Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice.

Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

Associations Between NIH Funding and Advanced Bibliometric Indices Among Radiological Investigators.

RATIONALE AND OBJECTIVES: Whereas data support the h index (reflecting both publications and citations) as an indicator of academic productivity, other advanced bibliometric indices aiming to address shortcomings of the h index remain poorly studied. Our objective was to compare the associations between bibliometric indices and total National Institutes of Health (NIH) grant funding among investigators within U.S. academic radiology departments. MATERIALS AND METHODS: NIH grant funding amounts for 400 NIH-funded investigators within radiology departments were obtained from Blue Ridge Institute for Medical Research. Investigators' publications and associated citations were identified using Scopus. Indices computed for each investigator included: publication count, citation count, h index, i-10 index, hc index (h index adjusted for recency of publications), m quotient (h index adjusted for career duration), and e index and g index (both account for highly cited articles). Spearman correlations were performed between indices and funding. Multivariable linear regression was performed to identify significant independent predictors of funding. RESULTS: For MD investigators: the indices exhibited no-to-weak correlations with funding (r = 0.173-0.387); m quotient exhibited the largest correlation and was the only significant (albeit weak) independent predictor of funding (P = 0.011). For PhD investigators: correlation with funding was weak for m quotient (r = 0.323), although moderate for other indices (r = 0.518-0.568); publication count exhibited highest correlation; publication count (P < 0.001) and hc index (P = 0.024) were significant independent predictors of funding. CONCLUSIONS: Bibliometric indices were more strongly associated with grant funding for PhD than for MD radiology investigators, with publication count exhibiting the strongest association in the latter group. Time-weighted adjustments, as reflected by the m quotient and hc index, may improve efforts to predict funding using bibliometrics.

Associations Between Academic Rank and Advanced Bibliometric Indices Among United States Academic Radiologists.

RATIONALE AND OBJECTIVES: This study aimed to evaluate associations between traditional and advanced bibliometric indices with academic rank for radiologists in the United States. METHODS: Faculty web pages were searched to classify 538 members of the Association of University Radiologists as assistant (n = 212), associate (n = 128), or full (n = 198) professors. Radiologists' publication and citation records were extracted from Scopus to compute the following indices: publication count, citation count, h-index, i-10 index, hc-index, m-quotient, e-index, and g-index. Analysis of variance, multivariable logistic regression, and receiver operating characteristic curve analysis were performed. RESULTS: All indices were significantly different among the three groups (P ≤.001), progressively increasing with increasing rank (eg, mean publication count of 17, 41, and 128 among assistant, associate, and full professors, respectively; mean citation count of 205, 687, and 3622, respectively; mean h-index of 5, 11, and 27, respectively). At multivariable analysis, the h-index (reflecting publications and citations) was a strong significant independent positive predictor of associate (ß=+0.32, P <.001) or full professor (ß=+0.26, P <.001) status, whereas the m-quotient (adjusted h-index that is greater for more rapid publication) was a strong significant independent negative predictor of associate (ß=-1.87, P = .009) or full professor (ß =-4.97, P <.001) status. The models exhibited moderate goodness-of-fit (r2 = 0.534-0.655; P <.001). The model for predicting at least associate professor achieved area under the curve 0.876 (sensitivity 74.6%, specificity 88.8%). The model for predicting full professor achieved area under the curve 0.925 (sensitivity 85.5%, specificity 86.1%). CONCLUSION: When controlling for the h-index, more rapid publication, as indicated by the m-quotient, was negatively associated with radiologists' academic rank, indicating the additional influence of career duration in promotions decisions.

Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance.

STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) and loop diuretic resistance. DESIGN: Retrospective cohort study. SETTING: Large urban academic medical center. PATIENTS: Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 ± 1517.4 ml versus 1397.6 ± 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. CONCLUSION: Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population.