MD, Harvard Medical School (2017)
Cost-effectiveness of earlier or more intensive colorectal cancer screening in overweight and obese patients.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Overweight and obese persons have elevated rates of colorectal cancer (CRC) but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons.We adapted our validated decision analytic model of CRC screening to compare screening starting at age 45 or 40 instead of 50, and/or shortening screening intervals, in women and men with body-mass-index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 (Colo10) or 5 years (Colo5), or annual FIT.Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I-III, reflecting the counterbalancing of higher CRC risk by lower life-expectancy as BMI rises. For all BMI/sex groups, Colo10 starting at 45 or FIT starting at 40 were cost-effective at a threshold of $100,000/quality-adjusted life year (QALY) gained. Colo10 starting at 40 was cost-effective only for men with obesity II-III, at $93,300 and $80,400/QALY gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks.CRC screening starting at age 45 with colonoscopy, or 40 with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II-III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening.
View details for DOI 10.1016/j.cgh.2022.07.028
View details for PubMedID 35940514
Visual Processing Impairments Detected by Oculometric Assessment Provide Evidence of Obesity-Related Neurological Dysfunction
NATURE PUBLISHING GROUP. 2018: S586–S587
View details for Web of Science ID 000464611002157
Reproducibility of a novel computed-tomography based measurement of renal papillary density in the Framingham Heart Study.
BMC research notes
2015; 8: 811-?
Renal papillary calcification is a compelling candidate risk factor for chronic kidney disease (CKD) and nephrolithiasis. Renal papillary density (RPD), as assessed by computed tomography (CT), is a potential marker for calcification that has not been well studied. We developed a protocol to measure RPD using CT scans and assessed its reproducibility in participants from the Framingham Heart Study.We assessed RPD of right kidneys from a single abdominal CT slice in 100 representative participants from the Framingham Heart Study (47% female, mean age 59.9 years) using a novel protocol. We selected the kidney slice with the most open sinus space and assessed RPD using the average of three 20 mm(2) ellipses from upper, middle and lower papillary regions. Two different readers performed RPD measurements and the first reader repeated all measurements to determine both intra- and inter-reader reproducibility, respectively.Of 100 total individuals included in the replication dataset, six were excluded for poor scan quality. Average RPD across all individuals was 48.7 ± 4.7 (range 38.7-61.7) Hounsfield Units (HU). The intra- and inter-reader correlation coefficients were 0.86 and 0.79, respectively. Bland-Altman analysis suggested no systematic bias between the different reads.Measuring RPD is practical and reproducible using MDCT scans from a small sample of a community-based cohort.
View details for DOI 10.1186/s13104-015-1784-6
View details for PubMedID 26695484
View details for PubMedCentralID PMC4688991
The Association Between Subcutaneous Fat Density and the Propensity to Store Fat Viscerally
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2015; 100 (8): E1056-E1064
Alterations in the cellular characteristics of subcutaneous adipose tissue (SAT) may reduce its ability to expand in times of caloric excess, increasing the propensity to store excess calories viscerally (visceral adipose tissue [VAT]). We hypothesized (1) that increased SAT density, an indirect marker of fat quality, would be associated with an increased VAT/SAT ratio and increased cardiovascular disease (CVD) risk and (2) that these associations would be independent of the absolute volume of SAT.We investigated the association of SAT density with the VAT/SAT ratio and CVD risk in 3212 participants (48% women, mean age, 50.7 years) from the Framingham Heart Study. Adipose tissue depot density and volume were quantified by computed tomography; traditional CVD risk factors were quantified.Higher SAT density was correlated with a higher VAT/SAT ratio in men (r = 0.17; P < .0001) but not in women (r = 0.04; P ≥ .05). More adverse levels of CVD risk factors were observed in the high SAT density/high VAT/SAT ratio group than in the referent group (low density/low ratio). For example, women had an increased risk of diabetes (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.6-17.6; P = .0001) and hypertension (OR, 1.6; 95% CI, 1.1-2.4; P = .009). Additional adjustment for SAT volume generally strengthened these associations (diabetes OR, 10.8; 95% CI, 4.1-29.0; hypertension OR, 2.5; 95% CI, 1.7-3.7; all P < .0001). These trends were similar but generally weaker in men.High fat density, an indirect marker of fat quality, is associated with the propensity to store fat viscerally vs subcutaneously and is jointly characterized by an increased burden of CVD risk factors.
View details for DOI 10.1210/jc.2014-4032
View details for Web of Science ID 000364855900006
View details for PubMedID 26062015
View details for PubMedCentralID PMC4525002
H2A.Z-Dependent Regulation of Cohesin Dynamics on Chromosome Arms
MOLECULAR AND CELLULAR BIOLOGY
2014; 34 (11): 2092-2104
Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are major determinants of chromosome structure and dynamics. The cohesin complex embraces sister chromatids throughout interphase, but during mitosis most cohesin is stripped from chromosome arms by early prophase, while the remaining cohesin at kinetochores is cleaved at anaphase. This two-step removal of cohesin is required for sister chromatids to separate. The cohesin-related Smc5/6 complex has been studied mostly as a determinant of DNA repair via homologous recombination. However, chromosome segregation fails in Smc5/6 null mutants or cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs in the fission yeast Schizosaccharomyces pombe following genotoxic and replication stress, or topoisomerase II dysfunction, and these mitotic defects are due to the postanaphase retention of cohesin on chromosome arms. Here we show that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe. Further, we identified the histone variant H2A.Z as a critical factor to modulate cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome integrity through accurate chromosome segregation.
View details for DOI 10.1128/MCB.00193-14
View details for Web of Science ID 000335967100015
View details for PubMedID 24687850
View details for PubMedCentralID PMC4019066
Effect of body size on expression of Manduca sexta midgut genes.
Journal of experimental zoology. Part A, Ecological genetics and physiology
2012; 317 (3): 141-151
Isometric growth of larval insect midgut predicts that the ratio of midgut surface area to body mass decreases as larvae grow. Gut tissue and gut content masses were measured in first through fifth instar Manduca sexta larvae. Wet mass of gut tissue increased in relationship to body mass with a scaling exponent of 0.85 compared to an exponent of 1.33 for gut content mass, suggesting that surface area becomes increasingly limiting in larger larvae. To test the hypothesis that compensation for the decrease in relative surface area of the midgut occurs by increased expression of membrane proteins, we compared midgut mRNA expression in fourth and fifth instar. Surveyed genes encoded apical membrane proteins with diverse functions, including the potassium amino acid transporter KAAT1, ion channel CAATCH1, aminopeptidase msAPN3, V-type H-ATPase E subunit, and cation chloride cotransporter masBSC. KAAT1 was expressed 300- to 1500-fold higher in middle and posterior midgut compared to anterior midgut. Expression of msAPN3 was approximately 200-fold higher in posterior midgut than middle midgut. Expression of KAAT1 was 2.3- to 3.1-fold higher in fifth compared to fourth-instar larvae, and masBSC expression was 1.3- to 1.9-fold higher in fifth-instar larvae. Expression of msAPN3 and V-ATPase, but not KAAT1, decreased as body mass increased within the fifth instar. Although the increased expression of KAAT1 and masBSC in fifth-instar larvae supports the hypothesis of increased membrane protein expression in larger larvae, results from the other genes do not support this hypothesis.
View details for DOI 10.1002/jez.1001
View details for PubMedID 22311716