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Title:
Cultural and Family Challenges to Managing Type 2 Diabetes in Immigrant Chinese Americans
Authors:
Chesla, Catherine A.; Chun, Kevin M.; Kwan, Christine M. L.
Abstract:
OBJECTIVE Although Asians demonstrate elevated levels of type 2 diabetes, little attention has been directed to their unique cultural beliefs and practices regarding diabetes. We describe cultural and family challenges to illness management in foreign-born Chinese American patients with type 2 diabetes and their spouses. RESEARCH DESIGN AND METHODS This was an interpretive comparative interview study with 20 foreign-born Chinese American couples (n = 40) living with type 2 diabetes. Multiple (six to seven) semistructured interviews with each couple in individual, group, and couple settings elicited beliefs about diabetes and narratives of care within the family and community. Interpretive narrative and thematic analysis were completed. A separate respondent group of 19 patients and spouses who met the inclusion criteria reviewed and confirmed the themes developed from the initial couples. RESULTS Cultural and family challenges to diabetes management within foreign-born Chinese American families included how 1) diabetes symptoms challenged family harmony, 2) dietary prescriptions challenged food beliefs and practices, and 3) disease management requirements challenged established family role responsibilities. CONCLUSIONS Culturally nuanced care with immigrant Chinese Americans requires attentiveness to the social context of disease management. Patients' and families' disease management decisions are seldom made independent of their concerns for family well-being, family face, and the reciprocal responsibilities required by varied family roles. Framing disease recommendations to include cultural concerns for balance and significant food rituals are warranted.
Published:
September 30, 2009
Title:
Effects of plant-based diets on plasma lipids
Authors:
Ferdowsian, Hope R.; Barnard, Neal D.
Abstract:
Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.
Published:
September 30, 2009
Title:
Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice
Authors:
Pocai, A.; Carrington, P. E.; Adams, J. R.; Wright, M.; Eiermann, G.; Zhu, L.; Du, X.; Petrov, A.; Lassman, M. E.; Jiang, G.; Liu, F.; Miller, C.; Tota, L. M.; Zhou, G.; Zhang, X.; Sountis, M. M.; Santoprete, A.; Capito', E.; Chicchi, G. G.; Thornberry, N.; Bianchi, E.; Pessi, A.; Marsh, D. J.; SinhaRoy, R.
Abstract:
Published:
September 30, 2009
Title:
Isotopic evidence for the diets of European Neanderthals and early modern humans
Authors:
Richards, Michael P.; Trinkaus, Erik
Abstract:
We report here on the direct isotopic evidence for Neanderthal and early modern human diets in Europe. Isotopic methods indicate the sources of dietary protein over many years of life, and show that Neanderthals had a similar diet through time (≈120,000 to ≈37,000 cal BP) and in different regions of Europe. The isotopic evidence indicates that in all cases Neanderthals were top-level carnivores and obtained all, or most, of their dietary protein from large herbivores. In contrast, early modern humans (≈40,000 to ≈27,000 cal BP) exhibited a wider range of isotopic values, and a number of individuals had evidence for the consumption of aquatic (marine and freshwater) resources. This pattern includes Oase 1, the oldest directly dated modern human in Europe (≈40,000 cal BP) with the highest nitrogen isotope value of all of the humans studied, likely because of freshwater fish consumption. As Oase 1 was close in time to the last Neanderthals, these data may indicate a significant dietary shift associated with the changing population dynamics of modern human emergence in Europe.
Published:
September 21, 2009
Title:
Carbohydrate Restriction, as a First-Line Dietary Intervention, Effectively Reduces Biomarkers of Metabolic Syndrome in Emirati Adults
Authors:
Al-Sarraj, Taif; Saadi, Hussein; Calle, Mariana C.; Volek, Jeff S.; Fernandez, Maria Luz
Abstract:
Abstract. The prevalence of diabetes mellitus (DM) in the United Arab Emirates is among the highest world-wide. Metabolic syndrome (MetS) predisposes individua
Published:
August 31, 2009
Title:
Effects of a Diet Higher in Carbohydrate/Lower in Fat Versus Lower in Carbohydrate/Higher in Monounsaturated Fat on Postmeal Triglyceride Concentrations and Other Cardiovascular Risk Factors in Type 1 Diabetes
Authors:
Strychar, Irene; Cohn, Jeffrey S.; Renier, Geneviève; Rivard, Michèle; Aris-Jilwan, Nahla; Beauregard, Hugues; Meltzer, Sara; Bélanger, André; Dumas, Richard; Ishac, Alain; Radwan, Farouk; Yale, Jean-François
Abstract:
OBJECTIVE To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride (TG) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control. RESEARCH DESIGN AND METHODS In a parallel group design study, 30 subjects were randomly assigned and completed one of the two eucaloric diets. Assessments included: BMI, blood pressure, A1C, plasma lipids, and markers of oxidation, thrombosis, and inflammation. At 6 months, subjects were hospitalized for 24 h to measure plasma TG excursions. RESULTS There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 (PAI-1) levels and weight gain in the lower-carbohydrate/higher–monounsaturated fat group. During the 24-h testing, the lower-carbohydrate/higher–monounsaturated fat group had a lower plasma TG profile. CONCLUSIONS A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control.
Published:
August 31, 2009
Title:
Revisiting the dietary niche: When is a mammalian herbivore a specialist?
Authors:
Shipley, Lisa; Forbey, Jennifer; Moore, Benjamin
Abstract:
Understanding dietary specialization in herbivores has theoretical and practical implications in ecology, yet defining niche breadth consistently has been problematic. To increase clarity and communication among ecologists and among disciplines (i.e., chemists, pharmacologists), we propose a specialization key for mammalian herbivores that assigns "obligatory" and "facultative" modifiers to the terms "specialist" and "generalist". These modifiers are assigned based on (1) relative breadth of the animal's realized niche and diet (what it eats), (2) relative breadth of the fundamental niche and available diet (what it could eat), (3) the extent of chemical or physical characteristics, termed "difficulty", that make food items either low in value or unpalatable to most herbivores, and (4) relevant temporal and spatial scales at which diets and niche breadth were measured. Obligatory specialists always have a narrow realized niche consisting of difficult food items, and morphological adaptations and/or the loss of redundant behavioral flexibility that effectively limit their fundamental niches, precluding them from expanding their diet under changed environmental conditions. Facultative specialists have a consistently narrow realized niche for difficult foods during at least one spatial or temporal scale, but have a broad enough fundamental niche to allow them to expand their diet to include less difficult foods when environmental conditions allow. Facultative generalists have the broadest fundamental niche, allowing them to consume a wide variety of foods. However, they may occasionally demonstrate a narrow realized niche, focused on less difficult plants than is the case with specialists. Finally, the obligatory generalists always have a wide realized niche because of a relatively narrow fundamental niche, precluding them from eating much of any difficult plant. We summarize hypothesized characteristics of mammalian herbivores in each of the four categories of specialization. We demonstrate the need for further work on defining the realized and fundamental niches, comparing among herbivores across categories conducted under similar conditions, and understanding the nature of trade-offs required for specialization and generalization for both community and phylogenetically based analyses.
Published:
August 31, 2009
Title:
Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development
Authors:
Waterland, Robert A.; Kellermayer, Richard; Rached, Marie-Therese; Tatevian, Nina; Gomes, Marcus V.; Zhang, Jiexin; Zhang, Li; Chakravarty, Abrita; Zhu, Wei; Laritsky, Eleonora; Zhang, Wenjuan; Wang, Xiaodan; Shen, Lanlan
Abstract:
The question of whether DNA methylation contributes to the stabilization of gene expression patterns in differentiated mammalian tissues remains controversial. Using genome-wide methylation profiling, we screened 3757 gene promoters for changes in methylation during postnatal liver development to test the hypothesis that developmental changes in methylation and expression are temporally correlated. We identified 31 genes that gained methylation and 111 that lost methylation from embryonic day 17.5 to postnatal day 21. Promoters undergoing methylation changes in postnatal liver tended not to be associated with CpG islands. At most genes studied, developmental changes in promoter methylation were associated with expression changes, suggesting both that transcriptional inactivity attracts de novo methylation, and that transcriptional activity can override DNA methylation and successively induce developmental hypomethylation. These in vivo data clearly indicate a role for DNA methylation in mammalian differentiation, and provide the novel insight that critical windows in mammalian developmental epigenetics extend well beyond early embryonic development.
Published:
August 14, 2009
Title:
Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial
Authors:
Henderson, Samuel T.; Vogel, Janet L.; Barr, Linda J.; Garvin, Fiona; Jones, Julie J.; Costantini, Lauren C.
Abstract:
BACKGROUND: Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. METHODS: Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at http://clinicaltrials.gov/ct2/show/NCT00142805 RESULTS: AC-1202 significantly elevated a serum ketone body (beta-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change from Baseline in ADAS-Cog scores at Day 45 (p = 0.0005) and a 3.36 point difference at Day 90 (p = 0.0148) compared to Placebo. In the per protocol population, E4(-) participants receiving AC-1202 (N = 37) differed from placebo by 5.73 points at Day 45 (p = 0.0027) and by 4.39 points at Day 90 (p = 0.0143). In the dosage compliant population, E4(-) participants receiving AC-1202 differed from placebo by 6.26 points at Day 45 (p = 0.0011, N = 38) and 5.33 points at Day 90 (p = 0.0063, N = 35). Furthermore, a significant pharmacologic response was observed between serum beta-hydroxybutyrate levels and change in ADAS-Cog scores in E4(-) subjects at Day 90 (p = 0.008). Adverse events occurred more frequently in AC-1202 subjects, were primarily restricted to the gastrointestinal system, and were mainly mild to moderate in severity and transient in nature. CONCLUSION: AC-1202 rapidly elevated serum ketone bodies in AD patients and resulted in significant differences in ADAS-Cog scores compared to the Placebo. Effects were most notable in APOE4(-) subjects who were dosage compliant.
Published:
August 9, 2009
Title:
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
Authors:
Cani, P. D.; Possemiers, S.; Van de Wiele, T.; Guiot, Y.; Everard, A.; Rottier, O.; Geurts, L.; Naslain, D.; Neyrinck, A.; Lambert, D. M.; Muccioli, G. G.; Delzenne, N. M.
Abstract:
Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagonderived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.
Published:
July 31, 2009
Title:
Quality of Diabetes Care for Immigrants in the U.S.
Authors:
Dallo, Florence J.; Wilson, Fernando A.; Stimpson, Jim P.
Abstract:
OBJECTIVE To compare achievement of the American Diabetes Association diabetes care recommendations for U.S.- and foreign-born individuals with diabetes. RESEARCH DESIGN AND METHODS Using the 2001–2006 Medical Expenditure Panel Surveys, we report estimates for receipt of a cholesterol test, routine checkup, influenza vaccination, eye examination, dental checkup, foot examination, and two or more A1C tests in 1 year for foreign- (n = 1,272) and U.S.-born (n = 5,811) individuals aged ≥18 years. We define a dichotomous variable representing full compliance with the above examinations. We provide descriptive characteristics of the sample and use multivariable analysis for each procedure with random effects logit regression. RESULTS Compared with U.S.-born individuals with diabetes, foreign-born individuals are younger, have lower education levels and income, are more likely to have public or no insurance, and are less likely to have a usual source of care. With adjustment for all potential confounders, foreign-born individuals are less likely to report having had an influenza vaccination (odds ratio 0.51 [95% CI 0.31–0.71]) or to be compliant with any one of the seven recommendations (0.64 [0.34–0.95]). CONCLUSIONS These findings demonstrate that immigrants are less likely than U.S.-born individuals with diabetes to adhere to any one of seven diabetes care recommendations in general and, specifically, are less likely to report having received an influenza vaccination. Because immigrants are less likely to use health care, clinicians should take advantage of the office visit to effectively communicate to the patient the importance of receiving an influenza vaccination.
Published:
July 31, 2009
Title:
A randomized controlled trial on the efficacy of carbohydrate-reduced or fat-reduced diets in patients attending a telemedically guided weight loss program
Authors:
Frisch, Sabine; Zittermann, Armin; Berthold, Heiner K.; Götting, Christian; Kuhn, Joachim; Kleesiek, Knut; Stehle, Peter; Körtke, Heinrich
Abstract:
We investigated whether macronutrient composition of energy-restricted diets influences the efficacy of a telemedically guided weight loss program.
Published:
July 17, 2009
Title:
Mentoring in Psychiatric Residency Programs: A Survey of Chief Residents
Authors:
Lis, L. D.; Wood, W. C.; Petkova, E.; Shatkin, J.
Abstract:
Objective: Mentorship is an important component of graduate education. This study assessed the perceptions of general psychiatry chief residents regarding the adequacy of mentorship provided during training. Methods: The authors surveyed 229 chief residents participating in the APA National Chief Residents Leadership Program in 2004 and 2005. The survey assessed domains such as work hours, didactics, home and family life, and mentorship. Results: Of the chief psychiatric residents surveyed, 49% reported that they did not have a clearly defined career development mentor, and 39% reported that they did not feel adequately mentored. Gender, race/ethnicity, marital status, moonlighting, medical school (American versus international), and type of residency program (academic versus community based) did not show significant association with either “having a clearly defined mentor” or “feeling adequately mentored,” based on chisquared tests for independence. Chief residents who had authored peer-reviewed publications were significantly more likely to report having a clearly defined mentor and to feel adequately mentored than those who did not author publications. Logistic regression analysis showed that having a clearly defined mentor was associated with twice the odds for feeling well prepared to practice psychiatry upon graduation compared with those who did not have a clearly defined mentor, even after controlling for gender, race, medical school, and residency program type. Conclusion: Half of the psychiatric chief residents surveyed reported the lack of a clearly defined career development mentor. In addition, a chief resident’s response of lacking a clear mentor was associated with the perception of being less prepared to
Published:
June 30, 2009
Title:
Neandertals paleoenvironment in Western Provence: The contribution of Les Auzières 2 (Méthamis, Vaucluse, France)
Authors:
Marchal, François; Monchot, Hervé; Coussot, Céline; Desclaux, Emmanuel; Deschamps, Pierre; Thiébaut, Céline; Bahain, Jean-Jacques; Falguères, Christophe; Dolo, Jean-Michel
Abstract:
The site of Les Auzières 2 (Méthamis, Vaucluse) was excavated from 2001 to 2005. It yielded an original and diverse fauna, unique in southeastern France (Provence). The spectrum of large mammals comprises 14 species including hyena, horse, ibex, woolly rhinoceros, giant deer and mammoth. Lithic artifacts are rare but testify to the presence of a Mousterian industry. All of these remains derive from layers that have been dated to 60 ± 10 ka by ESR/U-series method. Les Auzières 2 is of special importance for examining the issue of human/carnivore interaction in the Pleistocene since it has yielded a large assemblage of carnivore remains, and probably represents a hyena den. The diverse fauna offers a more comprehensive picture of Upper Pleistocene biodiversity in southeastern France than that usually provided by sites with a stronger anthropogenic signal.
Published:
June 30, 2009
Title:
Sex differences in energy homeostatis following a diet relatively high in protein exchanged with carbohydrate, assessed in a respiration chamber in humans
Authors:
Westerterp-Plantenga, Margriet S.; Lejeune, Manuela P. G. M.; Smeets, Astrid J. P. G.; Luscombe-Marsh, Natalie D.
Abstract:
CONTEXT: Obesity prevalence is generally higher in women than in men, and a paucity of research with sex-specific approaches exists. The question arises whether current weight loss programmes, largely developed and tested on women, are appropriate for men. OBJECTIVE: Investigate 24 h energy metabolism, satiety and related hormones during a diet relatively high in protein (HP), exchanged with carbohydrate compared to an adequate-protein (AP) diet, in a respiration chamber in men, in comparison with previous outcomes in women. DESIGN: Ten healthy males (BMI: 22.5+/-1.6 kg/m(2), age: 25+/-3.5 y) were fed in energy balance with an AP (10/60/30% of energy of protein/carbohydrate/fat) or a HP (30/40/30% of energy of protein/carbohydrate/fat) diet in a randomized cross-over design. RESULTS: During the HP diet, 24 h Energy Expenditure (10.5+/-0.5 vs 10.0+/-0.5 MJ/d; p<0.05), Sleeping Energy Expenditure (7.1+/-0.3 vs 6.9+/-0.2 MJ/d; p<0.05), protein balance (0.5+/-0.02 vs 0.0+/-0.01 MJ/d; p<0.05), satiety (AUC) p<0.05, and plasma GLP-1 concentrations (42+/-23 vs 28+/-16 AUC; p<0.005) were significantly higher and 24 h RQ (0.80 vs 0.85; p<0.01), fat balance (-0.85+/-0.03 vs 0.05 vs 0.03 MJ/d; p<0.01) and hunger (AUC) p
Published:
June 21, 2009
Title:
The effect of a plant-based low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects
Authors:
Jenkins, David J. A.; Wong, Julia M. W.; Kendall, Cyril W. C.; Esfahani, Amin; Ng, Vivian W. Y.; Leong, Tracy C. K.; Faulkner, Dorothea A.; Vidgen, Ed; Greaves, Kathryn A.; Paul, Gregory; Singer, William
Abstract:
BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.
Published:
June 7, 2009
Title:
A Very Low-Carbohydrate Diet Improves Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel Syndrome
Authors:
Austin, Gregory L.; Dalton, Christine B.; Hu, Yuming; Morris, Carolyn B.; Hankins, Jane; Weinland, Stephan R.; Westman, Eric C.; Yancy, William S.; Drossman, Douglas A.
Abstract:
Background & Aims Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D. Methods Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured. Results Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 ± 0.8/d to 1.4 ± 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 ± 0.7 to 3.8 ± 1.2; P
Published:
May 31, 2009
Title:
Dietary Carbohydrates and Dental-Systemic Diseases
Authors:
Hujoel, P.
Abstract:
Two contradictory hypotheses on the role of dietary carbohydrates in health and disease shape how dental-systemic associations are regarded. On one side, Cleave and Yudkin postulated that excessive dietary fermentable carbohydrate intake led—in the absence of dental interventions such as fluorides—first to dental diseases and then to systemic diseases. Under this hypothesis, dental and systemic diseases shared—as a common cause—a diet of excess fermentable carbohydrates. Dental diseases were regarded as an alarm bell for future systemic diseases, and restricting carbohydrate intake prevented both dental and systemic diseases. On the opposite side, Keys postulated the lipid hypothesis: that excessive dietary lipid intake caused systemic diseases. Keys advocated a diet high in fermentable carbohydrate for the benefit of general health, and dental diseases became regarded as local dietary side effects. Because general health takes precedence over dental health when it comes to dietary recommendations, dental diseases became viewed as local infections; interventions such as fluorides, sealants, oral hygiene, antimicrobials, and dental fillings became synonymous with maintaining dental health, and carbohydrates were no longer considered as a common cause for dental-systemic diseases. These opposing dietary hypotheses have increasingly been put to the test in clinical trials. The emerging trial results favor Cleave-Yudkin’s hypothesis and may affect preventive approaches for dental and systemic diseases.
Published:
May 31, 2009
Title:
Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2
Authors:
Fine, Eugene J.; Miller, Anna; Quadros, Edward V.; Sequeira, Jeffrey M.; Feinman, Richard D.
Abstract:
BACKGROUND: Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA) enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. METHODS: Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM), or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. RESULTS: There was a high correlation of cell growth with ATP concentration (r = 0.948) in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p
Published:
May 28, 2009
Title:
Herodotus on Diet and Longevity: How the Persians Fed on Dung and Lived to 80, While the Tall, Handsome Ethiopians Ate Boiled Meat and Lived Beyond 120
Authors:
Finch, Caleb E.
Abstract:
Herodotus' Histories tell of diet and longevity: the Persians, who ate bread from grain fertilized with dung lived but 80 years, while the tall handsome Ethiopeans ate boiled meat and lived more than 120. These and other ancient texts anticipate current biomedical understanding of aging. However, there little evidence for supracentenarians in the ancient world as noted in Herodotus, Genesis, and other classical texts: only recently have centenarians emerged as a significant age group. Nutrition and hygiene have been major factors in the increasing longevity and of adult height since 1800. It remains possible that some ancient elites achieved modern longevity.
Published:
May 28, 2009
Title:
Understanding the Warburg effect: the metabolic requirements of cell proliferation
Authors:
Vander Heiden, Matthew G.; Cantley, Lewis C.; Thompson, Craig B.
Abstract:
In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
Published:
May 21, 2009
Title:
Effects of a popular exercise and weight loss program on weight loss, body composition, energy expenditure and health in obese women
Authors:
Kerksick, Chad; Thomas, Ashli; Campbell, Bill; Taylor, Lem; Wilborn, Colin; Marcello, Brandon; Roberts, Mike; Pfau, Emily; Grimstvedt, Megan; Opusunju, Jasmine; Magrans-Courtney, Teresa; Rasmussen, Christopher; Wilson, Ron; Kreider, Richard B.
Abstract:
OBJECTIVE: To determine the safety and efficacy of altering the ratio of carbohydrate and protein in low-energy diets in conjunction with a popular exercise program in obese women. DESIGN: Matched, prospective clinical intervention study to assess efficacy of varying ratios of carbohydrate and protein intake in conjunction with a regular exercise program. PARTICIPANTS: One-hundred sixty one sedentary, obese, pre-menopausal women (38.5 ± 8.5 yrs, 164.2 ± 6.7 cm, 94.2 ± 18.8 kg, 34.9 ± 6.4 kg.m⁻², 43.8 ± 4.2%) participated in this study. Participants were weight stable and not participating in additional weight loss programs. METHODS: Participants were assigned to either a no exercise + no diet control (CON), a no diet + exercise group (ND), or one of four diet + exercise groups (presented as kcals; % carbohydrate: protein: fat): 1) a high energy, high carbohydrate, low protein diet (HED) [2,600; 55:15:30%], 2) a very low carbohydrate, high protein diet (VLCHP) [1,200 kcals; 63:7:30%], 3) a low carbohydrate, moderate protein diet (LCMP) [1,200 kcals; 50:20:30%] and 4) a high carbohydrate, low protein diet (HCLP) [1,200 kcals; 55:15:30%]. Participants in exercise groups (all but CON) performed a pneumatic resistance-based, circuit training program under supervision three times per week. MEASUREMENTS: Anthropometric, body composition, resting energy expenditure (REE), fasting blood samples and muscular fitness assessments were examined at baseline and weeks 2, 10 and 14. RESULTS: All groups except CON experienced significant reductions (P < 0.05 - 0.001) in waist circumference over 14 weeks. VLCHP, LCHP and LPHC participants experienced similar but significant (P < 0.05 - 0.001) reductions in body mass when compared to other groups. Delta responses indicated that fat loss after 14 weeks was significantly greatest in VLCHP (95% CI: -5.2, -3.2 kg), LCMP (-4.0, -1.9 kg) and HCLP (-3.8, -2.1 kg) when compared to other groups. Subsequent reductions in % body fat were significantly greater in VLCHP, LCMP and HCLP participants. Initial dieting decreased (P < 0.05) relative REE similarly in all groups. All exercise groups significantly (P < 0.05) improved in muscular fitness, but these improvements were not different among groups. Favorable but non-significant mean changes occurred in lipid panels, glucose and HOMA-IR. Leptin levels decreased (P
Published:
May 13, 2009
Title:
Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes
Authors:
Haimoto, Hajime; Sasakabe, Tae; Wakai, Kenji; Umegaki, Hiroyuki
Abstract:
We previously demonstrated that a loosely restricted 45%-carbohydrate diet led to greater reduction in hemoglobin A1c (HbA1c) compared to high-carbohydrate diets in outpatients with mild type 2 diabetes (mean HbA1c level: 7.4%) over 2 years. To determine whether good glycemic control can be achieved with a 30%-carbohydrate diet in severe type 2 diabetes, 33 outpatients (15 males, 18 females, mean age: 59 yrs) with HbA1c levels of 9.0% or above were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs. HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months. Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6 months (23.5 ± 3.4). Only two patients dropped out. No adverse effects were observed except for mild constipation. The number of patients on sulfonylureas decreased from 7 at baseline to 2 at 6 months. No patient required inpatient care or insulin therapy. In summary, the 30%-carbohydrate diet over 6 months led to a remarkable reduction in HbA1c levels, even among outpatients with severe type 2 diabetes, without any insulin therapy, hospital care or increase in sulfonylureas. The effectiveness of the diet may be comparable to that of insulin therapy.
Published:
May 5, 2009
Title:
Constructing genomic maps of positive selection in humans: Where do we go from here?
Authors:
Akey, Joshua M.
Abstract:
Identifying targets of positive selection in humans has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to systematically interrogate the entire genome for signatures of natural selection. To date, 21 genome-wide scans for recent or ongoing positive selection have been performed in humans. A key challenge is to begin synthesizing these newly constructed maps of positive selection into a coherent narrative of human evolutionary history and derive a deeper mechanistic understanding of how natural populations evolve. Here, I chronicle the recent history of the burgeoning field of human population genomics, critically assess genome-wide scans for positive selection in humans, identify important gaps in knowledge, and discuss both short- and long-term strategies for traversing the path from the low-resolution, incomplete, and error-prone maps of selection today to the ultimate goal of a detailed molecular, mechanistic, phenotypic, and population genetics characterization of adaptive alleles.
Published:
April 30, 2009
Title:
Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans
Authors:
Stanhope, Kimber L.; Schwarz, Jean Marc; Keim, Nancy L.; Griffen, Steven C.; Bremer, Andrew A.; Graham, James L.; Hatcher, Bonnie; Cox, Chad L.; Dyachenko, Artem; Zhang, Wei; McGahan, John P.; Seibert, Anthony; Krauss, Ronald M.; Chiu, Sally; Schaefer, Ernst J.; Ai, Masumi; Otokozawa, Seiko; Nakajima, Katsuyuki; Nakano, Takamitsu; Beysen, Carine; Hellerstein, Marc K.; Berglund, Lars; Havel, Peter J.
Abstract:
Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.
Published:
April 30, 2009
Title:
Meta-analysis of animal fat or animal protein intake and colorectal cancer
Authors:
Alexander, Dominik D.; Cushing, Colleen A.; Lowe, Kimberly A.; Sceurman, Bonnie; Roberts, Mark A.
Abstract:
ABSTRACT. Background: In the recent World Cancer Research Fund/American Institute for Cancer Research report of diet and cancer, it was concluded that there is
Published:
April 30, 2009
Title:
The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo
Authors:
Schwinkendorf, D.; Gallant, P.
Abstract:
Myc proto-oncoproteins are important regulators of growth and proliferation in development. Their functions have been evolutionarily conserved from insects to vertebrates, although the sequence conservation is limited to a few short domains. Here, we analyze the requirement for the most highly conserved domains, called Myc boxes 2 and 3 (MB2 and MB3), and for the weakly conserved N-terminus for the biological activity of the single Drosophila Myc protein in the animal in vivo. We find that a Myc mutant lacking the N-terminus retains very little activity, whereas Myc transgenes carrying a deletion of MB3 have a moderately increased ability to promote growth and apoptosis; mutation of MB2 reduces transcriptional output and the biological activities of Myc. Surprisingly though, Myc without MB2 retains enough activity to partially rescue the lethality of a Myc null mutation. Thus, although MB2 and MB3 are highly conserved in evolution, loss of either domain has comparatively mild consequences on Myc activity in vivo.
Published:
April 30, 2009
Title:
Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS)
Authors:
Poluzzi, Elisabetta; Raschi, Emanuel; Moretti, Ugo; De Ponti, Fabrizio
Abstract:
Methods Reports of TdP from January 2004 through December 2007 were retrieved from the public version of the AERS database. All reports were selected from REACTION files and the relevant suspected and/or interacting drugs were identified from DRUG files. Qualitative analysis was performed by the case/non-case method. Cases were represented by TdP reports, whereas non-cases were all reports of adverse drug reactions other than TdP. Quantitative analysis was assessed by calculating the crude and adjusted reporting odds ratio (ROR), as a measure of disproportionality, with the 95% confidence interval. Results Reports of TdP were 1665 over a 4-year period, involving 376 active substances. Thirty-five drugs with at least 10 reports were identified: amiodarone and methadone were associated with the highest number of cases (113 and 83 respectively) and most of the other reports were ascribable to antibacterials, antidepressants and antipsychotics; remarkable differences in number of cases and ROR were present among agents within each therapeutic class. A disproportionate reporting was also observed for other compounds such as donepezil, famotidine and mitoxantrone. Conclusions Large spontaneous reporting databases represent an important source for signal detection of rare adverse drug reactions (ADR), such as TdP. The number of reports associated to donepezil, famotidine and mitoxantrone could be considered unexpected on the basis of current evidence and needs further investigations on their true TdP-liability. Copyright # 2009 John Wiley & Sons, Ltd.
Published:
April 7, 2009
Title:
Prediction of breast cancer by profiling of urinary RNA metabolites using Support Vector Machine-based feature selection
Authors:
Henneges, Carsten; Bullinger, Dino; Fux, Richard; Friese, Natascha; Seeger, Harald; Neubauer, Hans; Laufer, Stefan; Gleiter, Christoph H.; Schwab, Matthias; Zell, Andreas; Kammerer, Bernd
Abstract:
BACKGROUND: Breast cancer belongs to the most frequent and severe cancer types in human. Since excretion of modified nucleosides from increased RNA metabolism has been proposed as a potential target in pathogenesis of breast cancer, the aim of the present study was to elucidate the predictability of breast cancer by means of urinary excreted nucleosides. METHODS: We analyzed urine samples from 85 breast cancer women and respective healthy controls to assess the metabolic profiles of nucleosides by a comprehensive bioinformatic approach. All included nucleosides/ribosylated metabolites were isolated by cis-diol specific affinity chromatography and measured with liquid chromatography ion trap mass spectrometry (LC-ITMS). A valid set of urinary metabolites was selected by exclusion of all candidates with poor linearity and/or reproducibility in the analytical setting. The bioinformatic tool of Oscillating Search Algorithm for Feature Selection (OSAF) was applied to iteratively improve features for training of Support Vector Machines (SVM) to better predict breast cancer. RESULTS: After identification of 51 nucleosides/ribosylated metabolites in the urine of breast cancer women and/or controls by LC- ITMS coupling, a valid set of 35 candidates was selected for subsequent computational analyses. OSAF resulted in 44 pairwise ratios of metabolite features by iterative optimization. Based on this approach ultimately estimates for sensitivity and specificity of 83.5% and 90.6% were obtained for best prediction of breast cancer. The classification performance was dominated by metabolite pairs with SAH which highlights its importance for RNA methylation in cancer pathogenesis. CONCLUSION: Extensive RNA-pathway analysis based on mass spectrometric analysis of metabolites and subsequent bioinformatic feature selection allowed for the identification of significant metabolic features related to breast cancer pathogenesis. The combination of mass spectrometric analysis and subsequent SVM-based feature selection represents a promising tool for the development of a non-invasive prediction system.
Published:
April 4, 2009
Title:
RAGE: a novel biological and genetic marker for vascular disease
Authors:
Kalea, Anastasia Z.; Schmidt, Ann Marie; Hudson, Barry I.
Abstract:
RAGE [receptor for AGEs (advanced glycation end-products)] plays an important role in the development and progression of vascular disease. Studies in cultured cells and small animal models of disease have clearly demonstrated that RAGE is central to the pathogenesis of vascular disease of the macro- and micro-vessels in both the diabetic and non-diabetic state. Emerging results from human clinical studies have revealed that levels of circulating soluble RAGE in the plasma may reflect the presence and/or extent of vascular disease state. Additionally, genetic variants of the RAGE gene (AGER in HUGO nomenclature) have been associated with vascular disease risk. Combining RAGE circulating protein levels and the presence of particular RAGE polymorphisms may be a useful clinical tool for the prediction of individuals at risk for vascular disease. Therapeutic intervention targeted at the RAGE gene may therefore be a useful means of treating pathologies of the vasculature.
Published:
March 31, 2009
Title:
Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis
Authors:
Yan, Lin; Spitznagel, Edward L.
Abstract:
Background: Epidemiologic studies have shown that the consumption of soy foods may be associated with a reduction in cancer risk in humans.Objective: The purpose of this study was to conduct a meta-analysis on the association between soy consumption and prostate cancer risk in men.Design: We systematically reviewed studies obtained through a thorough Medline literature search and identified 15 epidemiologic publications on soy consumption and 9 on isoflavones in association with prostate cancer risk. We extracted the most adjusted relative risks (RRs) and odds ratios (ORs) of the highest and the lowest reported categories of intake from each study and conducted this analysis using a random-effects model in which studies with smaller SEEs are given greater weight in the summary measure.Results: Our analysis of studies on soy intake yielded a combined RR/OR of 0.74 (95% CI: 0.63, 0.89; P = 0.01). When separately analyzed, studies on nonfermented soy foods yielded a combined RR/OR of 0.70 (95% CI: 0.56, 0.88; P = 0.01) and those on fermented soy foods yielded a combined RR/OR of 1.02 (95% CI: 0.73, 1.42; P = 0.92). The analysis of studies on isoflavones yielded a combined RR/OR of 0.88 (95% CI: 0.76, 1.02; P = 0.09). Further separate analyses showed a combined RR/OR of 0.52 (95% CI: 0.34, 0.81; P = 0.01) from studies with Asian populations and 0.99 (95% CI: 0.85, 1.16; P = 0.91) from studies with Western populations.Conclusions: The results of this analysis suggest that consumption of soy foods is associated with a reduction in prostate cancer risk in men. This protection may be associated with the type and quantity of soy foods consumed.
Published:
March 31, 2009
Title:
Genetic interaction analysis for DRD4 and DAT1 genes in a group of Mexican ADHD patients
Authors:
Gabriela, Martínez-Levy; John, Díaz-Galvis; Magdalena, Briones-Velasco; Ariadna, Gómez-Sánchez; Francisco, De la Peña-Olvera; Liz, Sosa-Mora; Lino, Palacios-Cruz; Josefina, Ricardo-Garcell; Ernesto, Reyes-Zamorano; Carlos, Cruz-Fuentes
Abstract:
Attention-deficit hyperactivity disorder (ADHD) is a clinically complex and multifactorial psychiatric disorder of inattention, hyperactivity and impulsivity. Family, twin and adoption studies suggest a genetic influence in the etiology of ADHD. Two variable number of tandem repeats (VNTR) polymorphic systems have been frequently associated with this disorder: the 7 repeat (R) allele in exon 3 of the dopamine receptor D4 (DRD4) and the 10R allele located in the 3' untranslated region (UTR) of the dopamine transporter (DAT1). We conducted a case-control association study between ADHD and these polymorphisms in a group of adolescent inhabitants of the metropolitan area of Mexico City. In addition, we evaluated the interaction between these genes, the disorder and its associated psychiatric comorbidities. No positive association between ADHD and the 7R allele of DRD4 or the 10R allele of DAT1 was observed; however, compared to controls, patients with internalized comorbidities had a lesser frequency of genotypes with the 7R allele of DRD4 and the 10/10 genotype of DAT1. A logistic regression analysis showed that the simultaneous absence of the 10/10 DAT1 and 7/7 DRD4 genotypes predicts membership to the group of ADHD patients with internalized comorbidities (e.g. anxiety, depression). Our results highlight the importance of cross-ethnic research and the possibility of a distinct genetic basis that underlies the type of comorbidities associated with ADHD. This result should be considered in terms of the study design, and further replication is necessary in an independent sample.
Published:
February 26, 2009
Title:
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature
Authors:
Kraft, Bryan D.; Westman, Eric C.
Abstract:
We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Published:
February 25, 2009
Title:
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature
Authors:
Kraft, Bryan D.; Westman, Eric C.
Abstract:
We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Published:
February 25, 2009
Title:
Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study
Authors:
Reams, R. Renee; Agrawal, Deepak; Davis, Melissa B.; Yoder, Sean; Odedina, Folakemi T.; Kumar, Nagi; Higginbotham, Joseph M.; Akinremi, Titilola; Suther, Sandra; Soliman, Karam FA
Abstract:
African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p
Published:
February 9, 2009
Title:
CD44 expression is a feature of prostatic small cell Carcinoma and Distinguishes it from its Mimickers
Authors:
Simon, Rochelle A.; di Sant'Agnese, P. Anthony; Huang, Li-Shan; Xu, Haodong; Yao, Jorge L.; Yang, Qi; Liang, Sharon; Liu, Jinsong; Yu, Rena; Cheng, Liang; Oh, William K.; Palapattu, Ganesh S.; Wei, Jianjun; Huang, Jiaoti
Abstract:
Summary Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P
Published:
January 31, 2009
Title:
Clinical Review: Bisphosphonate Use in Childhood Osteoporosis
Authors:
Bachrach, Laura K; Ward, Leanne M
Abstract:
Context: As awareness of osteoporosis in childhood has increased, so have pressures to consider use of the pharmacological agents used to treat osteoporosis in adults. This review examines available research on the efficacy and safety of bisphosphonate therapy for pediatric osteoporosis. Evidence Acquisition: We reviewed the medical literature for key articles and consensus statements on the use of bisphosphonates in children through June 2008. Evidence Synthesis: We compared reports using varying bisphosphonate agents, doses, and duration of therapy to treat osteogenesis imperfecta and a variety of secondary causes of osteoporosis in children. Conclusions drawn from a recently published Cochrane analysis and the consensus statements from experts in the field were considered as well. Conclusions: Use of bisphosphonate therapy in pediatric patients remains controversial because of inadequate long-term efficacy and safety data. For this reason, many experts recommend limiting use of these agents to those children with recurrent extremity fractures, symptomatic vertebral collapse, and reduced bone mass. Current data are inadequate to support the use of bisphosphonates in children to treat reductions in bone mass/density alone. More research is needed to define appropriate indications for bisphosphonate therapy and the optimal agent, dose, and duration of use in pediatric patients.
Published:
January 31, 2009
Title:
Metabolic syndrome and major depressive disorder: Co-occurrence and pathophysiologic overlap
Authors:
McIntyre, Roger S.; Rasgon, Natalie L.; Kemp, David E.; Nguyen, Ha T.; Law, Candy W. Y.; Taylor, Valerie H.; Woldeyohannes, Hanna O.; Alsuwaidan, Mohammad T.; Soczynska, Joanna K.; Kim, Byungsu; Lourenco, Maria T.; Kahn, Linda S.; Goldstein, Benjamin I.
Abstract:
The metabolic syndrome and its components are associated with depressive symptomatology. This article discusses the rate of co-occurrence and the points of pathophysiologic commonality between the metabolic syndrome and major depressive disorder.
Published:
January 31, 2009
Title:
Caloric restriction improves memory in elderly humans
Authors:
Witte, A. V.; Fobker, M.; Gellner, R.; Knecht, S.; Flöel, A.
Abstract:
Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m2) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < −0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.
Published:
January 26, 2009
Title:
Circulating Lipoproteins Are a Crucial Component of Host Defense against Invasive Salmonella typhimurium Infection
Authors:
Netea, Mihai G.; Joosten, Leo A. B.; Keuter, Monique; Wagener, Frank; Stalenhoef, Anton F. H.; van der Meer, Jos W. M.; Kullberg, Bart Jan
Abstract:
Published:
January 20, 2009
Title:
Intention-to-treat. What is the question?
Authors:
Feinman, Richard D.
Abstract:
It has become commonplace for Randomized Controlled Trials (RCTs) to be analyzed according to Intention-to-Treat (ITT) principles in which data from all subjects are used regardless of the subjects' adherence to protocol. While ITT analyses can provide useful information in some cases, they do not answer the question that motivates many RCTs, namely, whether the treatments differ in efficacy. ITT tends to reduce information by combining two questions, whether the intervention is effective and whether, as implemented, it has good compliance. Because these questions may be separate there is a risk of misuse. Two examples are presented that demonstrate this potential for abuse: a study on the effectiveness of vitamin E in reducing cardiovascular risk and comparisons of low fat and low carbohydrate diets. In the first case, a treatment that is demonstrably effective is described as without merit. In the second, ITT describes as the same, two diets that actually have different outcomes. These misuses of ITT are not atypical and are not technical problems in statistics but have real consequences for scientific principles and health recommendations. ITT analyses may answer the question of what happens when treatments are recommended but are inappropriate where separate information on adherence and performance is available. It is proposed that results of RCTs, or any experimental study, be reported, not in terms of the analyses that were performed, but rather in terms of the questions that the analyses can answer properly.
Published:
January 8, 2009
Title:
[Is there a reason to take the cholesterol campaign seriously?]
Authors:
Ravnskov, Uffe
Abstract:
Published:
January 6, 2009
Title:
Clinical Experience of a Diet Designed to Reduce Aging
Authors:
Rosedale, Ron; Westman, Eric C.; Konhilas, John P.
Abstract:
OBJECTIVE: Aging is associated with elevated levels of glucose, insulin, and triglycerides. Our objective was to assess the effect of a nutritional program designed to reduce these correlates of aging. DESIGN: This is a retrospective chart review of patients attending an outpatient metabolic management program including a high-fat, adequate-protein, low-carbohydrate diet, nutritional supplementation and periodic individual visits. Outcomes measured at baseline and follow-up included body weight, fasting serum glucose, insulin, leptin, lipids, and thyroid hormone. RESULTS: Thirty-one patients were identified with complete information. The mean age of patients was 57.6 ± 2.4 consisting of 53% female and 47% male patients. The average duration between follow up visits was 91.5 ± 8.5 days. Of the parameters measured at the follow-up visit, body weight, serum leptin, insulin, fasting glucose, triglyceride, and free T(3) significantly decreased by 8.1 ± 0.8%, 48.2 ± 3.8%, 40.1 ± 4.7%, 7.6 ± 2.1%, 28.3 ± 5.7%, and 10.8 ± 1.8%, respectively. Furthermore, the triglyceride/high density lipoprotein ratio decreased from 5.1 ± 1.7 to 2.6 ± 0.5. CONCLUSIONS: In the context of an outpatient medical clinic, a high-fat, adequate-protein, low-carbohydrate diet with nutritional supplementation led to improvements in serum factors related to the aging process. Further research regarding this dietary approach and its relationship to aging is in order.
Published:
December 31, 2008
Title:
Dental Caries in Japanese Human Skeletal Remains
Authors:
Fujita, Hisashi
Abstract:
The focus of the present study was dental carious sites in ancient Japanese skeletal remains, which has long been a focus of research. This topic is of interest because it has not received much attention. In addition, the causes of numerous incidents of root caries observed in the investigation of dental caries in ancient skeletal remains need to be examined. The results of this study indicated that there are more root caries than coronal caries in modern-day people. In Japanese people of the Edo period or earlier, the great majority of dental carious sites were on root surfaces. The cause was the loss of alveolar bone due to periodontal disease, and the cementum of the root was exposed, resulting in caries invasion of the exposed area. This sequence of events led to a pattern of dental caries and root caries in ancient Japanese people. This type of caries can be said to be of the elderly-type caries of the modern era. It is generally speculated that the advancement of physiological aging in ancient people was very rapid as they were under considerable physical stress. Unlike modern-day people, ancient people were unable to receive scientific dental treatment, and dental caries and periodontal disease were more frequent than expected. Using information gathered from investigations over many years, the historical changes in dental caries and the characteristics of dental caries in Japanese people from the Jomon period to the modern era are outlined.
Published:
December 31, 2008
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