Rapid-Onset Obesity, Hypothalamic Dysregulation, Hypoventilation, Autonomic Dysregulation, and Neuroendocrine Tumour: Rare Syndrome with Myriad Anaesthesia Implications.

Anaesthesia management of a child with rapid-onset obesity, hyperphagia, and hypothalamic dysfunction syndrome is complex due to the multisystem involvement, the most important features being morbid obesity, autonomic dysfunction, and dyselectrolytemia due to hypothalamic dysfunction. The acronym of the disease was amended in 2008 to rapid-onset obesity, hyperphagia, hypothalamic dysfunction neural crest tumour to include the risk of ganglioneuroma or ganglioneuroblastoma. Patients usually require removal of tumour in the prone position. Obstructive sleep apnea, difficult airway and intravenous access, and haemodynamic lability all add to the trials faced by the paediatric anaesthesiologist. Invasive haemodynamic monitoring, ultrasonography, bispectral index monitoring, and meticulous calculation of drug dosages help in smoothening the course of anaesthesia in the presence of constant vigilance.

Discovery of a Potent and Selective PI3Kδ Inhibitor (S)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy in Hematological Cancer Models.

PI3Kδ inhibitors have been approved for B-cell malignancies like CLL, small lymphocytic lymphoma, and so forth. However, currently available PI3Kδ inhibitors are nonoptimal, showing weakness against at least one of the several important properties: potency, isoform selectivity, and/or pharmacokinetic profile. To come up with a PI3Kδ inhibitor that overcomes all these deficiencies, a pharmacophoric expansion strategy was employed. Herein, we describe a systematic transformation of a "three-blade propeller" shaped lead, 2,3-disubstituted quinolizinone 11, through a 1,2-disubstituted quinolizinone 20 to a novel "four-blade propeller" shaped 1,2,3-trisubstituted quinolizinone 34. Compound 34 has excellent potency, isoform selectivity, metabolic stability across species, and exhibited a favorable pharmacokinetic profile. Compound 34 also demonstrated a differentiated efficacy profile in human germinal center B and activated B cell-DLBCL cell lines and xenograft models. Compound 34 qualifies for further evaluation as a candidate for monotherapy or in combination with other targeted agents in DLBCLs and other forms of iNHL.

Knowledge and attitude of women regarding breast cancer screening tests in Eastern Iran.

INTRODUCTION: According to recent statistics, there has been a rapid growth of breast cancer in developing countries. Thus, early detection is essential. This study is based on the perception of people in the Northeast of Iran regarding breast cancer screening. METHODS: In a cross-sectional study, 1469 women were selected randomly in the period from April to November 2016. The study population consisted of women or their companions referring to outpatient clinics or people in public urban areas who filled out a breast cancer screening questionnaire in an interview. RESULTS: The patients' age was in the range of 14 to 84 years (mean = 38.8). More than 84% of interviewees were not informed of breast cancer and screening tests. The main reasons mentioned by patients for their failure to do screening tests was 'absence of any symptom or problem' and 'they did not think it was necessary'.There was not a significant difference between income level, marital status and knowledge of people about breast cancer screening tests (P > 0.05). However, employment, education level and family history had a positive effect on people's awareness of breast cancer and its screening tests (P < 0.05). CONCLUSION: The lack of knowledge in people from low socio-economic classes was the main barrier to breast cancer screening. In this regard, organizing training programs by physicians and the media can help raise screening rates.