EXPLORATION OF PLANT BIOACTIVE FROM CASSIA FISTULA LEAVES FOR THE TREATMENT OF OVARIAN CANCER: AN INTEGRATIVE APPROACH

Objective: Paclitaxel is one of the most effective anticancer agents. It is used as a chemotherapy agent for a spectrum of cancer types. However,paclitaxel resistance is one of the foremost problems for chemotherapy. Most importantly, an emergence of paclitaxel resistance due to mutation(F270V) in β-tubulin has been extremely deliberated in recent years. With the rise of paclitaxel-resistant mutation in β-tubulin, there is a need to adda novel inhibitor from natural source, as they have less chance of getting resistance additionally less side effects. Keeping this in mind, we have utilizedexperimental and in silico approaches to isolate the potent inhibitor for β-tubulin target protein.Methods: We have extracted phytocompounds from Cassia fistula plant, and the structures were recognized with the help of gas chromatographymassspectrometry technique. Subsequently, oral bioavailability and toxicity analysis were executed for the extracted compounds by employingMOLINSPIRATION and OSIRIS program, respectively. Furthermore, docking analysis was performed using YASARA algorithm. In addition, bioactivityanalysis for the screened compounds was performed using prediction of activity spectra for substances program.Results: The results from our analysis clearly depict that HOP-22(29)-EN-3.BETA.-OL could be a promising inhibitor for the treatment of cancer andprovide direction for future research. Further in vitro and in vivo exploration is also required to identify whether HOP-22(29)-EN-3.BETA.-OL haveanticancer effect or not.Conclusion: The combination of computational approach and experimentalanalysis provides an easy approach to identify novel candidate for the target protein β-tubulin.Keywords: Phytochemicals, Gas chromatography mass spectrometry, Bioavailability, Molecular docking, Prediction of activity spectra for substancesprediction

STRUCTURAL AND FUNCTIONAL IMPACT OF G2032R MUTATION IN ROS1 – A THEORETICAL PERSPECTIVE

Objective: Drug resistance is an imperative issue in the treatment of patients with lung cancer. In this work, investigation of the drug resistance mechanism of G2032R mutation in ROS1 is carried out using computational simulation techniques.Methods: Molecular docking and molecular dynamics (MD) simulation approach have been utilized to uncover the mechanism behind crizotinib resistance in ROS1 at a molecular level. Normal mode analysis was carried out using ElNemo server which examines the movements and conformational changes in the protein structure. ArgusLab, PEARLS, and Autodock were employed for the docking analysis, whereas GROMACS package 4.5.3 was used for MD simulation approach.Results: The results from our analysis indicates that wild-type ROS1 (Protein Data Bank Code 3ZBF) could be more crucial for the crizotinib binding as it indicates largest binding affinity, minimum number of H-bonds, and higher flexibility than mutant-type ROS1. Moreover, the theoretical basis for the cause of drug insensitivity is the differences in the electrostatic properties of binding site residues between the wild and mutant ROS1 structures. Our analysis theoretically suggests that E-2027 is a key residue responsible for the ROS1 drug selectivity.Conclusion: Molecular docking and MD simulation results provide an explanation of the resistance caused by G2032R and may give a key clue for the drug design to encounter drug resistance.Â

What was the impact of a participatory research project in Australian Indigenous primary healthcare services? Applying a comprehensive framework for assessing translational health research to Lessons for the Best

Objectives To (1) apply the Framework to Assess the Impact from Translational health research (FAIT) to Lessons from the Best to Better the Rest (LFTB), (2) report on impacts from LFTB and (3) assess the feasibility and outcomes from a retrospective application of FAIT. Setting Three Indigenous primary healthcare (PHC) centres in the Northern Territory, Australia; project coordinating centre distributed between Townsville, Darwin and Cairns and the broader LFTB learning community across Australia. Participants LFTB research team and one representative from each PHC centre. Primary and secondary outcome measures Impact reported as (1) quantitative metrics within domains of benefit using a modified Payback Framework, (2) a cost-consequence analysis given a return on investment was not appropriate and (3) a narrative incorporating qualitative evidence of impact. Data were gathered through in-depth stakeholder interviews and a review of project documentation, outputs and relevant websites. Results LFTB contributed to knowledge advancement in Indigenous PHC service delivery; enhanced existing capacity of health centre staff, researchers and health service users; enhanced supportive networks for quality improvement; and used a strengths-based approach highly valued by health centres. LFTB also leveraged between $A1.4 and$A1.6 million for the subsequent Leveraging Effective Ambulatory Practice (LEAP) Project to apply LFTB learnings to resource development and creation of a learning community to empower striving PHC centres. Conclusion Retrospective application of FAIT to LFTB, although not ideal, was feasible. Prospective application would have allowed Indigenous community perspectives to be included. Greater appreciation of the full benefit of LFTB including a measure of return on investment will be possible when LEAP is complete. Future assessments of impact need to account for the limitations of fully capturing impact when intermediate/final impacts have not yet been realised and capture

In silico prediction of functional loss of cst3 gene in hereditary cerebral amyloid angiopathy

The computational identification of missense mutation in CST3 (CYSTATIN 3 or CYSTATIN C) gene has been done in the present study. The missense mutations in the CST3 gene will leads to hereditary cerebral amyloid angiopathy  The initiation of the analysis was done with SIFT followed by POLYPHEN-2 and I-Mutant 2.0 using 24 variants of CST3 gene of Homo sapiens which were derived from dbSNP. The analysis showed that 5 variants (Y60C, C123Y, L19P, Y88C, L94Q) were found to be less stable and damaging by SIFT, POLYPHEN-2 and I-MUTANT2.0. Furthermore the outputs of SNP & GO are collaborated with PHD-SNP (Predictor of Human Deleterious-Single Nucleotide Polymorphism) and PANTHER to predict 5 variants (Y60C, Y88C, C123Y, L19P, and L94Q) having clinical impact in causing the disease.  These findings will be certainly helpful for the present medical practitioners for the treatment of cerebral amyloid angiopathy

CareTrack Australia: assessing the appropriateness of adult healthcare: protocol for a retrospective medical record review

Introduction: In recent years in keeping with international best practice, clinical guidelines for common conditions have been developed, endorsed and disseminated by peak national and professional bodies. Yet evidence suggests that there remain considerable gaps between the care that is regarded as appropriate by such guidelines and the care received by patients. With an ageing population and increasing treatment options and expectations, healthcare is likely to become unaffordable unless more appropriate care is provided. This paper describes a study protocol that seeks to determine the percentage of healthcare encounters in which patients receive appropriate care for 22 common clinical conditions and the reasons why variations exist from the perspectives of both patients and providers. Methods/design: A random stratified sample of at least 1000 eligible participants will be recruited from a representative cross section of the adult Australian population. Participants' medical records from the years 2009 and 2010 will be audited to assess the appropriateness of the care received for 22 common clinical conditions by determining the percentage of healthcare encounters at which the care provided was concordant with a set of 522 indicators of care, developed for these conditions by a panel of 43 disease experts. The knowledge, attitudes and beliefs of participants and healthcare providers will be examined through interviews and questionnaires to understand the factors influencing variations in care.Tamara D Hunt, Shanthi A Ramanathan, Natalie A Hannaford, Peter D Hibbert, Jeffrey Braithwaite, Enrico Coiera, Richard O Day, Johanna I Westbrook, William B Runcima

Quality of Health Care for Children in Australia, 2012-2013.

Importance: The quality of routine care for children is rarely assessed, and then usually in single settings or for single clinical conditions. Objective: To estimate the quality of health care for children in Australia in inpatient and ambulatory health care settings. Design, Setting, and Participants: Multistage stratified sample with medical record review to assess adherence with quality indicators extracted from clinical practice guidelines for 17 common, high-burden clinical conditions (noncommunicable [n = 5], mental health [n = 4], acute infection [n = 7], and injury [n = 1]), such as asthma, attention-deficit/hyperactivity disorder, tonsillitis, and head injury. For these 17 conditions, 479 quality indicators were identified, with the number varying by condition, ranging from 9 for eczema to 54 for head injury. Four hundred medical records were targeted for sampling for each of 15 conditions while 267 records were targeted for anxiety and 133 for depression. Within each selected medical record, all visits for the 17 targeted conditions were identified, and separate quality assessments made for each. Care was evaluated for 6689 children 15 years of age and younger who had 15 240 visits to emergency departments, for inpatient admissions, or to pediatricians and general practitioners in selected urban and rural locations in 3 Australian states. These visits generated 160 202 quality indicator assessments. Exposures: Quality indicators were identified through a systematic search of local and international guidelines. Individual indicators were extracted from guidelines and assessed using a 2-stage Delphi process. Main Outcomes and Measures: Quality of care for each clinical condition and overall. Results: Of 6689 children with surveyed medical records, 53.6% were aged 0 to 4 years and 55.5% were male. Adherence to quality of care indicators was estimated at 59.8% (95% CI, 57.5%-62.0%; n = 160 202) across the 17 conditions, ranging from a high of 88.8% (95% CI, 83.0%-93.1%; n = 2638) for autism to a low of 43.5% (95% CI, 36.8%-50.4%; n = 2354) for tonsillitis. The mean adherence by condition category was estimated as 60.5% (95% CI, 57.2%-63.8%; n = 41 265) for noncommunicable conditions (range, 52.8%-75.8%); 82.4% (95% CI, 79.0%-85.5%; n = 14 622) for mental health conditions (range, 71.5%-88.8%); 56.3% (95% CI, 53.2%-59.4%; n = 94 037) for acute infections (range, 43.5%-69.8%); and 78.3% (95% CI, 75.1%-81.2%; n = 10 278) for injury. Conclusions and Relevance: Among a sample of children receiving care in Australia in 2012-2013, the overall prevalence of adherence to quality of care indicators for important conditions was not high. For many of these conditions, the quality of care may be inadequate

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

What was the impact of a participatory research project in Australian Indigenous primary healthcare services? Applying a comprehensive framework for assessing translational health research to Lessons for the Best

Objectives To (1) apply the Framework to Assess the Impact from Translational health research (FAIT) to Lessons from the Best to Better the Rest (LFTB), (2) report on impacts from LFTB and (3) assess the feasibility and outcomes from a retrospective application of FAIT.Setting Three Indigenous primary healthcare (PHC) centres in the Northern Territory, Australia; project coordinating centre distributed between Townsville, Darwin and Cairns and the broader LFTB learning community across Australia.Participants LFTB research team and one representative from each PHC centre.Primary and secondary outcome measures Impact reported as (1) quantitative metrics within domains of benefit using a modified Payback Framework, (2) a cost-consequence analysis given a return on investment was not appropriate and (3) a narrative incorporating qualitative evidence of impact. Data were gathered through in-depth stakeholder interviews and a review of project documentation, outputs and relevant websites.Results LFTB contributed to knowledge advancement in Indigenous PHC service delivery; enhanced existing capacity of health centre staff, researchers and health service users; enhanced supportive networks for quality improvement; and used a strengths-based approach highly valued by health centres. LFTB also leveraged between $A1.4 and$A1.6 million for the subsequent Leveraging Effective Ambulatory Practice (LEAP) Project to apply LFTB learnings to resource development and creation of a learning community to empower striving PHC centres.Conclusion Retrospective application of FAIT to LFTB, although not ideal, was feasible. Prospective application would have allowed Indigenous community perspectives to be included. Greater appreciation of the full benefit of LFTB including a measure of return on investment will be possible when LEAP is complete. Future assessments of impact need to account for the limitations of fully capturing impact when intermediate/final impacts have not yet been realised and captured