Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: A randomized controlled trial

Background/objectives: Owing to excess body weight and increased secretion of inflammatory cytokines primarily during the third trimester, pregnancy is associated with elevated insulin resistance. To our knowledge, no report is available indicating the effects of probiotic yoghurt consumption on serum insulin levels in pregnant women. This study was designed to determine the effects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women. Subjects/methods: In this randomized controlled clinical trial, 70 primigravida pregnant women with singleton pregnancy at their third trimester were participated. We randomly assigned participants to consume 200 g per day of conventional (n=33) or the probiotic group (n=37) for 9 weeks. The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus, enriched with probiotic culture of two strains of lactobacilli (Lactobacillus acidophilus LA5) and bifidobacteria (Bifidobacterium animalis BB12) with a total of min 1 � 10 7 colony-forming units. Fasting blood samples were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance score. Results: Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score, significant differences were found comparing changes in these variables between probiotic and conventional yogurts (changes from baseline in serum insulin levels: +1.2±1.2 vs +5.0±1.1 μIU/ml, respectively, P=0.02; and in HOMA-IR score: -0.2±0.3 vs 0.7±0.2, respectively, P=0.01). Conclusions: It is concluded that in contrast to conventional yogurt, daily consumption of probiotic yogurt for 9 weeks maintains serum insulin levels and might help pregnant women prevent developing insulin resistance. © 2013 Macmillan Publishers Limited

Neospora caninum and Leishmania infantum Co-Infection in Domestic Dogs (Canis familiaris) in Meshkin-Shahr District, Northwestern Iran

Background: Mediterranean visceral leishmaniasis (MVL)is an infectious disease that affects both human and ani­mals. Domestic dogs (Canis familiaris) are principal reservoir hosts of MVL caused by Leishmania infantum. Dogs are definitive hosts for Neospora caninumand a risk factor for infecting intermediate hosts. The immunosuppression caused by visceral leishmaniasis (VL) can promote the occurrence of co-infections with other agents such as neosporo­sis. This study aimed to determine the frequency of co-infection of the both protozoan parasites in the en­demic areas of VL from Meshkin-Shahr District, north-west of Iran. Methods: Altogether, 171 serum samples were collected from domestic dogs of Meshkin- Shahr District by multistage cluster sampling from October 2008 to August 2009. The collected serum samples were tested for the detection of simultaneous infection of L. infantum and N. caninum using direct agglutination test (DAT) and indirect ELISA, respectively. Results: Of the 171 domestic dogs, 27 (15.8%) and 52 (30.4%) were showed antibodies against L. infantum and N. caninum, respectively. Simultaneous infections of N. caninum and L. infantum was found in 16 (9.4%) of the dogs. In VL-positive and VL-negative dogs, N. caninum infection was found in 59.3% and 25.0%, respectively. A statisti­cally significant difference was found between VL-positive and VL-negative dogs with N. caninum infection (P= 0.001). Conclusion: These findings indicate that Meshkin-Shahr District in northwestern Iran is an active focus of canine visceral leishmaniasis (CVL). Neospora caninum and L. infantum co-infection is prevalent in the area and infection by L. infantum seems to enhance susceptibility to N. caninum infection in domestic dogs

Design and implementation of an empowerment model to prevent elder abuse: a randomized controlled trial

Fatemeh Estebsari,1 Maryam Dastoorpoor,2 Davoud Mostafaei,3 Narges Khanjani,4 Zahra Rahimi Khalifehkandi,5 Abbas Rahimi Foroushani,6 Hamidreza Aghababaeian,7 Mohammad Hossein Taghdisi8 1Department of Community Health Nursing, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, 2Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 3Department of Nursing Management, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, 4Neurology Research Center, Kerman University of Medical Sciences, Kerman, 5Department of Health Education and Health Promotion, School of Health, Iran University of Medical Sciences, Tehran, 6Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, 7Nursing and Emergency Department, Dezful University of Medical Sciences, Dezful, 8Department of Health Education and Health Promotion, School of Health, Iran University of Medical Sciences, Tehran, Iran Background: Older adults are more vulnerable to health risks than younger people and may get exposed to various dangers, including elder abuse. This study aimed to design and implement an empowerment educational intervention to prevent elder abuse.Methods: This parallel randomized controlled trial was conducted in 2014–2016 for 18 months on 464 older adults aged above 60 years who visited health houses of 22 municipalities in Tehran. Data were collected using standard questionnaires, including the Elder Abuse-Knowledge Questionnaire, Health-Promoting Behavior Questionnaire, Health-Promoting Lifestyle Profile II, Barriers to Healthy Lifestyle, Perceived Social Support, Perceived Self-Efficacy, Loneliness Scale, Geriatric Depression Scale, Multidimensional Health Locus of Control Scale, and the SCARED (stress, coping, argument, resources, events, and dependence) tool. The intervention was done in twenty 45- to 60-minute training sessions over 6 months. Data analysis were performed using χ2 tests, multiple linear and logistic regression, and structural equation modeling (SEM).Results: The frequency of knowledge of elder abuse, self-efficacy, social support and health promoting lifestyle before the intervention was similar in the two groups. However, the frequency of high knowledge of elder abuse (94.8% in the intervention group and 46.6% in the control group), high self-efficacy (82.8% and 7.8%, respectively), high social support (97.0% and 10.3%, respectively) and high health promoting lifestyle (97.0% and 10.3%, respectively) was significantly higher (P<0.001) and the frequency of elder abuse risk (28.0% and 49.6%, respectively) was significantly less in the intervention group after the intervention. SEM standardized beta (Sβ) showed that the intervention had the highest impact on increase social support (Sβ=0.80, β=48.64, SE=1.70, P<0.05), self-efficacy (Sβ=0.76, β=13.32, SE=0.52, P<0.05) and health promoting behaviors (Sβ=0.48, β=33.08, SE=2.26, P<0.05), respectively. The effect of the intervention on decrease of elder abuse risk was indirect and significant (Sβ=-0.406, β=-0.340, SE=0.03, P<0.05), and through social support, self-efficacy, and health promoting behaviors.Conclusion: Educational interventions can be effective in preventing elder abuse. Keywords: elder abuse, self-efficacy, social support, health promotion, health educatio

A comparative evaluation of regulatory T cells profile among acute and chronic cutaneous leishmaniasis using flow cytometry

Background: Cutaneous leishmaniasis (CL) is described as a major health problem in many countries of the world. Regulatory T cells (Tregs) are characterized as one of immunologic indexes. One of the best methods to determine of Tregs percentage is flow cytometry. The aim of this study was determination of the role of Tregs profile among acute and chronic forms of human CL using flow cytometry analysis. Methods: This study was conducted on 24 patients referred to Laboratory of Leishmaniasis, Tehran University of Medical Sciences, Tehran, Iran with acute and 14 patients with chronic phases of CL as well as 15 healthy individuals as control group in 2015-2016. After microscopic examination, 2 ml of peripheral blood samples were collected for determining percentage of CD4 + CD25+ CD127 low Tregs by using flow cytometry method. Results: Using flow cytometry analysis, the average percentage of Tregs were calculated 5.73, 6.71 and 6.61 for acute, chronic and healthy individuals, respectively. With SPSS software and Scheffe multiple comparison tests, the differences within in these groups are statistically significant (P=0.04) and between the acute and chronic group, there was marginally significant with approximately 91 of confidence level (P=0.088). Conclusion: Marginally differences were found significantly among averages of Regulatory T cells, acute and chronic phases of CL. Further comprehensive studies can be needed to verify the role of Tregs in both phases of CL cases. © 2019, Tehran University of Medical Sciences (TUMS). All rights reserved