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Background: Prevalence of type 2 diabetes (T2D) is rising, and its burden on the healthcare system remains a challenge. Consumption of a plant-predominant diet is a promising approach for achieving remission, which has emerged as a therapeutic target. Objective: To establish feasibility of achieving T2D remission with a plant-predominant diet in a cohort of free-living individuals. Methods: Patients referred to a wellness clinic were treated with a low-fat, whole food, plant-predominant diet while receiving standard medical treatment. Included patients were adults, mostly elderly, with HbA1c > 6.5%, with or without use of antidiabetic medications. Results: N = 59 patients were included in this analysis, with mean age 71.5 years (range 41-89). Twenty-two (37%) patients achieved T2D remission. Mean differences showed a significant decrease post-lifestyle change (T2) compared to prior to lifestyle change (T1) for the following outcomes [least squares mean difference (95% CI)]: BMI [-2.6 (-4.8, -.3)] kg/m 2 ; HbA1c [ -1.3 (-1.6, -1.0)] %; and fasting glucose [-29.6 (-41.8, -17.5)] mg/dL. No significant differences were observed for systolic or diastolic blood pressure, HDL, LDL, or triglycerides. Conclusion: A lifestyle-based treatment intervention promoting adherence to a plant-predominant diet and integrated as part of routine care can successfully achieve T2D remission in wellness clinic patients., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Panigrahi and Ms. Goodwin are employees of the Wellness Clinic described in the manuscript. Dr. Karlsen and Ms. Staffier are employees of the American College of Lifestyle Medicine., (Copyright © 2023 The Author(s).)

Aim: To determine whether 4 months of rivastigmine treatment would result in metabolic changes and whether metabolic changes correlate with changes in cognition in people with Alzheimer's disease (AD)., Methods: Magnetic resonance spectra were acquired from the posterior cingulate cortex of subjects with AD at 3 T. Magnetic resonance imaging scans and cognitive tests were performed before and 4 months after the beginning of the treatment. Metabolite concentrations were quantified and used to calculate the metabolite ratios., Results: On average, the N-acetylaspartate/creatine (NAA/Cr) ratio decreased by 12.7% following 4 months of rivastigmine treatment, but changes in the NAA/Cr ratio correlated positively with changes in Mini-Mental State Examination scores., Conclusion: This positive correlation between changes in NAA/Cr and changes in cognitive performance suggests that the NAA/Cr ratio could be an objective indicator of a response to rivastigmine treatment., (© 2014 S. Karger AG, Basel)

Importance: Bariatric surgery is a well-documented treatment for obesity, but there are uncertainties about the degree to which such surgery is associated with health care cost reductions that are sustained over time., Objective: To provide a comprehensive, multiyear analysis of health care costs by type of procedure within a large cohort of privately insured persons who underwent bariatric surgery compared with a matched nonsurgical cohort., Design: Longitudinal analysis of 2002-2008 claims data comparing a bariatric surgery cohort with a matched nonsurgical cohort., Setting: Seven BlueCross BlueShield health insurance plans with a total enrollment of more than 18 million persons., Participants: A total of 29 820 plan members who underwent bariatric surgery between January 1, 2002, and December 31, 2008, and a 1:1 matched comparison group of persons not undergoing surgery but with diagnoses closely associated with obesity., Main Outcome Measures: Standardized costs (overall and by type of care) and adjusted ratios of the surgical group's costs relative to those of the comparison group., Results: Total costs were greater in the bariatric surgery group during the second and third years following surgery but were similar in the later years. However, the bariatric group's prescription and office visit costs were lower and their inpatient costs were higher. Those undergoing laparoscopic surgery had lower costs in the first few years after surgery, but these differences did not persist., Conclusions and Relevance: Bariatric surgery does not reduce overall health care costs in the long term. Also, there is no evidence that any one type of surgery is more likely to reduce long-term health care costs. To assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings.

Background: Bariatric surgery is the most effective weight loss treatment, yet few studies have reported on short- and long-term outcomes postsurgery., Methods: Using claims data from seven Blue Cross/Blue Shield health plans serving seven states, we conducted a non-concurrent, matched cohort study. We followed 22,693 persons who underwent bariatric surgery during 2003-2007 and were enrolled at least 6 months before and after surgery. Using logistic regression, we compared serious and less serious adverse clinical outcomes, hospitalizations, planned procedures, and obesity-related co-morbidities between groups for up to 5 years., Results: Relative to controls, surgery patients were more likely to experience a serious [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.8-2.0] or less serious (OR 2.5, CI 2.4-2.7) adverse clinical outcome or hospitalization (OR 1.3, CI 1.3-1.4) at 1 year postsurgery. The risk remained elevated until 4 years postsurgery for serious events and 5 years for less serious outcomes and hospitalizations. Some complication rates were lower for patients undergoing laparoscopic surgery. Planned procedures, such as skin reduction, peaked in postsurgery year 2 but remained elevated through year 5. Surgery patients had a 55% decreased risk of obesity-related co-morbidities, such as type 2 diabetes, in the first year postsurgery, which remained low throughout the study (year 5: OR 0.4, CI 0.4-0.5)., Conclusions: While bariatric surgery is associated with a higher risk of adverse clinical outcomes compared to controls, it also substantially decreased obesity-related co-morbidities during the 5-year follow-up.

Background: Section 4104 of the Patient Protection and Affordable Care Act (ACA) waives previous cost-sharing requirements for many Medicare-covered preventive services. In 1997, Congress passed similar legislation waiving the deductible only for mammograms and Pap smears. The purpose of this study is to examine the effect of the deductible waiver on mammogram and Pap smear utilization rates., Methods: Using 1995-2003 Medicare claims from a sample of female, elderly Medicare fee-for-service beneficiaries, two pre/post analyses were conducted comparing mammogram and Pap smear utilization rates before and after implementation of the deductible waiver. Receipt of screening mammograms and Pap smears served as the outcome measures, and two time measures, representing two post-test observation periods, were used to examine the short- and long-term impacts on utilization., Results: There was a 20 percent short-term and a 25 percent longer term increase in the probability of having had a mammogram in the four years following the 1997 deductible waiver. Beneficiaries were no more likely to receive a Pap smear following the deductible waiver., Conclusions: Elimination of cost sharing may be an effective strategy for increasing preventive service use, but the impact could depend on the characteristics of the procedure, its cost, and the disease and populations it targets. These historical findings suggest that, with implementation of Section 4104, the greatest increases in utilization will be seen for preventive services that screen for diseases with high incidence or prevalence rates that increase with age, that are expensive, and that are performed on a frequent basis.

Background: Disturbance in the metabolism of tryptophan and tryptophan-derived compounds (e.g., melatonin) may have a role in the pathogenesis of delirium., Objective: To evaluate the efficacy of low dose exogenous melatonin in decreasing delirium., Design: A randomized, double-blinded, placebo-controlled study., Setting: An Internal Medicine service in a tertiary care centre in London, Ontario, Canada., Participants: 145 individuals aged 65 years or over admitted through the emergency department to a medical unit in a tertiary care hospital., Intervention: Patients were randomized to receive either 0.5 mg of melatonin or placebo every night for 14 days or until discharge., Measurements: The primary outcome was the occurrence of delirium as determined by Confusion Assessment Method (CAM) criteria., Results: Of a total of 145 individuals (mean age (standard deviation): 84.5 (6.1) years) 72 were randomly assigned to the melatonin group and 73 to the placebo group. Melatonin was associated with a lower risk of delirium (12.0% vs. 31.0%, p = 0.014), with an odds ratio (OR), adjusted for dementia and co-morbidities of 0.19 (95% confidence intervals (CI): 0.06-0.62). Results were not different when patients with prevalent delirium were excluded., Limitation: An intention to treat analysis was not possible due to loss to follow-up., Conclusion: Exogenous low dose melatonin administered nightly to elderly patients admitted to acute care may represent a potential protective agent against delirium., (Copyright © 2010 John Wiley & Sons, Ltd.)

Obesity is underdiagnosed, hampering system-based health promotion and research. Our objective was to develop and validate a claims-based risk model to identify obese persons using medical diagnosis and prescription records. We conducted a cross-sectional analysis of de-identified claims data from enrollees of 3 Blue Cross Blue Shield plans who completed a health risk assessment capturing height and weight. The final sample of 71,057 enrollees was randomly split into 2 subsamples for development and validation of the obesity risk model. Using the Johns Hopkins Adjusted Clinical Groups case-mix/predictive risk methodology, we categorized study members' diagnosis (ICD) codes. Logistic regression was used to determine which claims-based risk markers were associated with a body mass index (BMI) > or = 35 kg/m(2). The sensitivities of the scores > or =90(th) percentile to detect obesity were 26% to 33%, while the specificities were >90%. The areas under the receiver operator curve ranged from 0.67 to 0.73. In contrast, a diagnosis of obesity or an obesity medication alone had very poor sensitivity (10% and 1%, respectively); the obesity risk model identified an additional 22% of obese members. Varying the percentile cut-point from the 70(th) to the 99(th) percentile resulted in positive predictive values ranging from 15.5 to 59.2. An obesity risk score was highly specific for detecting a BMI > or = 35 kg/m(2) and substantially increased the detection of obese members beyond a provider-coded obesity diagnosis or medication claim. This model could be used for obesity care management and health promotion or for obesity-related research.

Objective. The purpose of this study was to examine whether neighborhood- and individual-level characteristics affect providers' likelihood of providing an obesity diagnosis code in their obese patients' claims. Methods. Logistic regressions were performed with obesity diagnosis code serving as the outcome variable and neighborhood characteristics and member characteristics serving as the independent variables (N = 16,151 obese plan members). Results. Only 7.7 percent of obese plan members had an obesity diagnosis code listed in their claims. Members living in neighborhoods with the largest proportions of Blacks were 29 percent less likely to receive an obesity diagnosis (P < .05). The odds of having an obesity diagnosis code were greater among members who were female, aged 44 or below, hypertensive, dyslipidemic, BMI >/= 35 kg/m(2), had a larger number of provider visits, or who lived in an urban area (all P < .05). Conclusions. Most health care providers do not include an obesity diagnosis code in their obese patients' claims. Rates of obesity identification were strongly related to individual characteristics and somewhat associated with neighborhood characteristics.

Several prescription medications are approved to treat obesity, yet little is known about their use in the United States. Our objective was to describe recent trends and patterns of obesity reduction medication use in an insured US population. From among ~4.2 million persons enrolled in two Blue Cross and Blue Shield plans, we obtained all medical and pharmacy claims for 86,804 persons who took an obesity reduction medication anytime during 2002-2005. Overall, obesity reduction medication use decreased significantly over time from 1% in 2002 to 0.7% in 2005 (P for trend <0.001), which was most notable for the newer medications (orlistat and sibutramine). Few (range: 11-18%) used these medications longer than 3 months regardless of whether they were Federal Drug Administration (FDA)-approved for long-term use or not. More than half (57%) of obesity reduction medication users also took narcotics and 38% took antidepressants. Few sympathomimetic users had potential serious contraindications prior to medication initiation, including cardiovascular diseases (2.4%), schizophrenia (2.5%), and age >65 (1.2%). Despite the high prevalence of obesity, obesity reduction medication use was low and decreased significantly from 2002 through 2005. Prescribers of these agents should be aware of approved durations, potential contraindications, and consider screening for depression and substance abuse.

The softening of fleshy fruits, such as tomato (Solanum lycopersicum), during ripening is generally reported to result principally from disassembly of the primary cell wall and middle lamella. However, unsuccessful attempts to prolong fruit firmness by suppressing the expression of a range of wall-modifying proteins in transgenic tomato fruits do not support such a simple model. 'Delayed Fruit Deterioration' (DFD) is a previously unreported tomato cultivar that provides a unique opportunity to assess the contribution of wall metabolism to fruit firmness, since DFD fruits exhibit minimal softening but undergo otherwise normal ripening, unlike all known nonsoftening tomato mutants reported to date. Wall disassembly, reduced intercellular adhesion, and the expression of genes associated with wall degradation were similar in DFD fruit and those of the normally softening 'Ailsa Craig'. However, ripening DFD fruit showed minimal transpirational water loss and substantially elevated cellular turgor. This allowed an evaluation of the relative contribution and timing of wall disassembly and water loss to fruit softening, which suggested that both processes have a critical influence. Biochemical and biomechanical analyses identified several unusual features of DFD cuticles and the data indicate that, as with wall metabolism, changes in cuticle composition and architecture are an integral and regulated part of the ripening program. A model is proposed in which the cuticle affects the softening of intact tomato fruit both directly, by providing a physical support, and indirectly, by regulating water status.

A novel, affinity-augmented, bacterial spore-imprinted, bead material was synthesized, based on a procedure developed for vegetative bacteria. The imprinted beads were intended as a front-end spore capture/concentration stage of an integrated biological detection system. Our approach involved embedding bead surfaces with Bacillus thuringiensis kurstaki (Bt) spores (as a surrogate for Bacillus anthracis) during synthesis. Subsequent steps involved lithographic deactivation using a perfluoroether; spore removal to create imprint sites; and coating imprints with the lectin, concanavalin A, to provide general affinity. The synthesis of the intended material with the desired imprints was verified by scanning electron and confocal laser-scanning microscopy. The material was evaluated using spore-binding assays with either Bt or Bacillus subtilis (Bs) spores. The binding assays indicated strong spore-binding capability and a robust imprinting effect that accounted for 25% additional binding over non-imprinted controls. The binding assay results also indicated that further refinement of the surface deactivation procedure would enhance the performance of the imprinted substrate.

Insertional mutagenesis of Arabidopsis (Arabidopsis thaliana) was used to identify a novel recessive mutant, designated resurrection1 (rst1), which possesses a dramatic alteration in its cuticular waxes and produces shrunken nonviable seeds due to arrested embryo development. The RST1 gene sequence associated with these phenotypes was verified by three independent, allelic, insertion mutants, designated rst1-1, rst1-2, and rst1-3, with inserts in the first exon, 12th intron, and fourth exon, respectively. These three rst1 allelic mutants have nearly identical alterations in their wax profiles and embryo development. Compared to wild type, the wax on rst1 inflorescence stems is reduced nearly 60% in total amount, has a proportional reduction in aldehydes and aldehyde metabolites, and has a proportional increase in acids, primary alcohols, and esters. Compared to wild type, the C(29) alkanes on rst1 are nearly 6-fold lower, and the C(30) primary alcohols are 4-fold higher. These results indicate that rst1 causes shunting of most wax precursors away from alkane synthesis and into the primary-alcohol-producing branch of the pathway. In contrast to stems, the wax on rst1 mutant leaves increased roughly 43% in amount relative to the wild type, with the major increase occurring in the C(31) and C(33) alkanes. Unique among known wax mutants, approximately 70% of rst1 seeds are shrunken and nonviable, with these being randomly distributed within both inflorescence and silique. Viable seeds of rst1 are slightly larger than those of wild type, and although the viable rst1 seeds contain more total triacylglycerol-derived fatty acids, the proportions of these fatty acids are not significantly different from wild type. Shrunken seeds contain 34% of the fatty acids of wild-type seeds, with proportionally more palmitic, stearic, and oleic acids, and less of the longer and more desaturated homologs. Histological analysis of aborted rst1 seeds revealed that embryo development terminates at the approximate heart-shaped stage, whereas viable rst1 and wild-type embryos develop similarly. The RST1 gene encodes a predicted 1,841-amino acid novel protein with a molecular mass of 203.6 kD and a theoretical pI of 6.21. The RST1 transcript was found in all tissues examined including leaves, flowers, roots, stems, and siliques, but accumulation levels were not correlated with the degree to which different organs appeared affected by the mutation. The new RST1 gene reveals a novel genetic connection between lipid synthesis and embryo development; however, RST1's exact role is still quite unknown. The degree to which RST1 is associated with lipid signaling in development is an important focus of ongoing studies.

To shed new light on gene involvement in plant cuticular-wax production, 11 eceriferum (cer) mutants of Arabidopsis having dramatic alterations in wax composition of inflorescence stems were used to create 14 double cer mutants each with two homozygous recessive cer loci. A comprehensive analysis of stem waxes on these double mutants revealed unexpected CER gene interactions and new ideas about individual CER gene functions. Five of the 14 double cer mutants produced significantly more total wax than one of their respective cer parents, indicating from a genetic standpoint a partial bypassing (or complementation) of one cer mutation by the other. Eight of the 14 double cer mutants had alkane amounts lower than both respective cer parents, suggesting that most of these CER gene products play a major additive role in alkane synthesis. Other results suggested that some CER genes function in more than one step of the wax pathway, including those associated with sequential steps in acyl-CoA elongation. Surprisingly, complete epistasis was not observed for any of the cer gene combinations tested. Significant overlap or redundancy of genetic operations thus appears to be a central feature of wax metabolism. Future studies of CER gene product function, as well as the utilization of CER genes for crop improvement, must now account for the complex gene interactions described here.

Pseudomonas syringae relies on type III secretion system to deliver effector proteins into the host cell for parasitism. Type III genes are induced in planta, but host factors affecting the induction are poorly understood. Here we report on the identification of an Arabidopsis mutant, att1 (for aberrant induction of type three genes), that greatly enhances the expression of bacterial type III genes avrPto and hrpL. att1 plants display enhanced disease severity to a virulent strain of P. syringae, suggesting a role of ATT1 in disease resistance. ATT1 encodes CYP86A2, a cytochrome P450 monooxygenase catalyzing fatty acid oxidation. The cutin content is reduced to 30% in att1, indicating that CYP86A2 plays a major role in the biosynthesis of extracellular lipids. att1 has a loose cuticle membrane ultrastructure and shows increased permeability to water vapor, demonstrating the importance of the cuticle membrane in controlling water loss. The enhanced avrPto-luc expression is specific to att1, but not another cuticle mutant, wax2. The results suggest that certain cutin-related fatty acids synthesized by CYP86A2 may repress bacterial type III gene expression in the intercellular spaces.

Salt cress (Thellungiella halophila) is a small winter annual crucifer with a short life cycle. It has a small genome (about 2 x Arabidopsis) with high sequence identity (average 92%) with Arabidopsis, and can be genetically transformed by the simple floral dip procedure. It is capable of copious seed production. Salt cress is an extremophile native to harsh environments and can reproduce after exposure to extreme salinity (500 mm NaCl) or cold to -15 degrees C. It is a typical halophyte that accumulates NaCl at controlled rates and also dramatic levels of Pro (>150 mm) during exposure to high salinity. Stomata of salt cress are distributed on the leaf surface at higher density, but are less open than the stomata of Arabidopsis and respond to salt stress by closing more tightly. Leaves of salt cress are more succulent-like, have a second layer of palisade mesophyll cells, and are frequently shed during extreme salt stress. Roots of salt cress develop both an extra endodermis and cortex cell layer compared to Arabidopsis. Salt cress, although salt and cold tolerant, is not exceptionally tolerant of soil desiccation. We have isolated several ethyl methanesulfonate mutants of salt cress that have reduced salinity tolerance, which provide evidence that salt tolerance in this halophyte can be significantly affected by individual genetic loci. Analysis of salt cress expressed sequence tags provides evidence for the presence of paralogs, missing in the Arabidopsis genome, and for genes with abiotic stress-relevant functions. Hybridizations of salt cress RNA targets to an Arabidopsis whole-genome oligonucleotide array indicate that commonly stress-associated transcripts are expressed at a noticeably higher level in unstressed salt cress plants and are induced rapidly under stress. Efficient transformation of salt cress allows for simple gene exchange between Arabidopsis and salt cress. In addition, the generation of T-DNA-tagged mutant collections of salt cress, already in progress, will open the door to a new era of forward and reverse genetic studies of extremophile plant biology.

Insertional mutagenesis of Arabidopsis ecotype C24 was used to identify a novel mutant, designated wax2, that had alterations in both cuticle membrane and cuticular waxes. Arabidopsis mutants with altered cuticle membrane have not been reported previously. Compared with the wild type, the cuticle membrane of wax2 stems weighed 20.2% less, and when viewed using electron microscopy, it was 36.4% thicker, less opaque, and structurally disorganized. The total wax amount on wax2 leaves and stems was reduced by >78% and showed proportional deficiencies in the aldehydes, alkanes, secondary alcohols, and ketones, with increased acids, primary alcohols, and esters. Besides altered cuticle membranes, wax2 displayed postgenital fusion between aerial organs (especially in flower buds), reduced fertility under low humidity, increased epidermal permeability, and a reduction in stomatal index on adaxial and abaxial leaf surfaces. Thus, wax2 reveals a potential role for the cuticle as a suppressor of postgenital fusion and epidermal diffusion and as a mediator of both fertility and the development of epidermal architecture (via effects on stomatal index). The cloned WAX2 gene (verified by three independent allelic insertion mutants with identical phenotypes) codes for a predicted 632-amino acid integral membrane protein with a molecular mass of 72.3 kD and a theoretical pI of 8.78. WAX2 has six transmembrane domains, a His-rich diiron binding region at the N-terminal region, and a large soluble C-terminal domain. The N-terminal portion of WAX2 is homologous with members of the sterol desaturase family, whereas the C terminus of WAX2 is most similar to members of the short-chain dehydrogenase/reductase family. WAX2 has 32% identity to CER1, a protein required for wax production but not for cuticle membrane production. Based on these analyses, we predict that WAX2 has a metabolic function associated with both cuticle membrane and wax synthesis. These studies provide new insight into the genetics and biochemistry of plant cuticle production and elucidate new associations between the cuticle and diverse aspects of plant development.

Floral volatiles, which are small and generally water-insoluble, must move from their intracellular sites of synthesis through the outermost cuticle membrane before release from the flower surface. To determine whether petal cuticle might influence volatile emissions, we performed the first analysis of petal cuticle development and its association with the emission of flower volatiles using Antirrhinum majus L. (snapdragon) as a model system. Petal cuticular wax amount and composition, cuticle thickness and ultrastructure, and the amounts of internal and emitted methylbenzoate (the major snapdragon floral scent compound) were examined during 12 days, from flower opening to senescence. Normal (n-) alkanes were found to be the major wax class of snapdragon petals (29.0% to 34.3%) throughout the 12 days examined. Besides n-alkanes, snapdragon petals possessed significant amounts of methyl branched alkanes (23.6-27.8%) and hydroxy esters (12.0-14.0%). Hydroxy esters have not been previously reported in plants. Changes in amount of methylbenzoate inside the petals followed closely with levels of methylbenzoate emission, suggesting that snapdragon petal cuticle may provide little diffusive resistance to volatile emissions. Moreover, clear associations did not exist between methylbenzoate emission and the cuticle properties examined during development. Nevertheless, the unique wax composition of snapdragon petal cuticles shows similarities with those of other highly permeable cuticles, suggesting an adaptation that could permit rapid volatile emission by scented flowers.

The Secretary's Advisory Committee on Genetic Testing (SACGT) was established by the U.S. Secretary of Health and Human Services, Donna E. Shalala, to provide a public forum for the formulation of policy advice in the complex and growing area of genetic testing. After a careful nomination and selection process, the Secretary announced the appointment of thirteen advisors to the SACGT in June 1999. The first meeting of the SACGT was held June 30, 1999. This article describes the purpose, formation, and function of the SACGT. Before addressing these questions about the role of the SACGT, we first will explain what genetic testing is, how it is currently used, and what new uses it may be put to in the future.

The postreceptor signaling pathway(s) that mediates the effects of transforming growth factor-beta1 (TGF-beta1) is incompletely understood. The present study investigated the involvement of protein kinase C (PKC) in the growth-inhibitory action of TGF-beta1 in PC3, a human prostate cancer cell line. PKC alpha, the only conventional PKC isoform detected in PC3 cells, appeared to be constitutively active based on its presence in both Triton-soluble membrane fraction and cytosol. However, levels of membrane-associated PKC alpha were decreased by a growth-inhibitory dose of TGF-beta1. The response to TGF-beta1 was rapid (within 5 min), time dependent, isoform specific, and occurred without apparent changes in levels of total PKC alpha protein. TGF-beta1 also decreased the levels of membrane-associated PKC activity coincident with its inhibitory effect on PKC alpha's membrane association. Inhibition of PKC activity appeared to be associated with growth inhibition in PC3 cells, because chelerythrine (a specific PKC inhibitor) likewise decreased cell proliferation. Taken together, our data suggest that inhibition of PKC activity, at least in part due to inactivation of PKC alpha, is an early event associated with TGF-beta1 postreceptor signaling that might mediate suppression of cell proliferation.