Overview of the treatment of binge eating disorder.

We performed a qualitative review of treatment studies of binge eating disorder (BED), focusing on randomized clinical trials (RCTs). Limited effectiveness has been demonstrated for self-help strategies, and substantial effectiveness has been shown for cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT and IPT may each be more effective than behavior weight loss therapy (BWLT) for reducing binge eating over the long term. The stimulant pro-drug lisdexamfetamine dimesylate (LDX) is the only drug approved by the FDA for the treatment of BED in adults based on 2 pivotal RCTs. Topiramate also decreases binge eating behavior, but its use is limited by its adverse event profile. Antidepressants may be modestly effective over the short term for reducing binge eating behavior and comorbid depressive symptoms, but are not associated with clinically significant weight loss. A RCT presented in abstract form suggests that intranasal naloxone may decrease time spent binge eating. There is no RCT of obesity surgery in BED, but many patients with BED seek and receive such surgery. While some studies suggest patients with BED and obesity do just as well as patients with obesity alone, other studies suggest that patients with BED have more post-operative complications, less weight loss, and more weight regain. This evidence suggests that patients with BED would benefit from receiving highly individualized treatment.

Eradicating acute myeloid leukemia in a Mll(PTD/wt):Flt3(ITD/wt) murine model: a path to novel therapeutic approaches for human disease.

The coexpression of the MLL partial tandem duplication (PTD) and the FLT3 internal tandem duplication (ITD) mutations associate with a poor outcome in cytogenetically normal acute myeloid leukemia (AML). In mice, a double knock-in (dKI) of Mll(PTD/wt) and Flt3(ITD/wt) mutations induces spontaneous AML with an increase in DNA methyltransferases (Dnmt1, 3a, and 3b) and global DNA methylation index, thereby recapitulating its human AML counterpart. We determined that a regulator of Dnmts, miR-29b, is downregulated in bone marrow of dKI AML mice. Bortezomib exerted a dose-dependent increase in miR-29b expression in AML blasts ex vivo, followed by decreased Dnmts, reduced proliferation, and increased apoptosis. In vivo, bortezomib was not active against dKI AML, yet liposomal-encapsulated bortezomib, as a single agent, reversed downregulation of miR-29b in vivo and induced a long-term (90-day) disease-free remission in 80% of dKI AML mice that exhibited high leukemic burden at the start of therapy, yet showed no signs of relapse at autopsy. Taken together, these data support that liposomal bortezomib, as a single agent, eradicates Mll(PTD/wt):Flt3(ITD/wt) AML in mouse and may represent a powerful and potentially curative approach to high-risk human disease.

Proteomic analysis of the slit diaphragm complex: CLIC5 is a protein critical for podocyte morphology and function.

Podocytes are morphologically complex cells, the junctions of which form critical elements of the final filtration barrier. Disruption of their foot processes and slit diaphragms occur early in the development of many glomerular diseases. Here, we biochemically purified fractions enriched with slit diaphragm proteins and performed a proteomic analysis to identify new components of this important structure. Several known slit diaphragm proteins were found, such as podocin and nephrin, confirming the validity of the purification scheme. However, proteins on the apical membrane such as podocalyxin were neither enriched nor identified in our analysis. The chloride intracellular channel protein 5 (CLIC5), predominantly expressed in podocytes, was enriched in these fractions and localized in the foot process apical and basal membranes. CLIC5 colocalized and associated with the ezrin/radixin/moesin complex and with podocalyxin in podocytes in vivo. It is important to note that CLIC5(-/-) mice were found to have significantly decreased foot process length, widespread foot process abnormalities, and developed proteinuria. The ezrin/radixin/moesin complex and podocalyxin were significantly decreased in podocytes from CLIC5(-/-) mice. Thus, our study identifies CLIC5 as a new component that is enriched in and necessary for foot process integrity and podocyte function in vivo.

Electron-beam computerized tomography correlates with coronary angiogram in chronic kidney disease patients.

BACKGROUND/AIM: Electron-beam computerized tomography (EBCT) is able to noninvasively quantify coronary artery calcification (CAC). Chronic kidney disease (CKD) patients frequently have CAC, and clinicians are puzzled regarding the clinical significance of this finding and the diagnostic accuracy of coronary EBCT in CKD. The aim of this study was to determine the correlation in CKD patients between CAC measured by EBCT and 50% stenosis determined by coronary angiography (CA), the gold standard to identify atherosclerotic lesions. METHOD: We recruited 37 patients with CKD from a single institution and compared their coronary EBCT and CA results using standard statistical analysis. RESULTS: Patients with at least one vessel with > or = 50% stenosis by CA had higher mean CAC scores [2,407.9 +/- (SD) 3,165.3 vs. 227 +/- 443.4; p < 0.001] and higher median CAC scores (1,052 vs. 25.8; p < 0.001) as compared with those having no stenosis > or = 50%. The sensitivity was 85.7%, and the specificity 82.6% using 50% stenosis as the definition for coronary artery disease and using a CAC score of 400 as a cutoff value for the EBCT results. The area under the receiver operating characteristic curve was 0.84. The diagnostic accuracy (proportion of correct results) was 83.8%. The negative predictive value was 90.5%. The receiver operating characteristic curve suggests that the optimal cutoff value for CAC scores in our cohort is 315.9, increasing the area under the receiver operating characteristic curve to 0.91. The total coronary artery stenosis was significantly associated with the CAC score (p = 0.01). CONCLUSIONS: EBCT has a very good predictive value for obstructive coronary artery disease. EBCT could be used as a screening tool in CKD patients with a low-to-intermediate risk for coronary artery disease.

Factores fundamentales de exposición al Dengue según escenarios geoepidemiológicos en Trujillo Metropolitano. Abril-Mayo 2001 / Fundamental factors of exposure to Dengue as geoepidemiological scenarios

Objetivo: Determinar los factores fundamentales que explican las condiciones de exposición al dengue clásico en Trujillo Metropolitano, según escenarios geoepidemiológicos. Material y Métodos: Estudio descriptivo transversal, obteniendo información mediante tres instrumentos, se aplicó análisis univariado y multivariado. Resultados: Se determinó dos factores fundamentales, de intervención (vivienda intervenida, uso de abate, familias afectadas, jefe de familia con buen nivel de conocimiento, depósitos con agua tapados y vivienda con piso de tierra) y facilitador del dengue (se ha desplazado a otros distritos, floreros con larvas y viviendas con piso de tierra, llantas con larvas y malla en las ventanas). La incidencia de periodo estimada en la población estudiada fue 19.9%. El grupo etário más afectado fue el de 35 a 44 años (23%); no hubo diferencia significativa en ambos sexos; el 56.2% de casos procedieron de Florencia de Mora; según el análisis cluster, agrupa los escenarios epidemiológicos I y III. El nivel de conocimientos sobre dengue en los jefes de familia de la población encuestada en Trujillo Metropolitano fue considerado aceptable en el 8.2% y no aceptable en el 91.8%. Conclusiones: Se encontró dos factores fundamentales, de intervención y facilitador del dengue.

Objective: To identify the key factors that explains the exposure conditions to dengue fever according to geoepidemiologic settings in metropolitan Trujillo. Methods: A cross-sectional descriptive study. Information was obtained from three different instruments, univariate and multivariate analysis were made. Results: We identified two key factors, of intervention (houses intervened, use of abate, affected families, head of the family with a good level of education, covered water deposits and houses with not cement floors) and dengue´s facilitator (traveled to another other districts, vases with larvaes, houses with not cement floors, tires with larvaes and nets on the windows). The incidence of estimated period was 19.9%. The most affected age group was the 35 û 44 years old group (23%), there was no significant difference between both sexes. Fifty six percent of cases were from Florencia de Mora. According to the cluster analysis, it correspond to epidemiological scenarios I and III. The heads of families had an acceptable level of knowledge about dengue in 8.2% and not acceptable in 91.8%. Conclusions: Two key factors were found out,intervention and dengue's facilitator.