Variations in coronary artery diameter: a retrospective observational study in Indian population

Objective: The diameter of coronary arteries varies greatly among general population. The knowledge of variations in coronary arteries helps the clinicians to define abnormalities and plan the treatment. Hence, the present study was aimed to study common primary variations of coronary arteries by angiography in Indian population. Methods: The data for this unicenter, retrospective, observational study was collected from general hospital, Maharashtra, as patient data sheets and coronary angiograms (CAG) reports for a period of 1 year and 8 months. The CAG were studied for variations in main trunk diameter of coronary arteries and range of diameters of coronary arteries. Results: A total of 400 conventional CAGs were observed, of which 17 angiograms showed anatomical variations. The diameter of left coronary artery was more than right coronary artery (RCA) in 90.5% and less in 9.5% of CAGs. Statistically significant difference was observed on comparing the mean diameter of RCA (3.40(0.81 mm) and left coronary artery (4.52(0.95 mm; p<0.001). The range of diameter of RCA (1.8 to 6.2 mm) and left coronary artery differed significantly (2 to 7.3 mm; p <0.001). Conclusion: From the results, it was evident that the diameter of left coronary artery was larger than right coronary artery in majority of CAGs

Potentials of airborne hyperspectral aviris-ng data in the exploration of base metal deposit—a study in the parts of Bhilwara, Rajasthan

In this study, we have processed the spectral bands of airborne hyperspectral data of Advanced Visible Infrared Imaging Spectrometer-Next Generation (AVIRIS-NG) data for delineating the surface signatures associated with the base metal mineralization in the Pur-Banera area in the Bhilwara district, Rajasthan, India.The primaryhost rocks of the Cu, Pb, Zn mineralization in the area are Banded Magnetite Quartzite (BMQ), unclassified calcareous silicates, and quartzite. We used ratio images derived from the scale and root mean squares (RMS) error imagesusing the multi-range spectral feature fitting (MRSFF) methodto delineate host rocks from the AVIRIS-NG image. The False Color Composites (FCCs) of different relative band depth images, derived from AVIRIS-NG spectral bands, were also used for delineating few minerals. These minerals areeither associated with the surface alteration resulting from the ore-bearing fluid migration orassociated with the redox-controlled supergene enrichments of the ore deposit.The results show that the AVIRIS-NG image products derived in this study can delineate surface signatures of mineralization in 1:10000 to 1:15000 scales to narrow down the targets for detailed exploration.This study alsoidentified the possible structural control over the knownsurface distribution of alteration and lithocap minerals of base metal mineralizationusing the ground-based residual magnetic anomaly map. This observationstrengthens the importance of the identified surface proxiesas an indicator of mineralization. X-ray fluorescence analysis of samples collectedfromselected locations within the study area confirms the Cu-Pb-Zn enrichment. The sulfide minerals were also identified in the microphotographs of polished sections of rock samples collected from the places where surface proxies of mineralization were observed in the field. This study justified the investigation to uti-lize surface signatures of mineralization identified using AVIRIS-NG dataand validated using field observations, geophysical, geochemical, and petrographical data

Itaconic acid and its applications for textile, pharma and agro-industrial purposes

Itaconic acid (IA) is a well-known bio-based monounsaturated organic acid (C5H6O4), with a white color and crystalline structure. It is widely used in the agro-based, plastics, textile, paint and pharmaceutical sectors, owing to its flexible structure, due to the presence of functional groups with covalent double bonds. IA is an alternative to the petrochemicals acrylic and methacrylic acids. Commercial manufacturing of IA using Aspergillus terreus is more economically effective and feasible, and the Department of Energy (DOE) of the United States added IA under the “top 12” organic chemicals in 2004. This review provides an overview on the synthesis of IA and improvement of its yield by mutagenesis and metabolic engineering of Aspergillus and other fungal strains, along with its wide applications for food, pharmaceutical and textile purposes

Molecular Insights into DNA Polymerase Deterrents for Ribonucleotide Insertion

DNA polymerases can misinsert ribonucleotides that lead to genomic instability. DNA polymerase β discourages ribonucleotide insertion with the backbone carbonyl of Tyr-271; alanine substitution of Tyr-271, but not Phe-272, resulted in a >10-fold loss in discrimination. The Y271A mutant also inserted ribonucleotides more efficiently than wild type on a variety of ribonucleoside (rNMP)-containing DNA substrates. Substituting Mn2+ for Mg2+ decreased sugar discrimination for both wild-type and mutant enzymes primarily by increasing the affinity for rCTP. This facilitated crystallization of ternary substrate complexes of both the wild-type and Y271A mutant enzymes. Crystallographic structures of Y271A- and wild type-substrate complexes indicated that rCTP is well accommodated in the active site but that O2′ of rCTP and the carbonyl oxygen of Tyr-271 or Ala-271 are unusually close (∼2.5 and 2.6 Å, respectively). Structure-based modeling indicates that the local energetic cost of positioning these closely spaced oxygens is ∼2.2 kcal/mol for the wild-type enzyme. Because the side chain of Tyr-271 also hydrogen bonds with the primer terminus, loss of this interaction affects its catalytic positioning. Our results support a model where DNA polymerase β utilizes two strategies, steric and geometric, with a single protein residue to deter ribonucleotide insertion

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit

Entry into mitosis is triggered by activation of Cdk1 and inactivation of its counteracting phosphatase PP2A/B55. Greatwall kinase inactivates PP2A/B55 via its substrates Ensa and ARPP19. Both Greatwall and Ensa/ARPP19 are regulated by phosphorylation, but the dynamic regulation of Greatwall activity and the phosphatases that control Greatwall kinase and its substrates are poorly understood. To address these questions we applied a combination of mathematical modelling and experiments using phospho-specific antibodies to monitor Greatwall, Ensa/ARPP19 and Cdk substrate phosphorylation during mitotic entry and exit. We demonstrate that PP2A/B55 is required for Gwl dephosphorylation at the essential Cdk site Thr194. Ensa/ARPP19 dephosphorylation is mediated by the RNA Polymerase II carboxy terminal domain phosphatase Fcp1. Surprisingly, neither Fcp1 nor PP2A appear to essential to dephosphorylate the bulk of mitotic Cdk1 substrates following Cdk1 inhibition. Taken together our results suggest a hierarchy of phosphatases coordinating Greatwall, Ensa/ARPP19 and Cdk substrate dephosphorylation during mitotic exit

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

BACKGROUND: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. RESULTS: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. CONCLUSION: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown