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Author Ross, I.; Mejia, C.; Melendez, J.; Chan, P.A.; Nunn, A.C.; Powderly, W.; Goodenberger, K.; Liu, J.; Mayer, K.H.; Patel, R.R. url  doi
openurl 
  Title Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 3 Pages e0173057  
  Keywords Adult; Anti-HIV Agents/therapeutic use; *Attitude of Health Personnel; Cross-Sectional Studies; Female; Guatemala; HIV Infections/*prevention & control; *Health Knowledge, Attitudes, Practice; Humans; Logistic Models; Male; Middle Aged; Physicians/psychology; Practice Patterns, Physicians'/*statistics & numerical data; Pre-Exposure Prophylaxis/*statistics & numerical data; Surveys and Questionnaires  
  Abstract INTRODUCTION: HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. METHODS: We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. RESULTS: Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. CONCLUSIONS: Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.  
  Address Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28257475 Approved no  
  Call Number ref @ user @ Serial 97644  
Permanent link to this record
 

 
Author Das, B.C.; Khan, A.S.; Elahi, N.E.; Uddin, M.S.; Debnath, B.C.; Khan, Z.R. url  openurl
  Title Morbidity and Mortality after Pancreatoduodenectomy: A Five Year Experience in Bangabandhu Sheikh Mujib Medical University Type Journal Article
  Year 2017 Publication Mymensingh Medical Journal : MMJ Abbreviated Journal Mymensingh Med J  
  Volume 26 Issue 1 Pages 145-153  
  Keywords  
  Abstract Mortality and morbidity was assessed after adoption of a systematic care for patient with pancreatoduodenectomy starting from patient selection and preparation, operative technique, and postoperative care. In this prospective study seventy patients who underwent pancreatoduodenectomy for periampullary carcinoma with curative intent between January 2010 and December 2014 were carefully analyzed prospectively. Patients were selected those who had ampullary carcinoma, lower bile duct carcinoma and small size carcinoma head of pancreas without local invasion and distant metastasis, and the patient who did not have any major disabling comorbid diseases. All patients were assessed uniformly before surgery and deficiency were corrected up to normal level before operation. Pancreatoduodenectomy and standard lymphadenectomy was performed meticulously with minimum blood loss. The pancreatojejunal reconstruction was performed using duct-to-mucosa method mostly. A nasojejunal feeding tube was placed in most patients for starting postoperative early oral feeding. Broad spectrum antibiotics and the epidural analgesia were mostly prescribed for good control infection and pain. Proper nutrition was maintained in calculative way through central venous line and nasojejunal feeding tube in the early postoperative period. General care, early mobilization and chest physiotherapy were given routinely in each patient. Seventy-seven percent (n=54) patients did not have any postoperative complications and they were discharged from hospital within 12-14 postoperative days. The morbidity occurred in 16 patients (23%) and most common complication was wound infection (18%, n=9). The rest complications were pancreatojejunal anastomotic leakage – 2, hepaticojejunal anastomosis leakage – 1, melaena – 1, intra-abdominal abscess – 1, intra-abdominal hemorrhage – 1, and renal dysfunction – 1. The mortality rate was 5.7% (n=4), causes of death were massive myocardial infarction; 1, failure of reversal from anesthesia; 1, massive intraabdominal bleeding; 1 and CV catheter related severe sepsis; 1. Review of recent published literature revealed that mortality and morbidity our series is better than low volume center and almost similar with high volume center of pancreatoduodenectomy surgery. Our systematic management policy of careful patient selection, planned approach in the form of proper work up, meticulous conduction of the procedure, appropriate postoperative care provides an acceptable morbidity and mortality after pancreatoduodenectomy.  
  Address Dr Bidhan C Das, Associate Professor, Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh; E-mail: dbidhan@yahoo.com  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1022-4742 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28260769 Approved no  
  Call Number ref @ user @ Serial 98727  
Permanent link to this record
 

 
Author Das, B.C.; Khan, A.S.; Elahi, N.E.; Uddin, M.S.; Debnath, B.C.; Khan, Z.R. url  openurl
  Title Morbidity and Mortality after Pancreatoduodenectomy: A Five Year Experience in Bangabandhu Sheikh Mujib Medical University Type Journal Article
  Year 2017 Publication Mymensingh Medical Journal : MMJ Abbreviated Journal Mymensingh Med J  
  Volume 26 Issue 1 Pages 145-153  
  Keywords  
  Abstract Mortality and morbidity was assessed after adoption of a systematic care for patient with pancreatoduodenectomy starting from patient selection and preparation, operative technique, and postoperative care. In this prospective study seventy patients who underwent pancreatoduodenectomy for periampullary carcinoma with curative intent between January 2010 and December 2014 were carefully analyzed prospectively. Patients were selected those who had ampullary carcinoma, lower bile duct carcinoma and small size carcinoma head of pancreas without local invasion and distant metastasis, and the patient who did not have any major disabling comorbid diseases. All patients were assessed uniformly before surgery and deficiency were corrected up to normal level before operation. Pancreatoduodenectomy and standard lymphadenectomy was performed meticulously with minimum blood loss. The pancreatojejunal reconstruction was performed using duct-to-mucosa method mostly. A nasojejunal feeding tube was placed in most patients for starting postoperative early oral feeding. Broad spectrum antibiotics and the epidural analgesia were mostly prescribed for good control infection and pain. Proper nutrition was maintained in calculative way through central venous line and nasojejunal feeding tube in the early postoperative period. General care, early mobilization and chest physiotherapy were given routinely in each patient. Seventy-seven percent (n=54) patients did not have any postoperative complications and they were discharged from hospital within 12-14 postoperative days. The morbidity occurred in 16 patients (23%) and most common complication was wound infection (18%, n=9). The rest complications were pancreatojejunal anastomotic leakage – 2, hepaticojejunal anastomosis leakage – 1, melaena – 1, intra-abdominal abscess – 1, intra-abdominal hemorrhage – 1, and renal dysfunction – 1. The mortality rate was 5.7% (n=4), causes of death were massive myocardial infarction; 1, failure of reversal from anesthesia; 1, massive intraabdominal bleeding; 1 and CV catheter related severe sepsis; 1. Review of recent published literature revealed that mortality and morbidity our series is better than low volume center and almost similar with high volume center of pancreatoduodenectomy surgery. Our systematic management policy of careful patient selection, planned approach in the form of proper work up, meticulous conduction of the procedure, appropriate postoperative care provides an acceptable morbidity and mortality after pancreatoduodenectomy.  
  Address Dr Bidhan C Das, Associate Professor, Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh; E-mail: dbidhan@yahoo.com  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1022-4742 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28260769 Approved no  
  Call Number ref @ user @ Serial 99757  
Permanent link to this record
 

 
Author Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. url  doi
openurl 
  Title Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume 17 Issue 1 Pages 178  
  Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids  
  Abstract BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.  
  Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28270132 Approved no  
  Call Number ref @ user @ Serial 96603  
Permanent link to this record
 

 
Author Celiku, O.; Tandle, A.; Chung, J.-Y.; Hewitt, S.M.; Camphausen, K.; Shankavaram, U. url  doi
openurl 
  Title Computational analysis of the mesenchymal signature landscape in gliomas Type Journal Article
  Year 2017 Publication BMC Medical Genomics Abbreviated Journal BMC Med Genomics  
  Volume 10 Issue 1 Pages 13  
  Keywords Cd44; Computational modeling; Epithelial to mesenchymal transition; Glioma  
  Abstract BACKGROUND: Epithelial to mesenchymal transition, and mimicking processes, contribute to cancer invasion and metastasis, and are known to be responsible for resistance to various therapeutic agents in many cancers. While a number of studies have proposed molecular signatures that characterize the spectrum of such transition, more work is needed to understand how the mesenchymal signature (MS) is regulated in non-epithelial cancers like gliomas, to identify markers with the most prognostic significance, and potential for therapeutic targeting. RESULTS: Computational analysis of 275 glioma samples from “The Cancer Genome Atlas” was used to identify the regulatory changes between low grade gliomas with little expression of MS, and high grade glioblastomas with high expression of MS. TF (transcription factor)-gene regulatory networks were constructed for each of the cohorts, and 5 major pathways and 118 transcription factors were identified as involved in the differential regulation of the networks. The most significant pathway – Extracellular matrix organization – was further analyzed for prognostic relevance. A 20-gene signature was identified as having prognostic significance (HR (hazard ratio) 3.2, 95% CI (confidence interval) = 1.53-8.33), after controlling for known prognostic factors (age, and glioma grade). The signature's significance was validated in an independent data set. The putative stem cell marker CD44 was biologically validated in glioma cell lines and brain tissue samples. CONCLUSIONS: Our results suggest that the differences between low grade gliomas and high grade glioblastoma are associated with differential expression of the signature genes, raising the possibility that targeting these genes might prolong survival in glioma patients.  
  Address Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 10 Center Drive, Bldg. 10, Rm. B3B70, Bethesda, MD, 20892, USA. uma@mail.nih.gov  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1755-8794 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28279210 Approved no  
  Call Number ref @ user @ Serial 96602  
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