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Title:
External review and validation of the Swedish national inpatient register
Authors:
Ludvigsson, Jonas F.; Andersson, Eva; Ekbom, Anders; Feychting, Maria; Kim, Jeong-Lim; Reuterwall, Christina; Heurgren, Mona; Olausson, Petra Otterblad
Abstract:
BACKGROUND: The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. METHODS AND RESULTS: In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. CONCLUSIONS: In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
Published:
June 8, 2011
Title:
Diet of Paranthropus boisei in the Early Pleistocene of East Africa
Authors:
Cerling, Thure; Mbua, Emma; Kirera, Francis; Manthi, Fredrick; Grine, Frederick; Leakey, Meave; Sponheimer, Matt; Uno, Kevin
Abstract:
The East African hominin Paranthropus boisei was characterized by a suite of craniodental features that have been widely interpreted as adaptations to a diet that consisted of hard objects that required powerful peak masticatory loads. These morphological adaptations represent the culmination of an evolutionary trend that began in earlier taxa such as Australopithecus afarensis, and presumably facilitated utilization of open habitats in the Plio-Pleistocene. Here, we use stable isotopes to show that P. boisei had a diet that was dominated by C(4) biomass such as grasses or sedges. Its diet included more C(4) biomass than any other hominin studied to date, including its congener Paranthropus robustus from South Africa. These results, coupled with recent evidence from dental microwear, may indicate that the remarkable craniodental morphology of this taxon represents an adaptation for processing large quantities of low-quality vegetation rather than hard objects.
Published:
June 6, 2011
Title:
Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?
Authors:
Fohl, Alexander L; Regal, Randolph E
Abstract:
Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach’s “acid mantle” against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H+/K+-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H2RAs should be used as the preferred agents over PPIs.
Published:
June 5, 2011
Title:
Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies
Authors:
Chan, Doris S. M.; Lau, Rosa; Aune, Dagfinn; Vieira, Rui; Greenwood, Darren C.; Kampman, Ellen; Norat, Teresa
Abstract:
Background The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. Methods and Findings Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR for 100 g/day increase = 1.17, 95% CI = 1.05−1.31) and processed meat (RR for 50 g/day increase = 1.18, 95% CI = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. Conclusions High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.
Published:
June 5, 2011
Title:
Hypermethylation of tumor-related genes in Tunisian patients with gastric carcinoma: clinical and biological significance
Authors:
Ben Ayed-Guerfali, Dorra; Benhaj, Khemais; Khabir, Abdelmajid; Abid, Mohamed; Bayrouti, Mohamed Issam; Sellami-Boudawara, Tahia; Gargouri, Ali; Mokdad-Gargouri, Raja
Abstract:
BACKGROUND: Promoter hypermethylation is an alternative mechanism of gene silencing in cancers including gastric carcinoma (GC). Its affects genes with crucial functions as tumor suppressor. METHODS: DNA methylation in the promoter of P16INK4a, DAPK, retinoic acid receptor β (RARβ2), RASSF1A, and CDH1 genes was investigated in 79 Tunisian patients with GC using methylation-specific PCR. RESULTS: The methylation frequencies vary from 31.6% for P16INK4a to 65.8% for RARβ2. Hypermethylation of DAPK and CDH1 was associated with tumor grade and age (P = 0.04 and 0.034) respectively, while hypermethylation of RASSF1A correlated with TNM stage (P = 0.027). The distribution of the methylated DNA at P16INK4a, DAPK, and CDH1 promoters were different in the intestinal and diffuse histotypes of GC according to TNM. Moreover, the survival rate of patients with P16INK4a methylated status was shorter than that of patients with the unmethylated status (P log rank = 0.009). On the other hand, the hypermethylation of RARβ2 correlated with COX-2 expression (P = 0.001). CONCLUSION: We showed that methylation of P16INK4a is predictive of poor prognosis and could be a useful marker. Moreover, the association between RARβ2 methylation and COX-2 expression suggests a functional link between these two proteins in gastric carcinogenesis.
Published:
May 31, 2011
Title:
Metabolic management of brain cancer
Authors:
Seyfried, Thomas N.; Kiebish, Michael A.; Marsh, Jeremy; Shelton, Laura M.; Huysentruyt, Leanne C.; Mukherjee, Purna
Abstract:
Malignant brain tumors are a significant health problem in children and adults. Conventional therapeutic approaches have been largely unsuccessful in providing long-term management. As primarily a metabolic disease, malignant brain cancer can be managed through changes in metabolic environment. In contrast to normal neurons and glia, which readily transition to ketone bodies (β-hydroxybutyrate) for energy under reduced glucose, malignant brain tumors are strongly dependent on glycolysis for energy. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome and normal mitochondria can effectively transition from one energy state to another. Mutations restrict genomic and metabolic flexibility thus making tumor cells more vulnerable to energy stress than normal cells. We propose an alternative approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and metabolically challenged tumor cells. This approach to brain cancer management is supported from recent studies in mice and humans treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are presented for the metabolic management of brain cancer. This article is part of a Special Issue entitled: Bioenergetics of Cancer.
Published:
May 31, 2011
Title:
Serum starvation: caveat emptor
Authors:
Pirkmajer, Sergej; Chibalin, Alexander V.
Abstract:
Serum starvation is one of the most frequently performed procedures in molecular biology and there are literally thousands of research papers reporting its use. In fact, this method has become so ingrained in certain areas of research that reports often simply state that cells were serum starved without providing any factual details as to how the procedure was carried out. Even so, we quite obviously lack unequivocal terminology, standard protocols, and perhaps most surprisingly, a common conceptual basis when performing serum starvation. Such inconsistencies not only hinder interstudy comparability but can lead to opposing and inconsistent experimental results. Although it is frequently assumed that serum starvation reduces basal activity of cells, available experimental data do not entirely support this notion. To address this important issue, we studied primary human myotubes, rat L6 myotubes and human embryonic kidney (HEK)293 cells under different serum starvation conditions and followed time-dependent changes in important signaling pathways such as the extracellular signal-regulated kinase 1/2, the AMP-activated protein kinase, and the mammalian target of rapamycin. Serum starvation induced a swift and dynamic response, which displayed obvious qualitative and quantitative differences across different cell types and experimental conditions despite certain unifying features. There was no uniform reduction in basal signaling activity. Serum starvation clearly represents a major event that triggers a plethora of divergent responses and has therefore great potential to interfere with the experimental results and affect subsequent conclusions.
Published:
May 24, 2011
Title:
Diabetes and breast cancer among women with BRCA1 and BRCA2 mutations
Authors:
Bordeleau, Louise; Lipscombe, Lorraine; Lubinski, Jan; Ghadirian, Parviz; Foulkes, William D.; Neuhausen, Susan; Ainsworth, Peter; Pollak, Michael; Sun, Ping; Narod, Steven A.; the Hereditary Breast Cancer Clinical Study Group
Abstract:
BACKGROUND—Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. METHODS—The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self-report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer. RESULTS—There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15-year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4–2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) >25.0 kg/m2 (odds ratio, 5.8; 95% CI, 4.0–8.6; P = .0001). CONCLUSIONS—After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2-fold increase in the risk of diabetes, which is exacerbated by a high BMI.
Published:
April 30, 2011
Title:
The Twin Epidemics of Poverty and Diabetes: Understanding Diabetes Disparities in a Low-Income Latino and Immigrant Neighborhood
Authors:
Chaufan, Claudia; Davis, Meagan; Constantino, Sophia
Abstract:
In the United States, low-income immigrant groups experience greater health disparities and worse health-related outcomes than Whites, including but not limited to higher rates of type 2 diabetes (T2DM). The prevention and adequate management of T2DM are, to a great extent, contingent on access to healthy food environments. This exploratory study examines “upstream” antecedent factors contributing to “downstream” health disparities, with a focus on disparities in the structural sources of T2DM risk, especially food environments. Our target group is Latino immigrants receiving services from a non-profit organization (NGO) in Northern California. Methods are mixed and data include focus groups and surveys of our target group, interviews to NGO staff members, and estimation of the thrifty food market basket in local grocery stores. We find that while participants identify T2DM as the greatest health problem in the community, access to healthy foods is severely restricted, geographically, culturally, and economically, with 100% of participants relying on formal or informal food assistance and local food stores offering limited variety of healthy foods and at unaffordable prices. While this article is empirical, its goal is primarily conceptual—to integrate empirical findings with the growing literature underscoring the sociopolitical context of the social determinants of health in general and of T2DM disparities in particular. We propose that interventions to reduce T2DM and comparable health disparities must incorporate a social justice perspective that guarantees a right to adequate food and other health-relevant environments, and concomitantly, a right to health.
Published:
April 30, 2011
Title:
Reversal of Diabetic Nephropathy by a Ketogenic Diet
Authors:
Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.
Abstract:
Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.
Published:
April 19, 2011
Title:
Genomic signatures of diet-related shifts during human origins
Authors:
Babbitt, Courtney C.; Warner, Lisa R.; Fedrigo, Olivier; Wall, Christine E.; Wray, Gregory A.
Abstract:
There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates.
Published:
April 6, 2011
Title:
Evolution of gustatory perceptions
Authors:
Pasquet, Patrick; Hladik, Annette; Tarnaud, Laurent
Abstract:
Published:
March 31, 2011
Title:
Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971–2006
Authors:
Austin, Gregory L.; Ogden, Lorraine G.; Hill, James O.
Abstract:
ABSTRACT. Background: The prevalence of obesity in the United States has increased dramatically.Objective: The aim of this study was to determine trends in car
Published:
March 31, 2011
Title:
Growth Hormone plus Childhood Low-Dose Estrogen in Turner's Syndrome
Authors:
Ross, Judith L.; Quigley, Charmian A.; Cao, Dachuang; Feuillan, Penelope; Kowal, Karen; Chipman, John J.; Cutler, Gordon B.
Abstract:
BACKGROUND Short stature and ovarian failure are characteristic features of Turner’s syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner’s syndrome. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone–estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. RESULTS The mean standard-deviation scores for adult height, attained at an average age of 17.0±1.0 years, after an average study period of 7.2±2.5 years were −2.81±0.85, −3.39±0.74, −2.29±1.10, and −2.10±1.02 for the double-placebo, estrogen-alone, growth hormone–alone, and growth hormone–estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78±0.13 increase in the height standard-deviation score (5.0 cm) (P
Published:
March 30, 2011
Title:
Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory
Authors:
Shrestha, Binu; Reed, J. Michael; Starks, Philip T.; Kaufman, Gretchen E.; Goldstone, Jared V.; Roelke, Melody E.; O'Brien, Stephen J.; Koepfli, Klaus-Peter; Frank, Laurence G.; Court, Michael H.
Abstract:
The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea) and northern elephant seal (Mirounga angustirostris) showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter). Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0) as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora.
Published:
March 27, 2011
Title:
Foraging and farming as niche construction: stable and unstable adaptations
Authors:
Rowley-Conwy, Peter; Layton, Robert
Abstract:
All forager (or hunter–gatherer) societies construct niches, many of them actively by the concentration of wild plants into useful stands, small-scale cultivation, burning of natural vegetation to encourage useful species, and various forms of hunting, collectively termed ‘low-level food production’. Many such niches are stable and can continue indefinitely, because forager populations are usually stable. Some are unstable, but these usually transform into other foraging niches, not geographically expansive farming niches. The Epipalaeolithic (final hunter–gatherer) niche in the Near East was complex but stable, with a relatively high population density, until destabilized by an abrupt climatic change. The niche was unintentionally transformed into an agricultural one, due to chance genetic and behavioural attributes of some wild plant and animal species. The agricultural niche could be exported with modifications over much of the Old World. This was driven by massive population increase and had huge impacts on local people, animals and plants wherever the farming niche was carried. Farming niches in some areas may temporarily come close to stability, but the history of the last 11 000 years does not suggest that agriculture is an effective strategy for achieving demographic and political stability in the world's farming populations.
Published:
March 26, 2011
Title:
Hallmarks of cancer: the next generation
Authors:
Hanahan, Douglas; Weinberg, Robert A.
Abstract:
The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Published:
March 3, 2011
Title:
Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia
Authors:
Rosenheck, Robert A.; Krystal, John H.; Lew, Robert; Barnett, Paul G.; Fiore, Louis; Valley, Danielle; Thwin, Soe Soe; Vertrees, Julia E.; Liang, Matthew H.
Abstract:
Background Long-acting injectable risperidone, a second-generation antipsychotic agent, may improve adherence to treatment and outcomes in schizophrenia, but it has not been tested in a long-term randomized trial involving patients with unstable disease. Methods We randomly assigned patients in the Veterans Affairs (VA) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of longacting injectable risperidone every two weeks or to a psychiatrist’s choice of an oral antipsychotic. All patients were followed for up to 2 years. The primary end point was hospitalization in a VA or non-VA psychiatric hospital. Symptoms, quality of life, and functioning were assessed in blinded videoconference interviews. Results Of 369 participants, 40% were hospitalized at randomization, 55% were hospitalized within the previous 2 years, and 5% were at risk for hospitalization. The rate of hospitalization after randomization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics (39% after 10.8 months vs. 45% after 11.3 months; hazard ratio, 0.87; 95% confidence interval, 0.63 to 1.20). Psychiatric symptoms, quality of life, scores on the Personal and Social Performance scale of global functioning, and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments. Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms. Conclusions Long-acting injectable risperidone was not superior to a psychiatrist’s choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization, and it was associated with more local injection-site and extrapyramidal adverse effects. (Supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs; ClinicalTrials.gov number, NCT00132314.)
Published:
March 2, 2011
Title:
RAGE: The Beneficial and Deleterious Effects by Diverse Mechanisms of Actions
Authors:
Han, Sun-Ho; Kim, Yoon Hee; Mook-Jung, Inhee
Abstract:
Receptor for advanced glycation endproducts (RAGE) is a transmembrane protein that belongs to the immunoglobu-lin superfamily. RAGE is expressed ubiquitously-high in lung and moderate to low in a wide range of cells-in a tightly regulated manner at various stages of development. RAGE is a pattern recognition receptor that binds to multi-ple ligands, including amphoterin, members of the S100/ calgranulin family, the integrin Mac-1, and amyloid β-pep-tide (Aβ). RAGE-ligand engagement effects the activation of diverse cascades that initiate and stimulate chronic stress pathways and repair, depending on the ligand, envi-ronment, and developmental stage. Further, RAGE-ligand interaction and the consequent upregulation of RAGE through a positive feedback loop are often associated with various diseases, including vascular disease, diabetes, cancer, and neurodegenerative disease. It is unknown how RAGE mediates these events, but such phenomena ap-pear to be linked to the inflammatory response. In this review, we summarize the findings on RAGE from pub-lished reports and ongoing studies. Also, the implication of RAGE in Alzheimer disease, the most common neuro-degenerative disease in the elderly population, will be dis-cussed, with a focus on Aβ-RAGE interactions with regard to signaling pathways and their impact on cellular activity.
Published:
February 27, 2011
Title:
HEALTHY DIETS AND SCIENCE: Evidence of Human Adaptation to Increased Carnivory
Authors:
Evans, David
Abstract:
Published:
February 4, 2011
Title:
Diabetes Prevalence by Length of Residence Among US Immigrants
Authors:
Oza-Frank, Reena; Stephenson, Rob; Venkat Narayan, K. M.
Abstract:
Although at arrival, US immigrants have a lower prevalence of overweight compared to native born individuals, prevalence increases with increased length of residence. It is unknown whether length of residence similarly affects diabetes. Data on adults aged 18–74 years from the National Health Interview Survey were pooled from 1997 to 2005 (n = 33,499). Diabetes prevalence by length of residence was estimated by multivariable logistic regression. Diabetes prevalence was higher with increased length of residence in the US, independent of age and body mass index (<5 years residence: 3.3%; 5–<10 year, 3.4%; 10–<15 year, 4.5%; 15+ year, 5.3%; P for trend <0.001). Length of residence had the largest effect on diabetes prevalence among immigrants who arrive at 25–44 years of age (prevalence: 1.4% for
Published:
January 31, 2011
Title:
Prostate-Derived ETS Factor Regulates Epithelial-to-Mesenchymal Transition through Both SLUG-Dependent and Independent Mechanisms
Authors:
Findlay, V. J.; Turner, D. P.; Yordy, J. S.; McCarragher, B.; Shriver, M. R.; Szalai, G.; Watson, P. M.; LaRue, A. C.; Moussa, O.; Watson, D. K.
Abstract:
The 5-year survival rate is very low when breast cancer becomes metastatic. The metastatic process is governed by a network of molecules of which SLUG is known to play a major role as a regulator of epithelial-to-mesenchymal transition (EMT). Prostate-derived ETS factor (PDEF) has been proposed as a tumor suppressor, possibly through inhibition of invasion and metastasis; therefore, understanding the mechanism of PDEF regulation may help to better understand its role in breast cancer progression.This study shows for the first time that the transcription factor SLUG is a direct target of PDEF in breast cancer. We show that the expression of PDEF is able to suppress/dampen EMT through the negative regulation of SLUG. In addition, we show that PDEF is also able to regulate downstream targets of SLUG, namely E-cadherin, in both SLUG-dependent and -independent manners, suggesting a critical role for PDEF in regulating EMT.
Published:
January 31, 2011
Title:
Diet and Brain Evolution: Nutritional Implications of Large Human Brain Size
Authors:
Leonard, William; Snodgrass, Josh; Robertson, Marcia
Abstract:
Summary Points on Diet and Human Brain Evolution: • Humans expend a much larger share of their resting energy budget on brain metabolism than other species. Adult humans spend 20–25% of the RMR on the brain, as compared to 8–10% in other primates, and 3–5% in non-primate mammals. • To support the high energy costs of brain metabolism, humans consume diets that are easier to digest and much more dense in energy and fat than other primate species. • The first major increase in brain size in the human lineage occurred with the evolution of the genus Homo at 2.0–1.7 million years ago. During this time, we also have evidence from the fossil and archaeological record for greater consumption of animal foods. This increased dietary quality was likely important for supporting brain evolution. • The addition of animal foods to the diet of early Homo would also have increased the availability of key long-chain polyunsaturated fatty acids that are essential for brain growth and development: DHA and AA. • For human infants, the energy costs of brain metabolism are extraordinarily high (
Published:
January 30, 2011
Title:
First identification of dimethoxycinnamic acids in human plasma after coffee intake by liquid chromatography-mass spectrometry
Authors:
Nagy, Kornél; Redeuil, Karine; Williamson, Gary; Rezzi, Serge; Dionisi, Fabiola; Longet, Karin; Destaillats, Frédéric; Renouf, Mathieu
Abstract:
There is a substantial amount of published literature on the bioavailability of various coffee components including the most abundant metabolites, caffeic and ferulic acids. Surprisingly, to date, the appearance of dimethoxycinnamic acid derivatives in humans has not been reported despite the fact that methylated form of catechol-type polyphenols could help maintain, modify or even improve their biological activities. This study reports an LC-MS method for the detection of dimethoxycinnamic acid in human plasma after treatment with an esterase. Liquid chromatography, including the combination of methanol and acetonitrile as organic eluent, was optimized to resolve all interferences and enable reliable detection and identification of 3,4-dimethoxycinnamic and 3,4-dimethoxy-dihydrocinnamic acids. In addition to the good mass accuracy achieved (better than 5 ppm), tandem mass spectrometric and co-chromatography experiments further confirmed the identity of the compounds. The optimized method was applied to analyze samples obtained immediately, 1 and 10 h after coffee ingestion. The results show that in particular 3,4-dimethoxycinnamic acid appears in high abundance (∼380 nM at 60 min) in plasma upon coffee intake, indicating that it is important to consider these derivatives in future bioavailability and bioefficacy studies.
Published:
January 20, 2011
Title:
Complementary feeding: a Global Network cluster randomized controlled trial
Authors:
Krebs, Nancy F.; Hambidge, K. Michael; Mazariegos, Manolo; Westcott, Jamie; Goco, Norman; Wright, Linda L.; Koso-Thomas, Marion; Tshefu, Antoinette; Bose, Carl; Pasha, Omrana; Goldenberg, Robert; Chomba, Elwyn; Carlo, Waldemar; Kindem, Mark; Das, Abhik; Hartwell, Ty; McClure, Elizabeth; Complementary Feeding Study Group
Abstract:
BACKGROUND: Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. METHODS/DESIGN: A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. DISCUSSION: Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children. TRIAL REGISTRATION: NCT01084109.
Published:
January 12, 2011
Title:
Wild Game Meat: Health Benefits
Authors:
Leanne Vogel
Abstract:
Published:
January 4, 2011
Title:
And thanks for asking!: some answers to "What makes us human?" from biological anthropology.
Authors:
Calcagno, James; Campbell, Benjamin
Abstract:
Published:
December 31, 2010
Title:
Mesolithische teerproductie in Hattemerbroek
Authors:
Kubiak-Martens, Lucy; Kooistra, L.I.; Langer, J.J.
Abstract:
Published:
December 31, 2010
Title:
“So We Adapt Step by Step”: Acculturation experiences affecting diabetes management and perceived health for Chinese American immigrants
Authors:
Chun, Kevin M.; Chesla, Catherine A.; Kwan, Christine M. L.
Abstract:
This study examines how acculturation affects type 2 diabetes management and perceived health for Chinese American immigrants in the U.S. Acculturation experiences or cultural adaptation experiences affecting diabetes management and health were solicited from an informant group of immigrant patients and their spouses (N = 40) during group, couple and individual interviews conducted from 2005 to 2008. A separate respondent group of immigrant patients and their spouses (N = 19) meeting inclusion criteria reviewed and confirmed themes generated by the informant group. Using interpretive phenomenology, three key themes in patients’ and spouses’ acculturation experiences were identified: a) utilizing health care, b) maintaining family relations and roles, and c) establishing community ties and groundedness in the U.S. Acculturation experiences reflecting these themes were broad in scope and not fully captured by current self-report and proxy acculturation measures. In the current study, shifting family roles and evaluations of diabetes care and physical environment in the U.S. significantly affected diabetes management and health, yet are overlooked in acculturation and health investigations. Furthermore, the salience and impact of specific acculturation experiences respective to diabetes management and perceived health varied across participants due to individual, family, developmental, and environmental factors. In regards to salience, maintaining filial and interdependent family relations in the U.S. was of particular concern for older participants and coping with inadequate health insurance in the U.S. was especially distressing for self-described lower-middle to middle-class participants. In terms of impact, family separation and relocating to ethnically similar neighborhoods in the U.S. differentially affected diabetes management and health due to participants’ varied family relations and pre-migration family support levels and diverse cultural and linguistic backgrounds, respectively. Implications for expanding current conceptualizations and measures of acculturation to better comprehend its dynamic and multidimensional properties and complex effects on health are discussed. Additionally, implications for developing culturally-appropriate diabetes management recommendations for Chinese immigrants and their families are outlined.
Published:
December 31, 2010
Title:
The 1.5 Å Crystal Structure of Human Receptor for Advanced Glycation Endproducts (RAGE) Ectodomains Reveals Unique Features Determining Ligand Binding
Authors:
Park, HaJeung; Boyington, Jeffrey C.
Abstract:
Interaction of the pattern recognition receptor, RAGE with key ligands such as advanced glycation end products (AGE), S100 proteins, amyloid β, and HMGB1 has been linked to diabetic complications, inflammatory and neurodegenerative disorders, and cancer. To help answer the question of how a single receptor can recognize and respond to a diverse set of ligands we have investigated the structure and binding properties of the first two extracellular domains of human RAGE, which are implicated in various ligand binding and subsequent signaling events. The 1.5-Å crystal structure reveals an elongated molecule with a large basic patch and a large hydrophobic patch, both highly conserved. Isothermal titration calorimetry (ITC) and deletion experiments indicate S100B recognition by RAGE is an entropically driven process involving hydrophobic interaction that is dependent on Ca2+ and on residues in the C′D loop (residues 54–67) of domain 1. In contrast, competition experiments using gel shift assays suggest that RAGE interaction with AGE is driven by the recognition of negative charges on AGE-proteins. We also demonstrate that RAGE can bind to dsDNA and dsRNA. These findings reveal versatile structural features of RAGE that help explain its ability to recognize of multiple ligands.
Published:
December 23, 2010
Title:
Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles
Authors:
Waterland, Robert A.; Kellermayer, Richard; Laritsky, Eleonora; Rayco-Solon, Pura; Harris, R. Alan; Travisano, Michael; Zhang, Wenjuan; Torskaya, Maria S.; Zhang, Jiexin; Shen, Lanlan; Manary, Mark J.; Prentice, Andrew M.
Abstract:
Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease.
Published:
December 22, 2010
Title:
Metabolomic approach to the nutraceutical effect of rosemary extract plus Ω-3 PUFAs in diabetic children with capillary electrophoresis
Authors:
Balderas, Claudia; Villaseñor, Alma; García, Antonia; Rupérez, F. Javier; Ibañez, Elena; Señorans, Javier; Guerrero-Fernández, Julio; González-Casado, Isabel; Gracia-Bouthelier, Ricardo; Barbas, Coral
Abstract:
Type 1 diabetes mellitus is a major endocrine disorder, affecting approximately 5% of the world's population. It not only leads to hyperglycaemia but also causes many complications, and numerous studies have demonstrated that oxidative stress contributes to these complications. As a new strategy to improve the oxidative damage in diabetes, interest has grown in the usage of natural antioxidants, even more in the long term. Among them, Rosmarinus officinalis (rosemary) has been widely accepted as one of the species with the highest antioxidant activity. In addition, omega-3 polyunsaturated fatty acids were efficient in delaying and decreasing cardiovascular risk factors associated with diabetes. Type 1 diabetic children and the corresponding controls were enrolled in the assay. The aim was evaluating the effect of a special additive containing rosemary extract, vitamin E and PUFAs added to their standard diet through the meat. In the analytical point of view, a metabolomic approach with CE-UV was used to detect possible differences in urine of diabetic children as compared to controls. After the application of the appropriate multivariate statistical tools, clear differences could be observed between treated and non-treated diabetic children and some of the metabolites associated could be identified. This was specially challenging as most of the clinical biochemical parameters measured by target analysis showed no differences between the groups.
Published:
December 14, 2010
Title:
Healthy, Hunger-Free Kids Act
Authors:
Abstract:
Published:
December 12, 2010
Title:
Obama Expected to Sign Child Nutrition Bill
Authors:
Abstract:
Published:
December 12, 2010
Title:
Mexican Americans With Type 2 Diabetes in an Emerging Latino Community: Evaluation of Health Disparity Factors and Interventions
Authors:
Amirehsani, Karen A.
Abstract:
Mexican Americans suffer from disproportionately higher rates of type 2 diabetes and its associated complications than the general population. They also confront significant obstacles to health care access and may not receive the same quality of health care as non-Hispanic Whites. Understanding the factors contributing to their health disparities is critical for nurses and other health care providers working with Latino immigrants, especially those in emerging Latino communities such as North Carolina who may lack the established infrastructure of more traditional Latino communities. The purpose of this article is to explicate these factors and examine culturally competent diabetes interventions being used to assist Mexican Americans increase their knowledge of diabetes and health promoting behaviors in order to achieve better glycemic control and prevent complications.
Published:
November 30, 2010
Title:
Kabloona: Among the Inuit
Authors:
Abstract:
One of my favorite leisure activities is taking long walks at night while listening to audio books. I read a lot of paper books too, but there’s something about walking outdoors with a million star…
Published:
November 22, 2010
Title:
Probabilistic principal component analysis for metabolomic data
Authors:
Nyamundanda, Gift; Brennan, Lorraine; Gormley, Isobel Claire
Abstract:
BACKGROUND: Data from metabolomic studies are typically complex and high-dimensional. Principal component analysis (PCA) is currently the most widely used statistical technique for analyzing metabolomic data. However, PCA is limited by the fact that it is not based on a statistical model. RESULTS: Here, probabilistic principal component analysis (PPCA) which addresses some of the limitations of PCA, is reviewed and extended. A novel extension of PPCA, called probabilistic principal component and covariates analysis (PPCCA), is introduced which provides a flexible approach to jointly model metabolomic data and additional covariate information. The use of a mixture of PPCA models for discovering the number of inherent groups in metabolomic data is demonstrated. The jackknife technique is employed to construct confidence intervals for estimated model parameters throughout. The optimal number of principal components is determined through the use of the Bayesian Information Criterion model selection tool, which is modified to address the high dimensionality of the data. CONCLUSIONS: The methods presented are illustrated through an application to metabolomic data sets. Jointly modeling metabolomic data and covariates was successfully achieved and has the potential to provide deeper insight to the underlying data structure. Examination of confidence intervals for the model parameters, such as loadings, allows for principled and clear interpretation of the underlying data structure. A software package called MetabolAnalyze, freely available through the R statistical software, has been developed to facilitate implementation of the presented methods in the metabolomics field.
Published:
November 22, 2010
Title:
Changes in weight loss, body composition and cardiovascular disease risk after altering macronutrient distributions during a regular exercise program in obese women
Authors:
Kerksick, Chad M.; Wismann-Bunn, Jennifer; Fogt, Donovan; Thomas, Ashli R.; Taylor, Lem; Campbell, Bill I.; Wilborn, Colin D.; Harvey, Travis; Roberts, Mike D.; La Bounty, Paul; Galbreath, Melyn; Marcello, Brandon; Rasmussen, Christopher J.; Kreider, Richard B.
Abstract:
BACKGROUND: This study's purpose investigated the impact of different macronutrient distributions and varying caloric intakes along with regular exercise for metabolic and physiological changes related to weight loss. METHODS: One hundred forty-one sedentary, obese women (38.7 ± 8.0 yrs, 163.3 ± 6.9 cm, 93.2 ± 16.5 kg, 35.0 ± 6.2 kg•m(-2), 44.8 ± 4.2% fat) were randomized to either no diet + no exercise control group (CON) a no diet + exercise control (ND), or one of four diet + exercise groups (high-energy diet [HED], very low carbohydrate, high protein diet [VLCHP], low carbohydrate, moderate protein diet [LCMP] and high carbohydrate, low protein [HCLP]) in addition to beginning a 3x•week(-1) supervised resistance training program. After 0, 1, 10 and 14 weeks, all participants completed testing sessions which included anthropometric, body composition, energy expenditure, fasting blood samples, aerobic and muscular fitness assessments. Data were analyzed using repeated measures ANOVA with an alpha of 0.05 with LSD post-hoc analysis when appropriate. RESULTS: All dieting groups exhibited adequate compliance to their prescribed diet regimen as energy and macronutrient amounts and distributions were close to prescribed amounts. Those groups that followed a diet and exercise program reported significantly greater anthropometric (waist circumference and body mass) and body composition via DXA (fat mass and % fat) changes. Caloric restriction initially reduced energy expenditure, but successfully returned to baseline values after 10 weeks of dieting and exercising. Significant fitness improvements (aerobic capacity and maximal strength) occurred in all exercising groups. No significant changes occurred in lipid panel constituents, but serum insulin and HOMA-IR values decreased in the VLCHP group. Significant reductions in serum leptin occurred in all caloric restriction + exercise groups after 14 weeks, which were unchanged in other non-diet/non-exercise groups. CONCLUSIONS: Overall and over the entire test period, all diet groups which restricted their caloric intake and exercised experienced similar responses to each other. Regular exercise and modest caloric restriction successfully promoted anthropometric and body composition improvements along with various markers of muscular fitness. Significant increases in relative energy expenditure and reductions in circulating leptin were found in response to all exercise and diet groups. Macronutrient distribution may impact circulating levels of insulin and overall ability to improve strength levels in obese women who follow regular exercise.
Published:
November 21, 2010
Title:
Vegetarian diets and public health: biomarker and redox connections
Authors:
Benzie, Iris F. F.; Wachtel-Galor, Sissi
Abstract:
Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.
Published:
November 14, 2010
Title:
A Randomized Controlled Trial of Culturally Tailored Dance and Reducing Screen Time to Prevent Weight Gain in Low-Income African American Girls: Stanford GEMS
Authors:
Robinson, Thomas N.; Matheson, Donna M.; Kraemer, Helena C.; Wilson, Darrell M.; Obarzanek, Eva; Thompson, Nikko S.; Alhassan, Sofiya; Spencer, Tirzah R.; Haydel, K. Farish; Fujimoto, Michelle; Varady, Ann; Killen, Joel D.
Abstract:
Objective
To test a 2-year community- and family-based obesity prevention program for low-income African American girls: Stanford GEMS (Girls' health Enrichment Multi-site Studies).
Design
Randomized controlled trial with follow-up measures scheduled at 6, 12, 18, and 24 months.
Setting
Low-income areas of Oakland, California.
Participants
African American girls aged 8 to 10 years (N=261) and their parents or guardians.
Interventions
Families were randomized to one of two 2-year, culturally tailored interventions: (1) after-school hip-hop, African, and step dance classes and a home/family-based intervention to reduce screen media use or (2) information-based health education.
Main Outcome Measure
Changes in body mass index (BMI).
Results
Changes in BMI did not differ between groups (adjusted mean difference [95% confidence interval] = 0.04 [−0.18 to 0.27] per year). Among secondary outcomes, fasting total cholesterol level (adjusted mean difference, −3.49 [95% confidence interval, −5.28 to −1.70] mg/dL per year), low-density lipoprotein cholesterol level (−3.02 [−4.74 to −1.31] mg/dL per year), incidence of hyperinsulinemia (relative risk, 0.35 [0.13 to 0.93]), and depressive symptoms (−0.21 [−0.42 to −0.001] per year) decreased more among girls in the dance and screen time reduction intervention. In exploratory moderator analysis, the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline (P = .02) and/or those whose parents or guardians were unmarried (P = .01).
Conclusions
A culturally tailored after-school dance and screen time reduction intervention for low-income, preadolescent African American girls did not significantly reduce BMI gain compared with health education but did produce potentially clinically important reductions in lipid levels, hyperinsulinemia, and depressive symptoms. There was also evidence for greater effectiveness in high-risk subgroups of girls.
Trial Registration
clinicaltrials.gov Identifier:NCT00000615
Published:
October 31, 2010
Title:
Holocene climate change in arid Australia from speleothem and alluvial records
Authors:
Quigley, Mark C.; Horton, Travis; Hellstrom, John C.; Cupper, Matthew L.; Sandiford, Mike
Abstract:
New high-resolution MC-ICPMS U/Th ages and C and O isotopic analyses from a Holocene speleothem in arid south-central Australia provide evidence for increased effective precipitation (EP) relative to present at c. 11.5 ka and c. 8—5 ka, peak moisture at 7—6 ka, and onset of an arid climate similar to present by c. 5 ka. δ18O and δ13C time-series data exhibit marked (>+1‰) contemporaneous excursions over base-line values of −5.3‰ and −11.0‰, respectively, suggesting pronounced moisture variability during the early middle Holocene ‘climatic optimum’. Optically stimulated luminescence and 14C ages from nearby terraced aggradational alluvial deposits indicate a paucity of large floods in the Late Pleistocene and at least five large flood events in the last c. 6 kyr, interpreted to mark an increased frequency of extreme rainfall events in the middle Holocene despite overall reduced EP. Increased EP in south-central Australia during the early to middle Holocene resulted from (1) decreased El Niño-Southern Oscillation (ENSO) variability, which reduced the frequency of El Niño-triggered droughts, (2) the prevalence of a more La Niña-like mean climatic state in the tropical Pacific Ocean, which increased available atmospheric moisture, and (3) a southward shift in the Intertropical Convergence Zone (ICTZ), which allowed tropical summer storms associated with the Australian summer monsoon (ASM) to penetrate deeper into the southern part of the continent. The onset of heightened aridity and apparent increase in large flood frequency at c. 5 ka is interpreted to indicate the establishment of an ENSO-like climate in arid Australia in the late Holocene, consistent with a variety of other terrestrial and marine proxies. The broad synchroneity of Holocene climate change across much of the Australian continent with changes in ENSO behavior suggests strong teleconnections amongst ENSO and the other climate systems such as the ASM, Indian Ocean Dipole, and Southern Annular Mode.
Published:
October 31, 2010
Title:
Structural Basis for Ligand Recognition and Activation of RAGE
Authors:
Koch, Michael; Chitayat, Seth; Dattilo, Brian M.; Schiefner, Andre; Diez, Joachim; Chazin, Walter J.; Fritz, Günter
Abstract:
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor involved in inflammatory processes and is associated with diabetic complications, tumor outgrowth, and neurodegenerative disorders. RAGE induces cellular signaling events upon binding of a variety of ligands, such as glycated proteins, amyloid-β, HMGB1, and S100 proteins. The X-ray crystal structure of the VC1 ligand-binding region of the human RAGE ectodomain was determined at 1.85 Å resolution. The VC1 ligand-binding surface was mapped onto the structure from titrations with S100B monitored by heteronuclear NMR spectroscopy. These NMR chemical shift perturbations were used as input for restrained docking calculations to generate a model for the VC1-S100B complex. Together, the arrangement of VC1 molecules in the crystal and complementary biochemical studies suggest a role for self-association in RAGE function. Our results enhance understanding of the functional outcomes of S100 protein binding to RAGE and provide insight into mechanistic models for how the receptor is activated.
Published:
October 12, 2010
Title:
A Systematic Review of the Validity of Dietary Assessment Methods in Children when Compared with the Method of Doubly Labeled Water
Authors:
Burrows, Tracy L.; Martin, Rebecca J.; Collins, Clare E.
Abstract:
Measuring dietary intake in children enables the assessment of nutritional adequacy of individuals and groups and can provide information about nutrients, including energy, food, and eating habits. The aim of this review was to determine which dietary assessment method(s) provide a valid and accurate estimate of energy intake by comparison with the gold standard measure, doubly labeled water (DLW). English-language articles published between 1973 and 2009 and available from common nutrition databases were retrieved. Studies were included if the subjects were children birth to age 18 years and used the DLW technique to validate reported energy intake by any other dietary assessment method. The review identified 15 cross-sectional studies, with a variety of comparative dietary assessment methods. These included a total of 664 children, with the majority having <30 participants. The majority of dietary assessment method validation studies indicated a degree of misreporting, with only eight studies identifying this to a significant level (P
Published:
September 30, 2010
Title:
Current views on the function of the lymphatic vasculature in health and disease
Authors:
Wang, Yingdi; Oliver, Guillermo
Abstract:
The lymphatic vascular system is essential for lipid absorption, fluid homeostasis, and immune surveillance. Until recently, lymphatic vessel dysfunction had been associated with symptomatic pathologic conditions such as lymphedema. Work in the last few years had led to a better understanding of the functional roles of this vascular system in health and disease. Furthermore, recent work has also unraveled additional functional roles of the lymphatic vasculature in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension. In this review, we summarize the functional roles of the lymphatic vasculature in health and disease.
Published:
September 30, 2010
Title:
Diagnosing diabetes in disadvantaged populations: The role of social participation
Authors:
Baig, Arshiya; Escarce, José
Abstract:
Objective:Extensive social networks improve health and reduce mortality. Our aim was to investigate the effect of social participation on the probability that people with diabetes are diagnosed by health care providers and whether these effects differ in disadvantaged populations.Methods:Using the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we included 1642 adults with diabetes. Diagnosed people with diabetes reported a provider diagnosis of diabetes; undiagnosed people with diabetes had a fasting plasma glucose over 125 mg/dl. Multivariate logistic regression models were used to assess the effect of social participation on diabetes diagnosis.Results:Increased social participation led to a higher probability of being diagnosed among people with diabetes who were low-income (OR 5 1.19, P < 0.10) and who did not graduate from high school (OR 5 1.21, P
Published:
September 30, 2010
Title:
Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity
Authors:
Yang, Xinxin; Cheng, Baohua
Abstract:
Ketogenic diet (KD) is a high-fat, low-protein and low-carbohydrate diet. It is reported that KD can provide the neuroprotection for the neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD) and amyotrophic lateral sclerosis. The main clinical symptom of PD is motor dysfunction derived from the loss of dopaminergic neurons in the substantia nigra (SN) and dopamine content in the striatum subsequently. It is well known that treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice produce motor dysfunction, biochemical, and neurochemical changes remarkably similar to idiopathic PD patients. In this study, we investigated the neuroprotective and anti-inflammatory effects of KD in MPTP-treated mice. The data showed that pretreatment with KD alleviated the motor dysfunction induced by MPTP. The decrease of Nissl-staining and tyrosine hydroxylase (TH)-positive neurons induced by MPTP was inhibited in the SN. The change of dopamine was very similar to dopaminergic neurons in the SN. KD inhibited the activation of microglia induced by MPTP in the SN. The levels of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the SN were also decreased and induced by MPTP. So, we concluded that KD was neuroprotective and anti-inflammatory against MPTP-neurotoxicity.
Published:
September 30, 2010
Title:
Expression of adipose microRNAs is sensitive to dietary conjugated linoleic acid treatment in mice
Authors:
Parra, Pilar; Serra, Francisca; Palou, Andreu
Abstract:
BACKGROUND: Investigation of microRNAs (miRNAs) in obesity, their genetic targets and influence by dietary modulators is of great interest because it may potentially identify novel pathways involved in this complex metabolic disorder and influence future therapeutic approaches. This study aimed to determine whether miRNAs expression may be influenced by conjugated linoleic acid (CLA), currently used to induce fat loss. METHODOLOGY/PRINCIPAL FINDINGS: We determined retroperitoneal adipose tissue (rWAT) expression of five miRNAs related to adipocyte differentiation (miRNA-143) and lipid metabolism (miRNA-103 and -107) and altered in obesity (miRNA-221 and -222), using the TaqMan®MicroRNA Assay (Applied-Biosystems). In the first experiment, mice were fed with a standard fat diet and orally treated with sunflower oil (control group) and 3 or 10 mg CLA/day for 37 days. In the second experiment, mice were fed with a high fat diet for 65 days. For the first 30 days, mice received the same doses of CLA described above and, from that time onwards, animals received a double dose. Results showed that expression of selected miRNAs was modified in response to CLA treatment and metabolic status. Interestingly, a strong correlation was observed between miR-103 and -107 expression, as well as miR-221 and -222 in both experiments. Moreover, changes in miRNAs expression correlated with several adipocyte gene expressions: miR-103 and -107 correlated with genes involved in fatty acid metabolism whereas miR-221 and miR-222 correlated with the expression of adipocytokines. Regarding the minor changes observed in miR-143 expression, no differences in expression of adipogenic markers were observed. CONCLUSIONS/SIGNIFICANCE: Although elucidating the functional implications of miRNAs is beyond the scope of this study, these findings provide the first evidence that miRNAs expression may be influenced by dietary manipulation, reflecting or even contributing to the new metabolic state originated by CLA treatment.
Published:
September 26, 2010
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