Regulation of Surgical Procedures and Health Care Facilities Rankings in Nepal

Globally, millions of surgeries are performed each year to compliment and manage a diverse set of medical conditions. Adverse surgical outcomes constitute a major proportion of avoidable death and disabilities in the hospital, especially in low-income countries like Nepal. A comprehensive study on the standards of surgical procedures and its institutional regulations is missing. We discuss here the importance of surgical regulation based on it’s financial as well as healthcare implications in the Nepalese healthcare system. Keywords: surgical procedures; health care facilities; safety; surgery; WHO.

Detection of SLA Violation for Big Data Analytics Applications in Cloud

SLA violations do happen in real world. An SLA violation represents the failure of guaranteeing a service, which leads to unwanted consequences such as penalty payments, profit margin reduction, reputation degradation, customer churn and service interruptions. Hence, in the context of cloud-hosted big data analytics applications (BDAAs), it is paramount for providers to predict and prevent SLA violations. While machine learning-based techniques have been applied to detect SLA violations for web service or general cloud service, the study on detecting SLA violations dedicated for cloud-hosted BDAAs is still lacking. In this article, we propose four machine learning techniques and integrate 12 resampling methods to detect SLA violations for batch-based BDAAs in the cloud. We evaluate the efficiency of the proposed techniques in comparison with ideal and baseline classifiers based on a real-world trace dataset (Alibaba). Our work not only helps providers to choose the best performing prediction technique, but also provides them capabilities to uncover the hidden pattern of multiple configurations of BDAAs across layers

Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

Background: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/ relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL. Methods: Fourteen AML cell lines including the DS-AMKL CMY and CMK from relapsed/refractory AML were used. Cytarabine (Ara-C), bortezomib (BTZ), disulfiram/copper (DSF/Cu2+) were evaluated for cytotoxicity, depletion of ALDH-positive cells, and resistance. BTZ-resistant CMY and CMK variants were generated by continuous BTZ treatment. Cell viability was assessed using CellTiter-Glo((R)), ALDH activity by ALDELUOR(TM), and proteasome inhibition by western blot of ubiquitinated proteins and the Proteasome-Glo(TM) Chymotrypsin-Like (CT-like) assay, apoptosis by Annexin V Fluos/Propidium iodide staining, and mutations were detected using PCR, cloning and sequencing. Results: Ara-C-resistant AML cell lines were sensitive to BTZ and DSF/Cu2+. The Ara-C-resistant DS-AMKL CMY cells had a high percentage of ALDHbright "stem-like" populations that may underlie Ara-C resistance. One percent of these cells were still resistant to BTZ but sensitive to DSF/Cu2+. To understand the mechanism of BTZ resistance, BTZ resistant (CMY-BR) and (CMK-BR) were generated. A novel mutation PSMB5 Q62P underlied BTZ resistance, and was associated with an overexpression of the beta 5 proteasome subunit. BTZ-resistance conferred increased resistance toAra-C due to G1 arrest in the CMY-BR cells, which protected the cells from S-phase damage by Ara-C. CMY-BR and CMK-BR cells were cross-resistant to CFZ and MG-132 but sensitive to DSF/Cu2+. In this setting, DSF/Cu2+ induced apoptosis and proteasome inhibition independent of CT-like activity inhibition. Conclusions: We provide evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL.St. Baldrick consortium; Children's Cancer Network; Phoenix Children's Hospital Foundation; University of Arizona Department of Child Health missionOpen Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Additional file 1: Figure S1. of Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

Structure of the PSMB5 gene and mRNA (A). DNA chromatogram showing the location of PSMB5 Q62P mutation in exon 2 (B). 3D protein structure of the PSMB5 Q62P performed using Swiss Prot database, showing the location of the PSMB5 Q62P on the alpha helix (blue arrow). A previously reported PSMB5 mutation (Cys63) is shown (C). (PPTX 419 kb

Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis

Patients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of MAP2K1/MEK1 in 50% and 25% of cases, respectively. We evaluated a patient with treatment-refractory LCH for mutations in the RAS-RAF-MEK-ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto-activating. During treatment with the MEK inhibitor trametinib, the patient's disease showed significant progression. In vitro characterization of the MAP2K1 p.L98_K104 > Q deletion confirmed its effect on cellular activation of the ERK pathway and drug resistance.Sharon D. Lund Foundation; University of Arizona COM-P Department of Child Health Mission Support; Phoenix Children's Hospital Foundation12 month embargo; first published: 16 May 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]