Endoanal MRI of the anal sphincter complex: correlation with cross-sectional anatomy and histology

The purpose of this study was to correlate the in vivo endoanal MRI findings of the anal sphincter with the cross-sectional anatomy and histology. Fourteen patients with rectal tumours were examined with a rigid endoanal MR coil before undergoing abdominoperineal resection. In addition, 12 cadavers were used to obtain cross-sectional anatomical sections. The images were correlated with the histology and anatomy of the resected rectal specimens as well as with the cross-sectional anatomical sections of the 12 cadavers. The findings in 8 patients, 11 rectal preparations, and 10 cadavers, could be compared. In these cases, there was an excellent correlation between endoanal MRI and the cross-sectional cadaver anatomy and histology. With endoanal MRI, all muscle layers of the anal canal wall, comprising the internal anal sphincter, longitudinal muscle, the external anal sphincter and the puborectalis muscle wer

Ten Simple Rules for Responsible Big Data Research

The use of big data research methods has grown tremendously over the past five years in both academia and industry. As the size and complexity of available datasets has grown, so too have the ethical questions raised by big data research. These questions become increasingly urgent as data and research agendas move well beyond those typical of the computational and natural sciences, to more directly address sensitive aspects of human behavior, interaction, and health. The tools of big data research are increasingly woven into our daily lives, including mining digital medical records for scientific and economic insights, mapping relationships via social media, capturing individuals’ speech and action via sensors, tracking movement across space, shaping police and security policy via “predictive policing,” and much more

Severe Bioprosthetic Mitral Valve Stenosis and Heart Failure in a Young Woman with Systemic Lupus Erythematosus

A 23-year-old African American woman with a past medical history of systemic lupus erythematous (SLE), secondary hypertension, and end stage renal disease (ESRD) on hemodialysis for eight years was stable until she developed symptomatic severe mitral regurgitation with preserved ejection fraction. She underwent a bioprosthetic mitral valve replacement (MVR) at outside hospital. However, within a year of her surgery, she presented to our hospital with NYHA class IV symptoms. She was treated for heart failure but in view of her persistent symptoms and low EF was considered for heart and kidney transplant. This was a challenge in view of her history of lupus. We presumed that her stenosis of bioprosthetic valve was secondary to lupus and renal disease. We hypothesized that her low ejection fraction was secondary to mitral stenosis and potentially reversible. We performed a dobutamine stress echocardiogram, which revealed an improved ejection fraction to more than 50% and confirmed preserved inotropic contractile reserve of her myocardium. Based on this finding, she underwent a metallic mitral valve and tricuspid valve replacement. Following surgery, her symptoms completely resolved. This case highlights the pathophysiology of lupus causing stenosis of prosthetic valves and low ejection cardiomyopathy

Morphine Use in the ED and Outcomes of Patients With Acute Heart Failure A Propensity Score-Matching Analysis Based on the EAHFE Registry

OBJECTIVE: The objective was to determine the relationship between short-term mortality and intravenous morphine use in ED patients who received a diagnosis of acute heart failure (AHF). METHODS: Consecutive patients with AHF presenting to 34 Spanish EDs from 2011 to 2014 were eligible for inclusion. The subjects were divided into those with (M) or without IV morphine treatment (WOM) groups during ED stay. The primary outcome was 30-day all-cause mortality, and secondary outcomes were mortality at different intermediate time points, in-hospital mortality, and length of hospital stay. We generated a propensity score to match the M and WOM groups that were 1:1 according to 46 different epidemiological, baseline, clinical, and therapeutic factors. We investigated independent risk factors for 30-day mortality in patients receiving morphine. RESULTS: We included 6,516 patients (mean age, 81 [SD, 10] years; 56% women): 416 (6.4%) in the M and 6,100 (93.6%) in the WOM group. Overall, 635 (9.7%; M, 26.7%; WOM, 8.6%) died by day 30. After propensity score matching, 275 paired patients constituted each group. Patients receiving morphine had a higher 30-day mortality (55 [20.0%] vs 35 [12.7%] deaths; hazard ratio, 1.66; 95% CI, 1.09-2.54; P=.017). In patients receiving morphine, death was directly related to glycemia (P=.013) and inversely related to the baseline Barthel index and systolic BP (P=.021) at ED arrival (P=.021). Mortality was increased at every intermediate time point, although the greatest risk was at the shortest time (at 3 days: 22 [8.0%] vs 7 [2.5%] deaths; OR, 3.33; 95% CI, 1.40-7.93; P=.014). In-hospital mortality did not increase (39 [14.2%] vs 26 [9.1%] deaths; OR, 1.65; 95% CI, 0.97-2.82; P=.083) and LOS did not differ between groups (median [interquartile range] in M, 8 [7]; WOM, 8 [6]; P=.79). CONCLUSIONS: This propensity score-matched analysis suggests that the use of IV morphine in AHF could be associated with increased 30-day mortality.Peer reviewe

Distinguishing mechanisms underlying EMT tristability

Abstract Background The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models – ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done. Results Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2. Conclusions These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes

Isoflavone glycosides: Synthesis and evaluation as α-glucosidase inhibitors

On the basis of the structure of 4′,7,8-trihydroxyisoflavone 7-O-α-D-arabinofuranoside (namely A-76202, 1), a Rhodococcus metabolite showing potent inhibitory activities against the α-glucosidases of rat liver microsome (IC 50 = 0.46 ng/mL), 26 analogs, each with minor variations at the sugar moiety and the isoflavone A and B rings, were readily synthesized. Notably, a new and efficient method was developed for the divergent synthesis of the B-ring congeners of the isoflavone glycosides by using Suzuki-Miyaura coupling as the final step. Modifications at the sugar moiety and the isoflavone A ring significantly diminish the activity, whereas variations at the B ring are largely tolerated for retaining the potent α-glucosidase inhibitory activity. © Wiley-VCH Verlag GmbH & Co. KGaA, 2008.postprin

Buybacks in Treasury Cash and Debt Management

This paper examines the use of buybacks in Treasury cash and debt management. We review the mechanics and results of the buyback operations conducted in 2000-01, during a time of budget surpluses, and assess the prospective use of buybacks in the absence of a surplus. Possible future applications include (i) managing the liquidity of the new-issue markets when deficits are declining (by allowing Treasury officials to postpone a decision to discontinue a series without also being compelled to shrink new-issue sizes); (ii) actively promoting the liquidity of the new-issue markets (by repurchasing outstanding debt on a regular basis and funding the purchases with larger offerings of new debt); (iii) limiting the accumulation of large Treasury cash balances (for example, in the second half of April and early May, when many taxpayers make final payments of taxes on income earned in the prior year); and (iv) smoothing week-to-week fluctuations in Treasury bill offerings

Meltzer's History of the Federal Reserve

This review argues that Allan Meltzer's account of the Fed. between 1913-1951 complements Friedman and Schwartz's in their Monetary History. Meltzer emphasises policy making within the System, rather than the evolution of the money supply and its effects on the economy. He stresses the uncertainty of the Fed's independence before the 1951 Accord, and the effects of economic ideas, notably the real bills and Riefler-Burgess doctrines, on policy. Many virtues in the book are noted, and one weakness, a failure to explain why inadequate ideas became dominant within the Fed when sounder alternatives were available in contemporary monetary thought

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease

Effects on short term outcome of non-invasive ventilation use in the emergency department to treat patients with acute heart failure: A propensity score-based analysis of the EAHFE Registry

Objective: To assess the effects of non-invasive ventilation (NIV) in emergency department (ED) patients with acute heart failure (AHF) on short term outcomes. Methods: Patients from the EAHFE Registry (a multicenter, observational, multipurpose, cohort-designed database including consecutive AHF patients in 41 Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV–groups). Using propensity score (PS) methodology, we identified two subgroups of patients matched by 38 covariates and compared regarding 30-day survival (primary outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy, chronic obstructive pulmonary disease, AHF precipitated by an acute coronary syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE), and systolic blood pressure (SBP). Secondary outcomes were intensive care unit (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality; and prolonged hospitalization (>7 days). Results: Of 11, 152 patients from the EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a higher 30-day mortality (HR = 2.229; 95%CI = 1.861–2.670) (p 85 years, p < 0.001), AHF associated with ACS (p = 0.045), and SBP < 100 mmHg (p < 0.001). No significant differences were found in the secondary endpoints except for more prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122–1.862) (p = 0.004). Conclusion: The use of NIV to treat AHF in ED is not associated with improved mortality outcomes and should be cautious in old patients and those with ACS and hypotension