Steven T. Chen

The Effect of Dietary Patterns on Estimated Coronary Heart Disease Risk Results From the Dietary Approaches to Stop Hypertension (DASH) Trial

Background—The Dietary Approaches to Stop Hypertension (DASH) diet is recommended in the 2005 US Dietary Guidelines. To understand the potential benefits of DASH on coronary heart disease (CHD), we applied the Framingham risk equations to calculate 10-year risk of developing CHD using data from the DASH trial. Methods and Results—In the DASH trial, 459 individuals with prehypertension or stage-1 hypertension not taking antihypertensive medication were randomly assigned to 1 of 3 diets: control, fruits and vegetables (F/V), or DASH (rich in fruits, vegetables, low-fat dairy, and reduced in fats and cholesterol). Weight was held constant. Estimated 10-year CHD risk was the primary outcome of this secondary analysis. Among 436 participants with complete data, mean (SD) age was 44.7 (10.7) years, 51% were male, and 60% were African-American. Median 10-year CHD risk was 0.98% at baseline and decreased in all groups. Compared with control, the relative risk ratio comparing 8-week with baseline 10-year CHD risk was 0.93 (95% confidence interval, 0.85 to 1.02; P=0.12) for F/V and 0.82 (95% confidence interval, 0.75 to 0.90; P<0.001) for DASH. Comparing DASH with F/V, the relative risk ratio was 0.89 (95% confidence interval, 0.81 to 0.97; P=0.012). With the exception of an interaction between dietary pattern and race suggesting a greater risk reduction in blacks than whites (P for interaction=0.038), results were similar across subgroups. Conclusions—Compared with control and F/V, the DASH diet reduced estimated 10-year CHD risk by 18% and 11%, respectively. In addition to reducing blood pressure, the DASH diet should substantially reduce the risk of CHD. Clinical Trial Registration—URL: http://clinicaltrials.gov. Unique identifier: NCT00000544.

Correlation of Apparent Diffusion Coefficient and Fractional Anisotropy Values in the Developing Infant Brain

OBJECTIVE The purpose of our study was to correlate decrease in apparent diffusion coefficient (ADC) and increase in fractional anisotropy (FA) in various white matter (WM) regions using diffusion tenor imaging (DTI) within the first year of life. MATERIALS AND METHODS We performed DTI on 53 infants and measured FA and ADC within 10 WM regions important in brain development. For each region, we calculated the slope of ADC as a function of FA, the correlation coefficient (r) and correlation of determination (r(2)). We performed a group analysis of r values and r(2)values for six WM regions primarily composed of crossing fibers and four regions primarily having parallel fibers. Upon finding that a strong correlation of FA with age existed, we adjusted for age and calculated partial correlation coefficients. RESULTS Slopes of FA versus ADC ranged from -1.00711 to -1.67592 (p < 0.05); r values ranged from -0.81 to -0.50 and r(2) values from 0.25 to 0.66. The four greatest r(2) values were within WM regions having large numbers of crossing fibers and the three lowest r(2) values were in regions having predominantly parallel fibers. After adjusting for age, slopes ranged from -1.08095 to 0.09612 (p < 0.05 in five cases); partial correlation coefficients ranged from -0.49 to 0.03 and r(2) values from 0.31 to 0.79. The highest partial correlation coefficients were then relatively equally distributed between the two types of WM regions. CONCLUSION In various regions, FA and ADC evolved with differing degrees of correlation. We found a strong influence of age on the relationship between FA and ADC.

Diffusion-Tensor Imaging Assessment of White Matter Maturation in Childhood and Adolescence

OBJECTIVE The purpose of this study was to test a first hypothesis that fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values continue to change in late childhood and adolescence and a second hypothesis that less mature white matter (WM) regions have a higher rate of change than WM regions that are relatively more mature. SUBJECTS AND METHODS Eighty-seven healthy children (50 girls, 37 boys; mean age, 11.2 ± 3.6 years; range, 4.2-17.7 years) underwent six-direction diffusion-tensor imaging with a 3-T MRI system. Three neuroradiologists independently drew regions of interest in 10 WM regions and measured FA and ADC values. To test the first hypothesis, we correlated these values with subject age by linear regression analysis (p < 0.05). To test the second hypothesis, we determined whether regions with lower FA and higher ADC in the 4- to 7-year old group had a higher slope of FA increase and ADC decrease over the entire age range. For this assessment, we used linear regression analysis (p < 0.05) and curve fitting. RESULTS In the test of the first hypothesis, increases in FA with age were noted in all WM regions and were statistically significant in six regions. Decreases in ADC values with age were noted in all brain regions except the genu of the corpus callosum. In all other regions except the splenium of the corpus callosum, the decreases were statistically significant. In the test of the second hypothesis, the relation between FA in the 4- to 7-year-old subjects and the FA increase in the entire sample was best described with a linear equation. The rate of age-related FA increase tended to be greater with lower initial FA (r = -0.384, p = 0.271). The relation between ADC in the 4- to 7-year-old subjects and ADC decrease in the entire population was best described with a second-order equation. The rate of age-related ADC decrease tended to be greater with higher initial ADC (r = 0.846, p = 0.001). For ADC values of 100 or less at age 4-7 years, the rate of ADC change with age tended to be decrease as initial ADC increased. CONCLUSION In general, both hypotheses were verified. Overall, FA values continue to increase and ADC values continue to decrease during childhood and adolescence. The most rapid changes were found in WM regions that were least mature in the first few years of the study period.

Progression of Corpus Callosum Diffusion-Tensor Imaging Values During a Period of Signal Changes Consistent With Myelination

OBJECTIVE Changes in signal intensity on T1- and T2-weighted MR images consistent with myelination in the corpus callosum occur during months 3-9 of postnatal life and occur earlier in the splenium than in the genu. We hypothesized that the rate of change in diffusion-tensor imaging parameters in the first year of life would be greater in the splenium, especially during months 3-9. SUBJECTS AND METHODS Fifty-two infants (age range, 0-52 weeks) underwent one MRI examination with a six-direction diffusion-tensor imaging sequence. Fractional anisotropy, apparent diffusion coefficient, radial diffusivity, and axial diffusivity were measured in the genu and splenium of the corpus callosum. For each parameter, the slopes of change in the splenium and in the genu were measured for the entire first year of life and for the age period 3-9 months. The ratios of slope of change in the splenium to that in the genu in these two periods were compared. RESULTS For fractional anisotropy, the ratio of slope of change in the splenium to that in the genu was 1.67 in the first year and 4.00 for 3-9 months; apparent diffusion coefficient, 2.00 in the first year and 4.33 for 3-9 months; radial diffusivity, 1.75 in the first year and 4.40 for 3-9 months; and axial diffusivity, 3.25 in the first year and 4.86 for 3-9 months. CONCLUSION Rates of change were always greater in the splenium. For the age period 3-9 months, the splenium-to-genu ratio was approximately 1.5- to 2.5-fold as high as that for the entire year. These findings correspond well with the sequence of signal intensity changes in the corpus callosum.

Severe cutaneous eruptions on telaprevir

[1] Parker HM, Johnson NA, Burdon KA, Cohn JS, OConnor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012;56:944–951. [2] Kris-Etherton PM, Harris WS, Appel LJNutrition Committee of the American Heart Association. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease [Erratum appears in Circulation 2003;107:512]. Circulation 2002;106:2747–2757.

Halo sign: Useful CT sign for differentiating benign from malignant colonic disease

AIM To evaluate the halo sign for accurately distinguishing benign from malignant colonic wall thickening. MATERIALS AND METHODS Computed tomography (CT) examinations of 92 patients (70 men; 22 women; mean age 57 years) with pathologically proven colonic wall thickening (51 benign and 41 malignant) were retrospectively reviewed in a blinded fashion. The affected segment was assessed for presence of the halo sign, degree and uniformity of thickness and density of the intramural stratum. RESULTS The halo sign was present in 74.5% (38/51) patients with benign and 7.3% (3/41) patients with malignant bowel disease. The presence of the halo sign was 75.4% sensitive and 92.5% specific for benign bowel wall thickening. All 38 benign halos showed uniform, continuous stratification; only one of three malignant halos met the strict criteria for benign halo. CONCLUSION The halo sign is a moderately sensitive and highly specific sign for distinguishing benign from malignant bowel wall thickening. However, it is not pathognomonic for benign disease. Detailed analysis of halo characteristics is necessary to improve the usefulness of this finding.

A High-Content Larval Zebrafish Brain Imaging Method for Small Molecule Drug Discovery

Drug discovery in whole-organisms such as zebrafish is a promising approach for identifying biologically-relevant lead compounds. However, high content imaging of zebrafish at cellular resolution is challenging due to the difficulty in orienting larvae en masse such that the cell type of interest is in clear view. We report the development of the multi-pose imaging method, which uses 96-well round bottom plates combined with a standard liquid handler to repose the larvae within each well multiple times, such that an image in a specific orientation can be acquired. We have validated this method in a chemo-genetic zebrafish model of dopaminergic neuron degeneration. For this purpose, we have developed an analysis pipeline that identifies the larval brain in each image and then quantifies neuronal health in CellProfiler. Our method achieves a SSMD* score of 6.96 (robust Z’-factor of 0.56) and is suitable for screening libraries up to 105 compounds in size.

Variable Response to Naltrexone in Patients With Hailey-Hailey Disease

levels of UV radiation, and the prevalence of sunburn, a biological indicator of overexposure to UV radiation, have decreased in recentyears,particularlyamongadolescentsandyoungadults.5,6 Decreases in indoor tanning and sunburn would be expected to result in decreases in melanoma incidence rates over time. Althoughprimaryskincancerpreventioneffortshaveoftenfocused on children, adolescents, and young adults, the steady increase in melanoma incidence rates among older adults indicates a need for efforts that promote skin cancer preventive behaviors throughoutadulthood.Sucheffortscouldfocusongroupsathigh risk, such as outdoor workers and intentional tanners. Ongoing surveillance of melanoma incidence is warranted to monitor progress toward national skin cancer prevention goals and guide prevention strategies.

High-throughput screening to identify potent and specific inhibitors of microbial sulfate reduction

The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

A cross-sectional survey on the attitudes, perceptions, and motivations of patients who volunteer to teach dermatology to medical students.

While areas of blood flow are usually unchanged after Wood lamp irradiation, cutaneous blood flow itself was also reported associated with activity of vitiligo lesions. Furthermore, unrecognized mechanisms must have been related considering the locations of linear streaks exactly along the superficial leg vein. From the rarity of this reaction, we postulate that this may be an idiosyncratic reaction in a genetically susceptible patient, while future studies are required. For previous cases with triamcinolone injections, hypopigmentation generally began to resolve without further treatment, several months after discontinuation of the steroid. In this case, hypopigmentation has persisted for more than 7 months even after cessation of application. Permanent hypopigmentation is an important cosmetic issue, and in this case, just application of mid potent topical steroid cream for 2 weeks caused broad linear hypopigmentation extending from the original site. This case is presented to draw the physicians’ attention to a new possible side effect observed during patients’ application of corticosteroids – one of the most widely prescribed medications in dermatology.