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2.  Exploring Triacylglycerol Biosynthetic Pathway in Developing Seeds of Chia (Salvia hispanica L.): A Transcriptomic Approach 
PLoS ONE  2015;10(4):e0123580.
Chia (Salvia hispanica L.), a member of the mint family (Lamiaceae), is a rediscovered crop with great importance in health and nutrition and is also the highest known terrestrial plant source of heart-healthy omega-3 fatty acid, alpha linolenic acid (ALA). At present, there is no public genomic information or database available for this crop, hindering research on its genetic improvement through genomics-assisted breeding programs. The first comprehensive analysis of the global transcriptome profile of developing Salvia hispanica L. seeds, with special reference to lipid biosynthesis is presented in this study. RNA from five different stages of seed development was extracted and sequenced separately using the Illumina GAIIx platform. De novo assembly of processed reads in the pooled transcriptome using Trinity yielded 76,014 transcripts. The total transcript length was 66,944,462 bases (66.9 Mb), with an average length of approximately 880 bases. In the molecular functions category of Gene Ontology (GO) terms, ATP binding and nucleotide binding were found to be the most abundant and in the biological processes category, the metabolic process and the regulation of transcription-DNA-dependent and oxidation-reduction process were abundant. From the EuKaryotic Orthologous Groups of proteins (KOG) classification, the major category was “Metabolism” (31.97%), of which the most prominent class was ‘carbohydrate metabolism and transport’ (5.81% of total KOG classifications) followed by ‘secondary metabolite biosynthesis transport and catabolism’ (5.34%) and ‘lipid metabolism’ (4.57%). A majority of the candidate genes involved in lipid biosynthesis and oil accumulation were identified. Furthermore, 5596 simple sequence repeats (SSRs) were identified. The transcriptome data was further validated through confirmative PCR and qRT-PCR for select lipid genes. Our study provides insight into the complex transcriptome and will contribute to further genome-wide research and understanding of chia. The identified novel UniGenes will facilitate gene discovery and creation of genomic resource for this crop.
PMCID: PMC4395390  PMID: 25875809
3.  BMJ Endgames: A New Web-Based BMJ/JGIM Collaboration 
PMCID: PMC3930788  PMID: 24395105
4.  The Innovator’s DNA and Health Care Improvement 
PMCID: PMC3889935  PMID: 24309951
5.  Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life 
Metabolic brain disease  2013;28(4):10.1007/s11011-013-9437-8.
Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished proliferation and maturation of stem-like cells in the hypothalamus (3rd ventricular region) as well as in the cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.
PMCID: PMC3828054  PMID: 24043569
Maternal obesity; High fat diet; Fetal brain cellular development; Hypothalamic appetite regulation
6.  Developmental programming in skeletal muscle in response to overnourishment in the immediate postnatal life in rats☆,☆☆,★ 
Overnourishment during the suckling period (small litter, SL) results in the development of adult-onset obesity. To investigate the mechanisms that underlie the development of insulin resistance in the skeletal muscle of young and adult female SL rats, the litter size was reduced to 3 female pups/dam (SL) while the control litter (CL) had 12 pups/dam from the postnatal day 3 until day 21. Protein content, mRNA expression and methylation status of the promoter region of key components in the insulin signaling pathway were determined in the skeletal muscle of SL rats. Overnutrition during the suckling period resulted in increased body weight gains, hyperphagia and adult-onset obesity as well as increased levels of serum insulin, glucose, and leptin in SL rats. No differences in the expression of total protein as well as tyrosine phosphorylation of insulin receptor β and glucose transporter 4 (GLUT4) were observed in skeletal muscle between two groups at both ages. A significant decrease of total insulin receptor substrate 1(IRS-1) and an increase in serine phosphorylation of IRS-1 were observed in skeletal muscle from adult SL rats. Hypermethylation of specific CpG dinucleotides in the proximal promoter region was observed for the Irs1 and Glut4 genes which correlated with the reduction in Irs1 and Glut4 mRNA levels in skeletal muscle of adult SL rats. Our results suggest that epigenetic modifications of the key genes involved in the insulin signaling pathway in skeletal muscle could result in the development of insulin resistance in SL female rats.
PMCID: PMC3805821  PMID: 23968580
Early overnutrition; Hyperinsulinemia; Epigenetics; DNA methylation; Insulin receptor substrate 1
7.  Disruptive and Deliberate Innovations in Healthcare 
Journal of General Internal Medicine  2013;28(9):1117-1118.
PMCID: PMC3744287  PMID: 23903988
8.  The Elusive SIRS Diagnosis 
PMCID: PMC3579969  PMID: 23054916
subacute illness; diagnostic reasoning; endocarditis; culture negative endocarditis; Nocardia; brain abscess; diagnostic delays
9.  Innovation and Inauguration 
PMCID: PMC3539024  PMID: 23242866
11.  Discussing Uncertainty and Risk in Primary Care: Recommendations of a Multi-Disciplinary Panel Regarding Communication Around Prostate Cancer Screening 
Journal of General Internal Medicine  2013;28(11):1410-1419.
Shared decision making improves value-concordant decision-making around prostate cancer screening (PrCS). Yet, PrCS discussions remain complex, challenging and often emotional for physicians and average-risk men.
In July 2011, the Centers for Disease Control and Prevention convened a multidisciplinary expert panel to identify priorities for funding agencies and development groups to promote evidence-based, value-concordant decisions between men at average risk for prostate cancer and their physicians.
Two-day multidisciplinary expert panel in Atlanta, Georgia, with structured discussions and formal consensus processes.
Sixteen panelists represented diverse specialties (primary care, medical oncology, urology), disciplines (sociology, communication, medical education, clinical epidemiology) and market sectors (patient advocacy groups, Federal funding agencies, guideline-development organizations).
Panelists used guiding interactional and evaluation models to identify and rate strategies that might improve PrCS discussions and decisions for physicians, patients and health systems/society. Efficacy was defined as the likelihood of each strategy to impact outcomes. Effort was defined as the relative amount of effort to develop, implement and sustain the strategy. Each strategy was rated (1–7 scale; 7 = maximum) using group process software (ThinkTankTM). For each group, intervention strategies were grouped as financial/regulatory, educational, communication or attitudinal levers. For each strategy, barriers were identified.
Highly ranked strategies to improve value-concordant shared decision-making (SDM) included: changing outpatient clinic visit reimbursement to reward SDM; development of evidence-based, technology-assisted, point-of-service tools for physicians and patients; reframing confusing prostate cancer screening messages; providing pre-visit decision support interventions; utilizing electronic health records to promote benchmarking/best practices; providing additional training for physicians around value-concordant decision-making; and using re-accreditation to promote training.
Conference outcomes present an expert consensus of strategies likely to improve value-concordant prostate cancer screening decisions. In addition, the methodology used to obtain agreement provides a model of successful collaboration around this and future controversial cancer screening issues, which may be of interest to funding agencies, educators and policy makers.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-013-2419-z) contains supplementary material, which is available to authorized users.
PMCID: PMC3797347  PMID: 23649782
prostate cancer screening; men’s health; shared decision-making; communication; funding priorities; risk
12.  From the Editors’ Desk: Hippocrates and Patient-centered Medicine 
PMCID: PMC3270232  PMID: 22187116
13.  From the Editors’ Desk: Valuing Health and Primary Care 
PMCID: PMC3157516  PMID: 21786079
14.  Metabolic Programming in the Immediate Postnatal Life 
Annals of Nutrition & Metabolism  2011;58(Suppl 2):18-28.
The metabolic programming effects of nutritional modifications in the immediate postnatal life are increasingly recognized to independently contribute to the development of metabolic syndrome in later life. Adjustment of litter size in rodents has been used to induce either under- or overnourishment in the immediate postnatal life of the offspring. While undernourishment led to growth retardation in the offspring, overnourishment produced increased body weight gains, hyperinsulinemia and hyperleptinemia. Overnourishment during the suckling period induced several adaptations in the energy circuitry in the hypothalamus of the offspring predisposing them for the onset of obesity later in life. Another approach for a nutritional modification in the immediate postnatal period is the artificial rearing of newborn rat pups on a high-carbohydrate (HC) milk formula without changes in the total calorie availability. Hyperinsulinemia, immediately evident in the HC pups, persisted in the post-weaning period even after withdrawal of the HC milk. Significant alterations in pancreatic islets supported chronic hyperinsulinemia in the HC rats. Alterations in the gene expression of hypothalamic neuropeptides predisposing to hyperphagia were evident during the period of the HC dietary modification. The persistence of these hypothalamic adaptations supported the obese phenotype in adult HC rats. A transgenerational effect gave rise to the development of chronic hyperinsulinemia and adult-onset obesity in the offspring of the HC female rats. Other studies have shown that lactation by a diabetic, obese or malnourished mother resulted in predisposition for the onset of metabolic disorders in the offspring. These observations from animal studies on the metabolic programming effects due to altered nutritional experiences in the immediate postnatal life strongly suggest that altered feeding practices for infants (formula feeding and early introduction of infant foods) could contribute to the rising incidence of overweight/obesity in children and adults.
PMCID: PMC3190171  PMID: 21846978
Hyperinsulinemia; Hyperphagia; Hypothalamic energy homeostasis; Increased carbohydrate intake; Nutritional experiences; Obesity; Overnourishment; Suckling period
16.  The Validity of Peer Review in a General Medicine Journal 
PLoS ONE  2011;6(7):e22475.
All the opinions in this article are those of the authors and should not be construed to reflect, in any way, those of the Department of Veterans Affairs.
Our study purpose was to assess the predictive validity of reviewer quality ratings and editorial decisions in a general medicine journal.
Submissions to the Journal of General Internal Medicine (JGIM) between July 2004 and June 2005 were included. We abstracted JGIM peer review quality ratings, verified the publication status of all articles and calculated an impact factor for published articles (Rw) by dividing the 3-year citation rate by the average for this group of papers; an Rw>1 indicates a greater than average impact.
Of 507 submissions, 128 (25%) were published in JGIM, 331 rejected (128 with review) and 48 were either not resubmitted after revision was requested or were withdrawn by the author. Of 331 rejections, 243 were published elsewhere. Articles published in JGIM had a higher citation rate than those published elsewhere (Rw: 1.6 vs. 1.1, p = 0.002). Reviewer quality ratings of article quality had good internal consistency and reviewer recommendations markedly influenced publication decisions. There was no quality rating cutpoint that accurately distinguished high from low impact articles. There was a stepwise increase in Rw for articles rejected without review, rejected after review or accepted by JGIM (Rw 0.60 vs. 0.87 vs. 1.56, p<0.0005). However, there was low agreement between reviewers for quality ratings and publication recommendations. The editorial publication decision accurately discriminated high and low impact articles in 68% of submissions. We found evidence of better accuracy with a greater number of reviewers.
The peer review process largely succeeds in selecting high impact articles and dispatching lower impact ones, but the process is far from perfect. While the inter-rater reliability between individual reviewers is low, the accuracy of sorting is improved with a greater number of reviewers.
PMCID: PMC3143147  PMID: 21799867
17.  It’s Not Behçet’s! 
PMCID: PMC3077480  PMID: 21116869
Erythema multiforme; Behçet’s syndrome; Stevens-Johnson disease
18.  Don’t Hold Your Breath 
PMCID: PMC3043171  PMID: 21104037
cribriform; ethmoid sinus fractures; meningocele; normal intracranial pressures; Valsalva maneuvers
19.  From the Editor’s Desk: Legislating Change 
PMCID: PMC2839330  PMID: 20162374
20.  Medicare Financing of Graduate Medical Education 
The past decade has seen ongoing debate regarding federal support of graduate medical education, with numerous proposals for reform. Several critical problems with the current mechanism are evident on reviewing graduate medical education (GME) funding issues from the perspectives of key stakeholders. These problems include the following: substantial interinstitutional and interspecialty variations in per-resident payment amounts; teaching costs that have not been recalibrated since 1983; no consistent control by physician educators over direct medical education (DME) funds; and institutional DME payments unrelated to actual expenditures for resident education or to program outcomes. None of the current GME reform proposals adequately address all of these issues. Accordingly, we recommend several fundamental changes in Medicare GME support. We propose a re-analysis of the true direct costs of resident training (with appropriate adjustment for local market factors) to rectify the myriad problems with per-resident payments. We propose that Medicare DME funds go to the physician organization providing resident instruction, keeping DME payments separate from the operating revenues of teaching hospitals. To ensure financial accountability, we propose that institutions must maintain budgets and report expenditures for each GME program. To establish educational accountability, Residency Review Committees should establish objective, annually measurable standards for GME program performance; programs that consistently fail to meet these minimum standards should lose discretion over GME funds. These reforms will solve several long-standing, vexing problems in Medicare GME funding, but will also uncover the extent of undersupport of GME by most other health care payers. Ultimately, successful reform of GME financing will require “all-payer” support.
PMCID: PMC1495035  PMID: 11972725
graduate medical education; internship and residency; Medicare; teaching costs; teaching hospitals
21.  Early Introduction of an Evidence-based Medicine Course to Preclinical Medical Students 
Evidence-based Medicine (EBM) has been increasingly integrated into medical education curricula. Using an observational research design, we evaluated the feasibility of introducing a 1-month problem-based EBM course for 139 first-year medical students at a large university center. We assessed program performance through the use of a web-based curricular component and practice exam, final examination scores, student satisfaction surveys, and a faculty questionnaire. Students demonstrated active involvement in learning EBM and ability to use EBM principles. Facilitators felt that students performed well and compared favorably with residents whom they had supervised in the past year. Both faculty and students were satisfied with the EBM course. To our knowledge, this is the first report to demonstrate that early introduction of EBM principles as a short course to preclinical medical students is feasible and practical.
PMCID: PMC1494995  PMID: 11903776
evidence-based medicine; preclinical medical students; web-based curriculum; problem-based learning; medical education

Results 1-21 (21)