Tuberculosis posses a major threat for health practitioners due to lengthy treatment regimen, increase in the drug-resistant strains of Mycobacterium tuberculosis (M. tb) and unavailability of drugs for its persistent form. Therefore, there is an urgent need for discovery of new and improved anti-tubercular drugs. In M. tb, the two step de novo biosynthesis of L-cysteine, an essential metabolic pathway is reported to be up-regulated in the persistent phase of the organism, involves two enzymes CysE and CysK. Although, structural insights for rational drug discovery are available for the later, not much information is known for the former. This study proposes a 3-dimensional model of M. tb CysE followed by in-silico screening of 67,030 anti-tuberculosis bioactive compounds.  https://www.selleckchem.com/products/GDC-0449.html  Subsequently, post-processing of 1000 best hits was carried out and top 200 compounds thus obtained were docked into the active site cleft of E. coli homologue as a control, but revealed unexpected results. Differences in the active site architectures and comparative analysis of molecular electrostatic potentials between the two CysEs provide molecular basis for the compounds C1, C3, C4 and C7 exhibiting preferential binding for M. tb CysE. In addition, shorter N-terminus along with positive and irregular trimeric base of M. tb CysE indicates its biological assembly as trimer. Based on mapping of residues involved in cysteine sensitivity on to the model structure of M. tb CysE, it is hypothesized that feedback inhibition of this homologue by cysteine may be affected.Communicated by Ramaswamy H. Sarma.The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, rendering EZH2 to be an attractive target for the treatment of PBRM1 frequently mutated cancers. In the current study, we combined computational and biochemical approaches to establish an efficient system for the screening and validation of synthetic lethal inhibitors from a large pool of chemical compounds. Five putative EZH2 inhibitors were identified through structure-based virtual screening from 47,737 chemical compounds and analyzed with molecular dynamics. The efficacy of these compounds against EZH2 was tested using PBRM1 deficient and wide-type cell lines. The compound L501-1669 selectively inhibited the proliferation of PBRM1-deficient cells and down-regulated the tri-methylation of histone H3 at Lysine 27 (H3K27me3). Importantly, we also observed an increase in apoptotic activities in L501-1669 treated PBRM1-deficient cells. Taken together, our results demonstrate that L501-1669 is a selective EZH2 inhibitor with promising application in the targeted therapy of PBRM1-deficient cancers.OBJECTIVE To examine the effects of the extent of endoscopic sinus surgery (ESS) on pulmonary health, including the pulmonary exacerbations and lung function in patients with cystic fibrosis (CF). STUDY DESIGN Retrospective cohort study. SETTING Tertiary health care center. SUBJECTS AND METHODS A retrospective review of patients with CF who underwent ESS at St. Michael's Hospital between 1999 and 2016 was performed. Two groups of patients were identified based on the surgical extent (1) complete (maxillary antrostomy, complete ethmoidectomy, sphenoidotomy, and frontal sinusotomy) and (2) limited (any ESS that involved less than complete). Primary outcomes included the number of pulmonary exacerbations (the use of oral or intravenous [IV] antibiotics), number of hospital admissions and hospital days during a 2-year pre- and postoperative period, and pulmonary function outcomes during a 1-year pre- and postoperative period. RESULTS There were 70 procedures (30 complete and 40 limited) among 57 patients. Baseline characteristics were similar between the groups. Complete ESS group had a significant reduction in the oral antibiotic use compared to the limited ESS group (median, -1.0 [interquartile range (IQR), -2 to 0] in complete vs 0 [IQR, -1 to 1] in limited, P = .028). There was no difference in the use of IV antibiotics, number and duration of admissions, or rate of lung function change between the 2 groups. CONCLUSION Complete ESS may reduce mild forms of pulmonary exacerbations as shown in the decreased use of oral antibiotics. Overall, ESS does not significantly modify pulmonary outcomes in patients with CF.This article reviews the collaboration between clinician and illustrator throughout the ages while highlighting the era of cardiac surgery. Historical notes are based on Professor Sanjib Kumar Ghosh's extensive review, literature searches, and the archives of the Johns Hopkins University Department of Art as related to Medicine in Baltimore. Personal communications were explored with medical illustrators and medical practitioners, many of whom are colleagues and trainees, to further chronicle the history of medical illustration and education in the era of cardiac surgery. Medical illustrators use their talents and expressive ideas to demonstrate procedures and give them life. These methods are (1) hovering technique; (2) hidden anatomy, ghosted views, or transparency; (3) centrally focused perspective; (4) action techniques to give life to the procedure; (5) use of insets to highlight one part of the drawing; (6) human proportionality using hands or known objects to show size; and (7) step-by-step educational process to depict the stages of a procedure. Vivid examples showing these techniques are demonstrated. The result of this observational analysis underscores the importance of the collaboration between clinician and illustrator to accurately describe intricate pathoanatomy, three-dimensional interrelated anatomic detail, and complex operations. While there are few data to measure the impact of the atlas on medical education, it is an undeniable assertion that anatomical and surgical illustrations have helped to educate and train the modern-day surgeon, cardiologist, and related health-care professionals.BACKGROUND The presence of echocardiographic (echo) evidence is a major criterion for the diagnosis of infective endocarditis (IE) by modified Duke criteria. Pulmonary valve (PV) IE, however, can be challenging to identify by echo. We sought to evaluate the added utility of multimodal imaging in PV IE. METHODS This is a single-center case series. We retrospectively analyzed demographic, laboratory, imaging, clinical, and surgical data from patients diagnosed with PV IE from 2008 to 2018. RESULTS A total of 23 patients were identified with definite PV IE by Duke criteria (83% male and ages 2 months to 70 years). Twenty-two patients had congenital heart disease, with 21 involving the right ventricular outflow tract (including three with transcatheter PV implant). Overall, 20 (87%) of 23 had positive blood cultures. A total of 17 (74%) of 23 patients demonstrated echo evidence of PV IE. In three cases, echo was negative (did not show vegetations) but showed new PV obstruction. In four cases with negative transthoracic echocardiogram and transesophageal echocardiogram, evidence of PV IE was subsequently seen by positron emission tomography/computed tomography (n = 2) or cardiac magnetic resonance imaging (n = 2).