of this subtype. Haematological studies including evaluation of clotting factors, platelet aggregation and bleeding time are usually normal in patients with EDS, except for the Hess test (Rumple–Leede test), which may be abnormal, indicating capillary fragility. In some forms of EDS confirmation of the clinical diagnosis and subtype is possible with biochemical and molecular studies.

OBJECTIVES To determine the prevalence and severity of dental caries in a sample of urban Fijian school children. DESIGN Cross-sectional. SAMPLE AND METHODS Children aged between 6 and 8 years who attended one of four primary schools in different localities of Suva completed self-report questionnaires and were examined for dental caries. RESULTS A total of 704 children (response rate = 72.4%) returned questionnaires and were examined dentally. The prevalence of dental caries in the primary dentition was 87.6% and in the permanent dentition, 46.7%. The mean dfs and mean DFS were 8.43 (SD 7.82) and 2.38 (SD 1.37), respectively. High caries prevalence and severity were associated with infrequent brushing, snacking on sugar-containing foods, having seen a dentist before, and having last visited a dentist because of pain. CONCLUSIONS The caries prevalence of the sample was comparable with findings from a national oral health survey conducted in 1985/86, but the caries severity was greater. As in other developing countries, this may be due to an increased availability of refined sugar products without a concurrent rise in oral health awareness. The study findings contribute to the overall picture of Fijian school children's dental health.

BACKGROUND: Our objective was to analyze a restricted carbohydrate dietary approach compared to a standard low-fat diet plus medication plan as treatment for weight loss and the metabolic syndrome. METHODS: This was a retrospective analysis of patients attending an outpatient weight and metabolism management program, including periodic individual visits combined with either a carbohydrate-restricted diet (with multivitamin and essential fatty acids supplementation) or low-fat/low-calorie diet + phentermine/fenfluramine. The main outcome measurements were total body weight and fasting serum lipid profiles. Clinical data were maintained on standardized flow sheets. RESULTS: One hundred twenty-two patients had complete baseline and follow-up information. Sixty-six were treated with a carbohydrate-restricted diet without medication, and 56 were treated with a combination of low-fat/low-calorie diet and medication. Weight loss occurred in both groups, but was greater in the medication group: the carbohydrate-restricted group lost a mean of 9.5 kg over 15.0 weeks (0.63 kg/week); the low-fat/low-calorie diet + medication group lost a mean of 14.1 kg over a mean duration of 20.2 weeks (0.70 kg/week), p < 0.01. The carbohydrate-restricted group had a greater reduction in triglycerides (p = 0.02) and triglyceride/HDL ratio (p = 0.01), and a greater increase in HDL (p

BACKGROUND: Adherence to antidepressant medication use is a problem in clinical practice. Some authors have posited that combined psychological treatment facilitates adherence to pharmacotherapy. OBJECTIVES: To study the relationship between adherence to use of and efficacy of antidepressant drugs plus psychological treatment vs drug treatment alone in depressive disorders. DATA SOURCES: MEDLINE, Current Contents, PsychInfo, Cochrane Library, and reference lists were searched, from January 1980 to November 2002. STUDY SELECTION: Randomized clinical trials comparing antidepressant treatment alone with antidepressant treatment in combination with a psychological intervention in depressive disorders were considered. The decision to include studies in the meta-analysis was performed by 2 reviewers. DATA EXTRACTION: Three independent reviewers extracted the data, using a precoded form. Methodological quality of the studies was evaluated in terms of allocation concealment and independence of evaluators. DATA SYNTHESIS: Sixteen trials met the inclusion criteria, with 932 patients randomized to pharmacotherapy alone and 910 to combined treatment. Overall, patients receiving combined treatment improved significantly compared with those receiving drug treatment alone (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.38-2.52), but dropouts and nonresponders did not differ in distribution between the 2 treatment modalities (OR, 0.86; 95% CI, 0.60-1.24). Studies longer than 12 weeks showed a significant advantage of combined treatment over drug treatment alone (OR, 2.21; 95% CI, 1.22-4.03), with a significant reduction in dropouts compared with nonresponders (OR, 0.59; 95% CI, 0.39-0.88). These estimates were not affected by study quality. CONCLUSIONS: Psychological treatment combined with antidepressant therapy is associated with a higher improvement rate than drug treatment alone. In longer therapies, the addition of psychotherapy helps to keep patients in treatment. Further studies are needed to investigate whether the improvement in response attributable to the combination of drug treatment and psychotherapy can be achieved by a combination of pharmacotherapy and a compliance-enhancing intervention.

Overweight and obese men and women (24–61 yr of age) were recruited into a randomized trial to compare the effects of a low-fat (LF) vs. a low-carbohydrate (LC) diet on weight loss. Thirty-one subjects completed all 10 wk of the diet intervention (retention, 78%). Subjects on the LF diet consumed an average of 17.8% of energy from fat, compared with their habitual intake of 36.4%, and had a resulting energy restriction of 2540 kJ/d. Subjects on the LC diet consumed an average of 15.4% carbohydrate, compared with habitual intakes of about 50% carbohydrate, and had a resulting energy restriction of 3195 kJ/d. Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass. LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2, compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects. The LF group better preserved lean body mass when compared with the ...

Studies of local adaptation provide important insights into the power of natural selection relative to gene flow and other evolutionary forces. They are a paradigm for testing evolutionary hypotheses about traits favoured by particular environmental factors. This paper is an attempt to summarize the conceptual framework for local adaptation studies. We first review theoretical work relevant for local adaptation. Then we discuss reciprocal transplant and common garden experiments designed to detect local adaptation in the pattern of deme × habitat interaction for fitness. Finally, we review research questions and approaches to studying the processes of local adaptation – divergent natural selection, dispersal and gene flow, and other processes affecting adaptive differentiation of local demes. We advocate multifaceted approaches to the study of local adaptation, and stress the need for experiments explicitly addressing hypotheses about the role of particular ecological and genetic factors that promote or hinder local adaptation. Experimental evolution of replicated populations in controlled spatially heterogeneous environments allow direct tests of such hypotheses, and thus would be a valuable way to complement research on natural populations.

Objective: The present paper reviews the evidence that depression is a risk factor for the development and progression of coronary artery disease (CAD). Methods: MEDLINE searches and reviews of bibliographies were used to identify relevant articles. Articles were clustered by theme: depression as a risk factor, biobehavioral mechanisms, and treatment outcome studies. Results: Depression confers a relative risk between 1.5 and 2.0 for the onset of CAD in healthy individuals, whereas depression in patients with existing CAD confers a relative risk between 1.5 and 2.5 for cardiac morbidity and mortality. A number of plausible biobehavioral mechanisms linking depression and CAD have been identified, including treatment adherence, lifestyle factors, traditional risk factors, alterations in autonomic nervous system (ANS) and hypothalamic pituitary adrenal (HPA) axis functioning, platelet activation, and inflammation. Conclusion: There is substantial evidence for a relationship between depression and adverse clinical outcomes. However, despite the availability of effective therapies for depression, there is a paucity of data to support the efficacy of these interventions to improve clinical outcomes for depressed CAD patients. Randomized clinical trials are needed to further evaluate the value of treating depression in CAD patients to improve survival and reduce morbidity.

Russian-speakers, one of the largest groups of new immigrants in New York, are characterized by high proportions of refugees, and elderly and urban residents. To understand the extent of diabetes and its risks in this population, client data from a large state-wide diabetes prevention program were used. The prevalence of diabetes among Russian-speaking immigrants aged 40 years and older (N=1,008) was 16.9% (95% confidence interval [CI]: 14.6, 19.3). Russian-speaking immigrants also exhibited a high prevalence of obesity, defined by BMI > or = 30 (33.2%, 95% CI: 30.4, 36.2), high blood pressure (53.8%, 95% CI: 50.7, 56.8), and sedentary lifestyle (69.8%, 95% CI: 67.0, 72.6). After adjusting for age, these rates were significantly higher (P

PURPOSE: The epidemiology, classification, pathology, and treatment of diabetic neuropathy are reviewed. SUMMARY: Diabetic peripheral neuropathy is a common complication of diabetes that can cause significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. Sensorimotor neuropathy is marked by pain, paresthesia, and sensory loss. Cardiac autonomic neuropathy (CAN) may contribute to myocardial infarction, malignant arrhythmia, and sudden death. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy. Genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder. The pathology of diabetic neuropathy involves oxidative stress, advanced glycation end products, polyol pathway flux, and protein kinase C activation; all contribute to microvascular disease and nerve dysfunction. For symptom management current evidence from clinical trials supports the use of desipramine, amitriptyline, capsaicin, tramadol, gabapentin, bupropion, and venlafaxine as preferred medications. Citalopram, nonsteroidal antiinflammatory drugs, and opioid analgesics may be used as adjuvant agents. Lamotrigine, oxcarbazepine, paroxetine, levodopa, and alpha-lipoic acid are alternative considerations. Evidence supporting the use of zonisamide, fluoxetine, mexiletine, dextromethorphan, and phenytoin is considered equivocal. Complementary therapies have also shown efficacy. The symptoms of CAN may be ameliorated with fludrocortisone, clonidine, midodrine, dihydroergotamine or caffeine, octreotide, and beta-blockers. Gastroparesis may be treated with metoclopramide or erythromycin. The most promising disease-modifying therapy is ruboxistaurin, which is in Phase III trials. Glycemic control remains the foundation of prevention and the prerequisite of adequate treatment. CONCLUSION: Diabetic neuropathy is a many-faceted complication of diabetes that can be managed symptomatically with an array of drugs.

BACKGROUND: As shown in previous studies vegetarians and especially vegans are at risk for iron deficiency. Our study evaluated the iron status of German female vegans. METHODS: In this cross-sectional study, the dietary intakes of 75 vegan women were assessed by two 9-day food frequency questionnaires. The iron status was analyzed on the basis of blood parameters. RESULTS: Mean daily iron intake was higher than recommended by the German Nutrition Society. Still 42% of the female vegans < 50 years (young women, YW) had a daily iron intake of or = 50 years (old women, OW). In all, 40% (tri-index model (TIM) 20%) of the YW and 12% (TIM 12%) of the OW were considered iron-deficient based on either serum ferritin levels of

BACKGROUND The aim of the present study was to determine whether repeated 60 degrees C sauna treatment improves cardiac arrhythmias in chronic heart failure (CHF) patients, because ventricular arrhythmias are an important therapeutic target in CHF. METHODS AND RESULTS Thirty patients (59+/-3 years) with New York Heart Association functional class II or III CHF and at least 200 premature ventricular contractions (PVCs)/24 h assessed by 24-h Holter recordings were studied. They were randomized into sauna-treated (n=20) or non-treated (n=10) groups. The sauna-treated group underwent a 2-week program of a daily 60 degrees C far infrared-ray dry sauna for 15 min, followed by 30 min bed rest with blankets, for 5 days per week. Patients in the non-treated group had bed rest in a temperature-controlled room (24 degrees C) for 45 min. The total numbers of PVCs/24 h in the sauna-treated group decreased compared with the non-treated group [848+/-415 vs 3,097+/-1,033/24 h, p\textless0.01]. Heart rate variability (SDNN, standard deviation of normal-to-normal beat interval) increased [142+/-10 (n=16) vs 112+/-11 ms (n=8), p\textless0.05] and plasma brain natriuretic peptide concentrations decreased [229+/-54 vs 419+/-110 pg/ml, p\textless0.05] in the sauna-treated group compared with the non-treated group. CONCLUSION Repeated sauna treatment improves ventricular arrhythmias in patients with CHF.

New light is shed on everyday life in the middle ages in Great Britain and continental Europe through this unique survey of its food culture. Students and other readers will learn about the common foodstuffs available, how and what they cooked, ate, and drank, what the regional cuisines were like, how the different classes entertained and celebrated, and what restrictions they followed for health and faith reasons. Fascinating information is provided, such as on imitation food, kitchen humor, and medical ideas. Many period recipes and quotations flesh out the narrative.

Alzheimer's disease (AD) is a common, progressive, neurodegenerative disease that primarily afflicts the elderly. A well-defined risk factor for late onset AD is possession of one or more alleles of the epsilon-4 variant (E4) of the apolipoprotein E gene. Meta-analysis of allele frequencies has found that E4 is rare in populations with long historical exposure to agriculture, suggesting that consumption of a high carbohydrate (HC) diet may have selected against E4 carriers. The apoE4 protein alters lipid metabolism in a manner similar to a HC diet, suggesting a common mechanism for the etiology of AD. Evolutionarily discordant HC diets are proposed to be the primary cause of AD by two general mechanisms. (1) Disturbances in lipid metabolism within the central nervous system inhibits the function of membrane proteins such as glucose transporters and the amyloid precursor protein. (2) Prolonged excessive insulin/IGF signaling accelerates cellular damage in cerebral neurons. These two factors ultimately lead to the clinical and pathological course of AD. This hypothesis also suggests several preventative and treatment strategies. A change in diet emphasizing decreasing dietary carbohydrates and increasing essential fatty acids (EFA) may effectively prevent AD. Interventions that restore lipid homeostasis may treat the disease, including drugs that increase fatty acid metabolism, EFA repletion therapy, and ketone body treatment.

BACKGROUND: A relatively high percentage of energy intake as protein has been shown to increase satiety and decrease energy efficiency during overfeeding. AIM: To investigate whether addition of protein may improve weight maintenance by preventing or limiting weight regain after weight loss of 5-10% in moderately obese subjects. DESIGN OF THE STUDY: In a randomized parallel design, 148 male and female subjects (age 44.2 ± 10.1 y; body mass index (BMI) 29.5 ± 2.5 kg/m 2; body fat 37.2 ± 5.0%) followed a very low-energy diet (2.1 MJ/day) during 4 weeks. For subsequent 3 months weight-maintenance assessment, they were stratified according to age, BMI, body weight, restrained eating, and resting energy expenditure (REE), and randomized over two groups. Both groups visited the University with the same frequency, receiving the same counseling on demand by the dietitian. One group (n=73) received 48.2 g/day additional protein to their diet. Measurements at baseline, after weight loss, and after 3 months weight maintenance were body weight, body composition, metabolic measurements, appetite profile, eating attitude, and relevant blood parameters. RESULTS: Changes in body mass, waist circumference, REE, respiratory quotient (RQ), total energy expenditure (TEE), dietary restraint, fasting blood-glucose, insulin, triacylglycerol, leptin, β-hydroxybutyrate, glycerol, and free fatty acids were significant during weight loss and did not differ between groups. During weight maintenance, the 'additional-protein group' showed in comparison to the nonadditional-protein group 18 vs 15 en% protein intake, a 50% lower body weight regain only consisting of fat-free mass, a 50% decreased energy efficiency, increased satiety while energy intake did not differ, and a lower increase in triacylglycerol and in leptin; REE, RQ, TEE, and increases in other blood parameters measured did not differ. CONCLUSION: A 20% higher protein intake, that is, 18% of energy vs 15% of energy during weight maintenance after weight loss, resulted in a 50% lower body weight regain, only consisting of fat-free mass, and related to increased satiety and decreased energy efficiency.

Tinnitus affects millions of people worldwide, and it signals the presence of several underlying diseases, including hyperinsulinemia. The aim of this study was to evaluate the response to dietary treatment in 80 patients with associated tinnitus and hyperinsulinemia. On the basis of data obtained by a questionnaire, two groups were established: One included patients who followed the prescribed diet; the other group included patients who did not comply with the treatment. The likelihood of improving tinnitus symptoms was fivefold higher in hyperinsulinemic patients who followed the diet than in those who did not (relative risk [RR], 5.34; 95% confidence interval [CI], 1.85-15.37; p

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 +/- 1.9 vs. 25.9 +/- 3.2 kg/m(2); percent body fat, 8.7 +/- 7% vs. 24 +/- 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was approximately 40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT.

BACKGROUND: Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known. OBJECTIVE: To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients. PATIENTS AND METHODS: In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m2, and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment. RESULTS: The weight and body mass index of the patients decreased significantly (P

Attention deficit-hyperactivity disorder (ADHD) is a very common and heterogeneous childhood-onset psychiatric disorder, affecting between 3% and 5% of school age children worldwide. Although the neurobiology of ADHD is not completely understood, imbalances in both dopaminergic and noradrenergic systems have been implicated in the origin and persistence of core symptoms, which include inattention, hyperactivity, and impulsivity. The role of a genetic component in its etiology is strongly supported by genetic studies, and several investigations have suggested that the dopamine transporter gene (DAT1; SLC6A3 locus) may be a small-effect susceptibility gene for ADHD. Stimulant medication has a well-documented efficacy in reducing ADHD symptoms. Methylphenidate, the most prescribed stimulant, seems to act mainly by inhibiting the dopamine transporter protein and dopamine reuptake. In fact, its effect is probably related to an increase in extracellular levels of dopamine, especially in brain regions enriched in this protein (i.e. striatum). It is also important to note that dopamine transporter densities seem to be particularly elevated in the brain of ADHD patients, decreasing after treatment with methylphenidate. Altogether, these observations suggest that the dopamine transporter does play a major role in ADHD. Among the several polymorphisms already described in the SLC6A3 locus, a 40 bp variable number of tandem repeats (VNTR) polymorphism has been extensively investigated in association studies with ADHD. Although there are some negative results, the findings from these reports indicate the allele with ten copies of the 40 bp sequence (10-repeat allele) as the risk allele for ADHD. Some investigations have suggested that this polymorphism can be implicated in dopamine transporter gene expression in vitro and dopamine transporter density in vivo, even though it is located in a non-coding region of the SLC6A3 locus. Despite all these data, few studies have addressed the relationship between genetic markers (specifically the VNTR) at the SLC6A3 locus and response to methylphenidate in ADHD patients. A significant effect of the 40 bp VNTR on response to methylphenidate has been detected in most of these reports. However, the findings are inconsistent regarding both the allele (or genotype) involved and the direction of this influence (better or worse response). Thus, further investigations are required to determine if genetic variation due to the VNTR in the dopamine transporter gene is able to predict different levels of clinical response and palatability to methylphenidate in patients with ADHD, and how this information would be useful in clinical practice.

BACKGROUND: Depression is the fourth most important disease in the estimation of the burden of disease Murray 1996 and is a common problem with prevalence rates estimated to be as high as 8% in young people. Depression in young people is associated with poor academic performance, social dysfunction, substance abuse, suicide attempts, and completed suicide (NHMRC 1997). This has precipitated the development of programmes aimed at preventing the onset of depression. This review evaluates evidence for the effectiveness of these prevention programmes. OBJECTIVES: To determine whether psychological and/or educational interventions (both universal and targeted) are effective in reducing risk of depressive disorder by reducing depressive symptoms immediately after intervention or by preventing the onset of depressive disorder in children and adolescents over the next one to three years. SEARCH STRATEGY: The Cochrane Depression, Anxiety and Neurosis Group trials register (August 2002), MEDLINE (1966 to December Week 3 2002), EMBASE (1980 to January Week 2 2003), PsychInfo (1886 to January Week 2 2003) and ERIC (1985 to December 2002) were searched. In addition, conference abstracts, the reference lists of included studies, and other reviews were searched and experts in the field were contacted. SELECTION CRITERIA: Each identified study was assessed for possible inclusion by two independent reviewers based on the methods sections. The determinants for inclusion were that the trial include a psychological and/or educational prevention programme for young people aged 5 to 19 years-old, who did not meet DSM or ICD criteria for depression and/or did not fall into the clinical range on standardised, validated, and reliable rating scales of depression. DATA COLLECTION AND ANALYSIS: The methodological quality of the included trials was assessed by two independent reviewers according to a list of pre-determined criteria, which were based on quality ratings devised by Moncrieff and colleagues (Moncrieff 2001). Outcome data was extracted and entered into Revman 4.2. Means and standard deviations for continuous outcomes and number of events for dichotomous outcomes were extracted where available. For trials where the required data were not reported or could not be calculated, further details were requested from first authors. If no further details were provided, the trial was included in the review and described, but not included in the meta-analysis. Results were presented for each type of intervention: targeted or universal interventions; and educational or psychological interventions and if data were provided, by gender. Where possible data were combined in meta-analyses to give a treatment effect across all trials. Sensitivity analysis were conducted on studies rated as "adequate" or "high" quality, that is with a score over 22, based on the scale by Moncrieff et al (Moncrieff 2001). The presence of publication bias was assessed using funnel plots. MAIN RESULTS: Studies were divided into those that compared intervention with an active comparison or placebo (i.e. a control condition that resembles the intervention being investigated but which lacks the elements thought to be active in preventing depression) and those that used a "wait-list" or no intervention comparison group. Only two studies fell into the former category and neither showed effectiveness although one study was inadequately powered to show a difference and in the other the "placebo" contained active therapeutic elements, reducing the ability to demonstrate a difference from intervention. Psychological interventions were effective compared with non-intervention immediately after the programmes were delivered with a significant reduction in scores on depression rating scales for targeted (standardised mean difference (SMD) of -0.26 and a 95% confidence interval (CI) of -0.40 to -0.13 ) but not universal interventions (SMD -0.21, 95% CI -0.48, 0.06), with a significant effect maintained on pooling data (SMD -0.26, 95% CI -0.36, -0.15). While small effect sizes were reported, these were associated with a significant reduction in depressive episodes. The overall risk difference after intervention translates to "numbers needed to treat" (NNT) of 10. The most effective study is the targeted programme by Clarke (Clarke 2001) where the initial effect size of -0.46 is associated with an initial risk difference of -0.22 and NNT 5. There was no evidence of effectiveness for educational interventions. Reports of effectiveness for boys and girls were contradictory. The quality of many studies was poor, and only two studies made allocation concealment explicit. Sensitivity analysis of only high quality studies did not alter the results significantly. The only analysis in which there was significant statistical heterogeneity was the sub-group analysis by gender where there was variability in the response to different programmes for both girls and boys. For the most part funnel plots indicate findings are robust for short term effects with no publication bias evident. There are too few studies to comment on whether there is publication bias for studies reporting long-term (12-36 month) follow-up. REVIEWER'S CONCLUSIONS: Although there is insufficient evidence to warrant the introduction of depression prevention programmes currently, results to date indicate that further study would be worthwhile. There is a need to compare interventions with a placebo or some sort of active comparison so that study participants do not know whether they are in the intervention group or not, to investigate the impact of booster sessions to see if effectiveness immediately after intervention can be prolonged, ideally for a year or longer, and to consider practical implementation of prevention programmes when choosing target populations. Until now most studies have focussed on psychological interventions. The potential effectiveness of educational interventions has not been fully investigated. Given the gender differences in prevalence, and the change in these that occurs in adolescence with a disproportionate increase in prevalence rates for girls, it is likely that girls and boys will respond differently to interventions. Although differences have been reported in studies in this review the findings are contradictory and a more definitive delineation of gender specific responses to interventions would be helpful.

Conjugated linoleic acids (CLA) are implicated as anti-carcinogenic, anti-atherosclerosis, and anti-inflammatory agents in a variety of experimental model systems. However, evidence of dietary CLA protection against human mammary cancer risk is mixed and comes from European countries where the death rate from mammary cancer is relatively scarce. Unfortunately, epidemiological data are inconclusive, especially from retrospective studies. Prospective human study evidence will take more time. European values as great as 1.9% CLA in the fat of milk products from grass-fed ruminants has been reported; ordinary monogastric meat and egg products contain substantially less CLA in fat (0.3%). It is now recognized that the principle CLA in ruminant meat and milk is the natural diene, cis (c)-9, trans (t)-11 isomer (rumenic acid) of C18:2 (octadecadienoic acid). Another isomer, C18:2 t-10, c-12, also contributes to the unique biological activity of CLA, but does not readily accumulate in ruminant lipids and is found only in commercial preparations of mixed CLA isomers. Evidence in humans suggested that the role of the dietary mixed isomer CLA in the loss of body fat mass (BFM) was only modest compared with the results from animal model studies, and urine metabolites of prostaglandin F2α (PGF2α), indicative of lipid oxidation stress, have been elevated during supplementation. In addition, the fatty acid C18:1 t-11 (vaccenic) is now believed to be the principle precursor of endogenous c-9, t-11 CLA in both ruminants and monogastrics. This finding helps explain the discrepancy between measured c-9, t-11 CLA originating from the rumen and that secreted in cow's milk. Manipulation of ruminant meat and milk by feeding marine or vegetable oils is clearly associated with increases in vaccenic acid as well. This relationship requires a re-examination of human foods for vaccenic acid content and quantitative measures of CLA endogenous synthesis in humans as well to formulate dietary strategies to capture CLA's potential protective health benefits. © 2004 American Registry of Professional Animal Scientists