The Type II NADPH Dehydrogenase Facilitates Cyclic Electron Flow, Energy-Dependent Quenching, and Chlororespiratory Metabolism during Acclimation of Chlamydomonas reinhardtii to Nitrogen Deprivation.

When photosynthetic organisms are deprived of nitrogen (N), the capacity to grow and assimilate carbon becomes limited, causing a decrease in the productive use of absorbed light energy and likely a rise in the cellular reduction state. Although there is a scarcity of N in many terrestrial and aquatic environments, a mechanistic understanding of how photosynthesis adjusts to low-N conditions and the enzymes/activities integral to these adjustments have not been described. In this work, we use biochemical and biophysical analyses of photoautotrophically grown wild-type and mutant strains of Chlamydomonas reinhardtii to determine the integration of electron transport pathways critical for maintaining active photosynthetic complexes even after exposure of cells to N deprivation for 3 d. Key to acclimation is the type II NADPH dehydrogenase, NDA2, which drives cyclic electron flow (CEF), chlororespiration, and the generation of an H(+) gradient across the thylakoid membranes. N deprivation elicited a doubling of the rate of NDA2-dependent CEF, with little contribution from PGR5/PGRL1-dependent CEF The H(+) gradient generated by CEF is essential to sustain nonphotochemical quenching, while an increase in the level of reduced plastoquinone would promote a state transition; both are necessary to down-regulate photosystem II activity. Moreover, stimulation of NDA2-dependent chlororespiration affords additional relief from the elevated reduction state associated with N deprivation through plastid terminal oxidase-dependent water synthesis. Overall, rerouting electrons through the NDA2 catalytic hub in response to photoautotrophic N deprivation sustains cell viability while promoting the dissipation of excess excitation energy through quenching and chlororespiratory processes.

Decreased adiponectin links elevated adipose tissue autophagy with adipocyte endocrine dysfunction in obesity.

BACKGROUND/OBJECTIVES: Adipose tissue (AT) autophagy gene expression is elevated in human obesity, correlating with increased metabolic risk, but mechanistic links between the two remain unclear. Thus, the objective of this study was to assess whether elevated autophagy may cause AT endocrine dysfunction, emphasizing the putative role of adiponectin in fat-liver endocrine communication. SUBJECTS/METHODS: We utilized a large (N=186) human AT biobank to assess clinical associations between human visceral AT autophagy genes, adiponectin and leptin, by multivariate models. A broader view of adipocytokines association with elevated autophagy was assessed using adipocytokine array. Finally, to establish causality, ex vivo studies utilizing a murine AT-hepatocyte cell line co-culture system was used. RESULTS: Circulating high-molecular-weight adiponectin and leptin levels were associated with human omental-AT expression of ATG5 mRNA, associations that remained significant (ß=-0.197, P=0.011; ß=0.267, P<0.001, respectively) in a multivariate model adjusted for age, sex, body mass index and interleukin-6 (IL-6). A similar association was observed with omental-AT LC3A mRNA levels. Bafilomycin-A1 (Baf A) pretreatment of AT explants from high-fat-fed (HFF) mice had no effect on the secretion of some AT-derived endocrine factors, but partially or fully reversed obesity-related changes in secretion of a subset of adipocytokines by >30%, including the obesity-associated upregulation of IL-6, vascular endothelial growth factor, tumor necrosis factor alpha (TNFα) and certain insulin-like growth factor-binding proteins, and the HFF-induced downregulated secretion of IL-10 and adiponectin. Similarly, decreased adiponectin and increased leptin secretion from cultured adipocytes stimulated with TNFα+IL-1ß was partially reversed by small interfering RNA-mediated knockdown of ATG7. AT explants from HFF mice co-cultured with Hepa1c hepatoma cells impaired insulin-induced Akt and GSK3 phosphorylation. This effect was significantly reversed by pretreating explants with Baf A, but not if adiponectin was immunodepleted from the conditioned media. CONCLUSIONS: Reduced secretion of adiponectin may link obesity-associated elevated AT autophagy/lysosomal activity with adipose endocrine dysfunction.

Phenotypic and genetic variation in leptin as determinants of weight regain.

AIMS: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. SUBJECTS AND METHODS: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). RESULTS: Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (ß = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (ß = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (ß = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. CONCLUSION: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.

Mullerian inhibiting substance levels at the time of HCG administration in IVF cycles predict both ovarian reserve and embryo morphology.

BACKGROUND: Pre-antral and early antral follicles secrete Müllerian inhibiting substance (MIS), suggesting that MIS may directly reflect ovarian reserve. Since little is known about how ovarian reserve affects oocyte quality, we attempt here to assess the predictive value of MIS on embryo morphology and IVF outcome. To do so, we measured MIS at the time of HCG administration 36 h prior to oocyte retrieval. METHODS: A total of 257 patients undergoing IVF were prospectively recruited. We measured MIS levels by enzyme-linked immunosorbent assay at the time of HCG, and compared the MIS values to day 3 FSH levels in the prediction of embryo morphology and IVF outcome. RESULTS: The distribution of MIS levels was skewed, with a median of 2.7 ng/ml (range 0 to 28.5 ng/ml). MIS values at the time of HCG administration inversely correlated with basal FSH levels (P = 0.002), and both correlated significantly with patient age, number of mature follicles, number of oocytes retrieved and serum estradiol levels. MIS levels correlated significantly with a greater number of 6-cell embryos and better embryo morphology score, while basal FSH levels did not correlate with these outcome variables. MIS levels > or =2.7 ng/ml portended improved oocyte quality as reflected in a higher implantation rate (P = 0.001) and a trend toward a better clinical pregnancy rate (P = 0.084). CONCLUSIONS: MIS levels seem to predict not only ovarian reserve, but also embryo morphology. Measurement of MIS at the time of HCG administration may, therefore, in the future improve management of patients undergoing treatments with assisted reproductive technology.

Factors associated with low reported energy intake in the elderly.

BACKGROUND: Underreporting of dietary intake can be estimated by the Energy Ratio (ER) between reported energy intake (EI) and calculated total energy expenditure (TEE). The gap between EI and TEE is usually attributed to underreporting. In elderly populations, compromised dietary intake and health status may offer alternative explanations to this gap. OBJECTIVE: This study aimed to characterize "underreporting" of dietary intake and low energy reporters (LER) among the elderly. DESIGN: Participants aged 65 years and over, were recruited using random population sampling of the Negev population. Data were collected using the 24-h recall method with additional demographic and age-specific health questionnaires. ER was calculated using the ratio between reported energy intake and calculated TEE computed by the Schofield formula. LER were defined as those with reported energy intake of less than 0.8 calculated BMR using the Schofield formula. RESULTS: We restricted our analysis to 191 elderly aged 65-74 y and 177 aged 75 y and older who reported their diet to be "as usual." In univariate analyses, BMI < 22, better health status, use of fewer than four medications and good reported appetite were significantly related to higher ER. No difference was shown in ER by gender, level of education, and family status. Weight loss superior 5 kg was associated with low ER (p = 0.049). In a linear regression model, low ER (indicating "underreporting") was significantly associated with higher activity level and use of over four medications. Using a dichotomous approach, Low Energy Reporters (LER) used a higher number of medications, ate fewer food items per day and suffered from poorer appetite. CONCLUSIONS: In the elderly, ER < 1 may indicate underreporting in dietary intake, and indeed, is frequent among the obese. Nonetheless, among the elderly, ER < 1 may reflect truly low caloric intake. Our results suggest that, to some degree, health status variables are associated with decreased ER, supporting a true caloric deprivation state.

A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes.

AIMS: We examined the association between lipoprotein (Lp)(a) and CHD among women with type 2 diabetes. METHODS: Of 32,826 women from the Nurses' Health Study who provided blood at baseline, we followed 921 who had a confirmed diagnosis of type 2 diabetes. RESULTS: During 10 years of follow-up (6,835 person-years), we documented 122 incident cases of CHD. After adjustment for age, smoking, BMI, glycosylated HbA(1)c, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other cardiovascular risk factors, the relative risk (RR) comparing extreme quintiles of Lp(a) was 1.95 (95% CI 1.07-3.56). The association was not appreciably altered after further adjustment for apolipoprotein B(100) or several inflammatory biomarkers. Increasing levels of Lp(a) were associated with lower levels of TGs. The probability of developing CHD over 10 years was higher among diabetic women with substantially higher levels of both Lp(a) (>1.07 micromol/l) and TGs (>2.26 mmol/l) than among diabetic women with lower levels (22 vs 10%, p log-rank test=0.049). Diabetic women with a higher level of only Lp(a) or TGs had a similar (14%) risk. In a multivariate model, diabetic women with higher levels of Lp(a) and TGs had an RR of 2.46 (95% CI 1.21-5.01) for developing CHD, as compared with those with lower levels of both biomarkers (p for interaction=0.413). The RRs for women with a higher level of either Lp(a) (RR=1.22, 95% CI 0.77-1.92) or TGs (RR=1.39, 95% CI 0.78-2.42) were comparable. CONCLUSIONS/INTERPRETATION: Increased levels of Lp(a) were independently associated with risk of CHD among diabetic women.

Moderate alcohol intake and markers of inflammation and endothelial dysfunction among diabetic men.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is characterised by heightened inflammation and endothelial dysfunction. Moderate alcohol intake has been associated with a reduced risk of cardiovascular disease in type 2 diabetic patients. It remains to be determined whether there is an association between alcohol and inflammation in individuals with diabetes. METHODS: We investigated the relationship between alcohol intake and inflammation in 726 of 18,159 men who returned blood samples in the Health Professionals Follow-up Study and had confirmed type 2 diabetes at blood draw. RESULTS: In age-adjusted analyses, alcohol intake was associated with lower levels of HbA1c, fibrinogen, soluble tumour necrosis factor receptor-2 (sTNF-R2) and soluble vascular adhesion molecule-1 (sVCAM-1), and with higher levels of HDL cholesterol and adiponectin (p value for trends <0.05). After adjustment for age, HbA1c, insulin use, fasting status, smoking, BMI, physical activity, aspirin use, prevalence of cardiovascular disease and dietary factors, each additional drink per day was related to increased HDL cholesterol (0.053 mmol/l, p<0.0001) and adiponectin (0.8 microg/ml, p=0.01), and decreased sTNFR-2 (73 pg/ml, p=0.03), fibrinogen (0.302 micromol/l, p=0.02) and sVCAM-1 (33 ng/ml, p=0.02). The relationship between alcohol and inflammatory biomarkers persisted when subjects were stratified according to HbA1c levels. CONCLUSIONS/INTERPRETATION: Moderate alcohol intake may have a beneficial effect on markers of inflammation and endothelial dysfunction in type 2 diabetic patients.

Joint role of non-HDL cholesterol and glycated haemoglobin in predicting future coronary heart disease events among women with type 2 diabetes.

AIMS/HYPOTHESIS: Non-HDL cholesterol (the sum of LDL, VLDL and IDL cholesterol) is considered to be particularly valuable in the management of dyslipidaemia in type 2 diabetes. However, it remains uncertain whether the association between non-HDL cholesterol and cardiovascular risk in type 2 diabetes depends on the status of hyperglycaemia. We aimed to determine whether non-HDL cholesterol predicts CHD events among diabetic women independently of currently established risk factors and the status of glycaemic control. METHODS: We prospectively followed 921 diabetic women in the Nurses' Health Study, who were free of cardiovascular disease at the time that blood was drawn in 1989/90. During 10 years of follow-up, we identified 122 incident CHD cases. RESULTS: After adjustment for age, BMI, smoking, alcohol consumption, and other lifestyle risk factors, the multivariate relative risks (RRs) of CHD for extreme quartiles were 1.97 (95% CI: 1.14-3.43) for non-HDL cholesterol, 1.78 (1.02-3.11) for apolipoprotein B-100, and 1.93 (1.15-3.22) for LDL cholesterol. However, the association between non-HDL cholesterol and CHD risk was only apparent among women with elevated fasting triglycerides (RR for extreme quartiles: 3.80; p=0.045). HbA(1)c was strongly associated with increased CHD risk (RR for increase by 1 unit: 1.24; 95% CI: 1.13-1.35), and both non-HDL cholesterol and HbA(1)c additively predicted CHD risk (RR for the combination of high non-HDL cholesterol and high HbA(1)c [tertiles]: 4.59). CONCLUSIONS/INTERPRETATION: Our study suggests that non-HDL cholesterol and HbA(1)c are potent predictors of CHD risk in diabetic women. Therapies to lower CHD risk in diabetic patients should emphasise both glycaemic control and lipid lowering.

Lack of association between breast artery calcification seen on mammography and coronary artery disease on angiography.

OBJECTIVES: Some studies have found correlations between the presence of breast artery calcium (BAC) observed on routine mammograms and risk factors for coronary artery disease (CAD). The aim of this study was to investigate whether such calcifications could predict the presence of coronary atherosclerosis. METHODS: A total of 319 female patients between 50 and 70 years of age, 187 with significant CAD and 132 with angiographically normal coronary arteries, were randomly selected from a computerised database of our central catheterisation laboratory. The patients' mammograms were evaluated independently for the presence of BAC in a blinded fashion by an experienced breast radiologist, and additional clinical data were extracted from clinical charts. RESULTS: The women in the CAD group were older (62.5 vs 60.7 years, p=0.05) and had a higher prevalence of hypertension, diabetes mellitus and dyslipidaemia. Although the prevalence of BAC was marginally higher in the CAD group (43.9% vs 37.1%, p=0.138), this tendency was eliminated after controlling for confounders. Multiple regression analyses indicated that only age above 63 years (odds ratio [OR]=3.0, 95% confidence interval [CI]=1.8-4.9) and hypertension (OR=2.2, 95% CI=1.2-4.1), but not angiographic evidence of CAD (OR=1.0, 95% CI=0.6-1.6), predict with BAC on mammography. CONCLUSIONS: Despite correlation with some risk factors for CAD, the presence of BAC does not differentiate between patients with angiographic evidence of CAD and those with angiographically normal coronary arteries.

[Prevalence and characteristics of myocardial infarction, diabetes and hypertension in the adult Jewish population: results from the Negev Nutritional Study].

BACKGROUND: Monitoring the prevalence of chronic conditions such as chronic heart disease, diabetes and hypertension in adult populations is essential for health services planning and identification of populations at high risk. OBJECTIVES: To describe the prevalence of self-reported conditions such as myocardial infarction, diabetes mellitus and hypertension in the Jewish Negev population and the patterns of use of health services and dietary behavior of persons suffering from these conditions. METHODS: A random proportional geographic cluster sample of the adult Jewish population (n = 1159, age 35+) from the Negev area was interviewed at home between 1998 and 1999. The interview included questions regarding chronic conditions, patterns of health services use and dietary behavior. RESULTS: Men had twice the prevalence of myocardial infarction and underwent more invasive cardiac procedures than women. The highest prevalence of myocardial infarction and hypertension were found in Central- and Eastern European-born persons while the highest prevalence of diabetes was found in Western-born participants. Of the participants < 61 years of age, 19% reporting diabetes and 33% reporting hypertension did not use medication and were not adhering to an appropriate diet. Thus, one-third of those with reported hypertension and 15% of those reported as diabetics were not adhering to any treatment. The prevalence reported in this study was higher than the national data. CONCLUSIONS: The data collected showed a higher prevalence of chronic diseases among the southern Israeli population as compared with the national data. Among people with chronic diseases, high percentages are not treated. The information reported here may help in the allocation of health services for the south of Israel and in the identification of populations at risk.

Dietary intake and eating patterns of elderly people in Israel: who is at nutritional risk?

OBJECTIVE: To determine dietary intake and eating patterns of older persons in Israel and to identify factors associated with low intake. DESIGN: A cross-sectional study. SETTING: Community-dwelling participants living in the Beer-Sheva area were interviewed at home, using a 24 h food questionnaire with additional questions regarding health and eating habits. Dietary intake was compared between people aged 65-74 and 75 y and older. SUBJECTS: A total of 377 people over the age of 65 224 aged 65-74 and 153>75, were randomly selected from the Negev population. RESULTS: Dietary intake of energy, fat, carbohydrates, vitamins E, C and B(1) were significantly lower for people aged 75 and older compared with people aged 65-74. Low energy intake was associated with lower subjective health status for men (P<0.01), poor appetite (P<0.01) and more gastrointestinal problems (P<0.05) for women and lower snack consumption (P<0.01) for both genders. In a multivariate model, low energy intake was associated with low appetite and higher use of medication for both sexes and with frequency of eating alone and not consuming snacks for men. CONCLUSIONS: Dietary intake is lower among individuals older than 75 than in 65-74 y old. Risk factors for low intake include poor appetite and health status, gastrointestinal problems, and eating alone. Snacking enhanced dietary intake and should be encouraged in this group.

Attitudes of physicians and medical students toward nutrition's place in patient care and education at Ben-Gurion University.

OBJECTIVES: To describe attitudes of physicians and medical students at one medical school toward the role of dietetic treatment in patient care and toward adding nutritional education into the medical school curriculum. STUDY DESCRIPTION: A cross sectional survey was conducted at Soroka University Medical Center and Ben-Gurion University's School of Medicine. The attitudes of 67 physicians and 62 medical students toward nutritional treatment were determined using an attitudes questionnaire. RESULTS: Despite recommendations in medical treatment protocols to use dietary intervention as the primary treatment for several chronic diseases, physicians did not rate nutritional treatment as the most important treatment for these conditions. Students rated the importance of nutritional treatment significantly higher for each of the medical conditions presented than did practicing physicians (p=0.001). Almost 50% of the physicians reported not using nutritional treatment due to lack of time and awareness of the available options. Physicians and students rated the importance of nutrition education in the curriculum equally. Physicians who rated nutrition treatment as important also felt the need to add this subject to the medical education curriculum. CONCLUSION: Physicians and medical students agreed that dietary treatment and nutrition education are important. Our results suggest that there is good reason to introduce nutrition topics into medical school curricula. Improved nutritional knowledge in physicians would improve the teamwork capacity between physicians and dieticians in the realms of curative care and public health.

Dietary treatment of hypercholesterolemia: do dietitians do it better? A randomized, controlled trial.

PURPOSE: Current guidelines of the National Cholesterol Education Program (NCEP) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic. We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians. SUBJECTS AND METHODS: Hypercholesterolemic patients detected during a cholesterol screening project were randomly assigned to receive dietary counseling by a physician only (70 patients) or by a physician and a registered dietitian (66 patients). Patients were observed for 1 year to determine compliance with NCEP guidelines. RESULTS: At 3 months, the mean (+/- SD) decrease in the serum low-density lipoprotein (LDL) cholesterol level was 7% +/- 11% in the physician group and 12% +/- 10% in the dietitian group (P <0.004). A decrease of 10% or more in the LDL cholesterol level was seen in 25 patients (36%) in the physician group and 43 patients (65%) in the dietitian group (P <0.001). Only 40 (29%) of the patients in both groups achieved their NCEP target goals at 3 months. The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months, both groups lost about half of the beneficial effects on LDL cholesterol levels, and the difference between the two groups diminished. CONCLUSIONS: The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians. However, long-term compliance remains inadequate. For patients at high risk, consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications.

Negev nutritional studies: nutritional deficiencies in young and elderly populations.

The importance of nutrition to public health and preventive medicine is evident. Undernutrition is a main nutritional risk factor in the elderly and has been established as a cause of excess morbidity and mortality in different segments of the older population. In the infant population, inadequate nutrition is one of the causes of iron-deficiency anemia, which is associated with impaired physical and cognitive development and lowered immunity. The aim of this paper was to estimate the nutritional pattern and micronutrient deficiencies in elderly and young populations in the Negev. In southern Israel, 351 subjects over 64 years old reported mean dietary intake that was lower than that in younger persons and was independent of the presence of chronic diseases. Current data from southern Israel on healthy Jewish children revealed anemia prevalence of 15% in the second year of life. Data from recent prospective study on Bedouin children showed that anemia affected one quarter of children at age one year. Thus, infants in this area are at high risk for iron deficiency. The findings require the attention of public health authorities and food manufacturers, and should result in a range of activities including publicity and educational programs, fortification of foods, and supplementation programs in high risk-groups.

[Effects of vertical banded gastroplasty on weight, quality of life and nutrition].

We examined the long term results of vertical banded gastroplasty 3-10 years after operation. They were assessed by weight lost, incidence and severity of untoward effects and improvement in diet and in quality of life in 75 of 122 who had had the operation. Average weight lost was 28.5 +/- 14.9 kg (p < 0.001) in 5 years and 58.6 +/- 30.4% of excess weight, which brought patients to within 32 +/- 25.2% of ideal weight. According to these measures, in 63-76% the operation had been successful in causing weight loss. The 2 criteria for successful weight loss were loss of more than 50% of weight in excess of ideal body weight and residual body weight less than 50% greater than ideal body weight. There was a greater risk of failure in unmarried subjects older than 45 (odds ratio for not losing weight was 6; in those weighing more than 120 kg it was 9). We saw evidence of this mostly 4 years after operation (odds ratio 11). The degree of success in weight loss was correlated with texture of food (softness) preferred and length of operation. Of those interviewed, only 65% were satisfied with their results. The greatest improvement in quality of life measurements was in physical activity, perception of health, and frequency of feeling depressed. Side-effects were vomiting, reflux and fatigue. Only 34.7% were able to digest solid foods, so that subjects are at risk for nutritional deficiencies.