Analytical Purity Determinations of Universal Food-Spice Curcuma longa through a QbD Validated HPLC Approach with Critical Parametric Predictors and Operable-Design's Monte Carlo Simulations: Analysis of Extracts, Forced-Degradants, and Capsules and Tablets-Based Pharmaceutical Dosage Forms.

Applications of analytical quality by design (QbD) approach for developing HPLC (High Performance Liquid Chromatography) methods for food components assays, and separations of complex natural product mixtures, are still limited. The current study developed and validated, for the first time, a stability-indicating HPLC method for simultaneous determinations of curcuminoids in Curcuma longa extracts, tablets, capsules, and curcuminoids' forced degradants under different experimental conditions. Towards separation strategy, critical method parameters (CMPs) were defined as the mobile phase solvents' percent-ratio, the pH of the mobile phase, and the stationary-phase column temperature, while the peaks resolution, retention time, and the number of theoretical plates were recognized as the critical method attributes (CMAs). Factorial experimental designs were used for method development, validation, and robustness evaluation of the procedure. The Monte Carlo simulation evaluated the developing method's operability, and that ensured the concurrent detections of curcuminoids in natural extracts, commercial-grade pharmaceutical dosage-forms, and the forced degradants of the curcuminoids in a single mixture. The optimum separations were accomplished using the mobile phase, consisting of an acetonitrile-phosphate buffer (54:46 v/v, 0.1 mM) with 1.0 mL/min flow rate, 33 °C column temperature, and 385 nm wavelength for UV (Ultra Violet) spectral detections. The method is specific, linear (R2 ≥ 0.999), precise (% RSD < 1.67%), and accurate (% recovery 98.76-99.89%), with LOD (Limit of Detection) and LOQ (Limit of Quantitation) at 0.024 and 0.075 µg/mL for the curcumin, 0.0105 µg/mL and 0.319 µg/mL for demethoxycurcumin, and 0.335 µg/mL and 1.015 µg/mL for the bisdemethoxycurcumin, respectively. The method is compatible, robust, precise, reproducible, and accurately quantifies the composition of the analyte mixture. It exemplifies the use of the QbD approach in acquiring design details for developing an improved analytical detection and quantification method.

Environmental sustainability assessment of softwood and hardwood seedlings production in forest nurseries: A case study from Pakistan.

This article describes the environmental impacts of producing a single seedling in forest nurseries of selected districts (i.e., Haripur, Abbottabad, and Mansehra) of Hazara Division of Khyber Pakhtunkhwa, Pakistan using the life cycle assessment (LCA) approach. This study was based on the cradle-to-gate approach which begins with the pre-nursery stage and progresses toward the main nursery before transplanting seedlings into the plantation site. Data or life cycle inventory (LCI) of seedling production were collected through questionnaire surveys and personal meetings with forest nurseries managers and workers regarding consumption of different inputs such as electricity, diesel, fertilizers, herbicides, and polyethylene bags, organic manure, and water consumption. The SimaPro software version 8.5 and the CML2000 v2.05 environmental model was applied to perform life cycle impact assessment (LCIA) for a single seedling production in forest nurseries in the study area. In line with the objectives of the study, primary data regarding inputs and outputs of the nurseries were collected from 35 nurseries in the study area by using a random questionnaire method. In addition, secondary data were taken from online databases such as Eco-invent v.3.2 CORRIM and peer-reviewed published literature. For this study, a functional unit of a single seedling was considered. Production weighted average data were modeled in the latest environmental modeling software i.e., SimaPro v.8.5 for ten US-EPA most wanted environmental impacts, such as global warming potential (GWP), abiotic depletion (AD), eutrophication potential (EP), acidification potential (AP), freshwater aquatic eco-toxicity (FAE), marine water eco-toxicity (MWE), terrestrial eco-toxicity (TE), ozone layer depletion (OLD), photochemical oxidation (PO), and human toxicity (HT). The results showed that the highest environmental impact posed by a single seedling was marine aquatic eco-toxicity (11.31360 kg 1,4-DB eq), followed by global warming potential (0.02945 kg CO2 eq) and (0.01227 kg 1,4-DB eq) human toxicity. The primary reason for these environmental burdens was the use of synthetic fertilizers in forest nurseries and the consumption of fossil fuels in nursery mechanization and transportation activities. The total cumulative energy demand for a single seedling was (0.800 MJ) with more than 90% contribution from fossil fuel energy resources such as petrol and diesel. It is therefore highly recommended to use renewable energy resources and organic fertilizers instead of chemical fertilizers in forest nurseries to avoid and minimize greenhouse gas emissions (GHS) and other toxic emissions in the study area.

A systematic review and meta-analysis of antibiotic prophylaxis in skin graft surgery: A protocol.

INTRODUCTION: There is little evidence-based guidance on the use of prophylactic antibiotics in skin surgery; whilst antibiotics may protect against surgical site infections (SSI), they have associated side effects, increase the risk of adverse events, and can propagate antibiotic resistance. We present a protocol for a systematic review to establish whether the benefit of prophylactic antibiotics overrides the risk, for patients undergoing autograft surgery. METHODS: The systematic review will be registered a priori on researchregistry.com and will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A search strategy will be devised to investigate 'skin graft surgery and use of antibiotics'. The following electronic databases will be searched, 1979-2018: PubMed, MEDLINE®, EMBASE, SCOPUS, CINAHL, PsychINFO, SciELO, The Cochrane Library, including the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature will be searched. All comparative study designs reporting on the use of antibiotics in skin graft surgery will be considered for inclusion, namely randomized controlled trials (RCTs). Two trained independent teams will screen all titles and abstracts, followed by relevant full texts, for eligibility. Data will be extracted under standardized extraction fields into a preformatted database. Note will be made of the indication for skin graft surgery (traumatic, congenital, malignant, benign), the graft site (head & neck, trunk, upper extremities, lower extremities), type of skin graft (split thickness, full-thickness). The primary outcome will be occurrence of SSI at the donor and/or recipient sites. Secondary outcomes, if reported, will include: length of hospital stay, revision surgery required, cost of medical care, time to wound healing and cosmetic outcome. ETHICS AND DISSEMINATION: The systematic review will be published in a peer-reviewed journal and presented at national and international meetings within fields of plastic, reconstructive, and aesthetic surgery. The work will be disseminated electronically and in print. Brief reports of the review and findings will be disseminated to interested parties through email and direct communication. The review aims to guide healthcare practice and policy.

Use of autologous fat grafting in reconstruction following mastectomy and breast conserving surgery: An updated systematic review protocol.

INTRODUCTION: Use of autologous fat grafting (AFG) for breast reconstructive surgery is gaining acceptance, but concerns regarding its efficacy and safety remain. We present a protocol for a systematic review that aims to update the findings since our previous systematic review on a number of outcomes of AFG. METHODS: The systematic review has been registered a priori (UIN: reviewregistry308). All study designs, including randomised controlled trials, cohort studies, case-controlled studies and case reports/series, reporting original data, on women undergoing AFG for breast reconstruction following mastectomy or breast conserving surgery, will be included. Six categorical outcomes will be assessed: oncological; clinical; aesthetic/functional; patient-reported; process; and radiological.The search strategy will be devised to investigate 'fat grafting and breast reconstruction'. Electronic databases will be searched, 01 April 2014 to 21 August 2017: PubMed, MEDLINE®, EMBASE, SCOPUS, CINAHL, PsychINFO, SciELO, The Cochrane Library, including the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature will be searched. Two trained, independent teams will screen all titles and abstracts, and relevant full texts, for eligibility. Data will be extracted under standardised extraction fields into a preformatted database. ETHICS AND DISSEMINATION: The systematic review will be published in a peer-reviewed journal and presented at national and international meetings within fields of plastic, reconstructive and aesthetic surgery, and surgical oncology. The work will be disseminated electronically and in print. Brief reports of the review and findings will be disseminated to interested parties through email and direct communication. The review aims to guide healthcare practice and policy.

An assessment of the compliance of systematic review articles published in craniofacial surgery with the PRISMA statement guidelines: A systematic review.

CONTEXT: Systematic review evidence is increasing within craniofacial surgery. Compliance with recognised reporting guidelines for systematic review evidence has not been assessed. OBJECTIVE: To assess the compliance of systematic reviews published in craniofacial journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting criteria. DATA SOURCES, SEARCH TERMS AND STUDY SELECTION: Thomson Reuters impact factor was used to identify three top craniofacial journals. A search for all systematic review articles published in these journals from 1st May 2010 to 30th April 2015 was conducted using MEDLINE PubMed. DATA EXTRACTION: Two independent researchers assessed each study for inclusion and performed the data extraction. Data included the article reference information; the pathology and interventions examined and compliance of each review article with the PRISMA checklist. DATA SYNTHESIS AND RESULTS: 97 studies were returned by the search. 62 studies proceeded to data extraction. The mean percentage of applicable PRISMA items that were met across all studies was 72.5% (range 28.6-96.2%). The area of poorest compliance was with the declaration of a study protocol (19.4% of studies). Only 37.1% of studies declared their source of funding. CONCLUSIONS: Compliance of systematic review articles within craniofacial surgery with areas of the PRISMA checklist could be improved.

Use of autologous fat grafting for reconstruction postmastectomy and breast conserving surgery: a systematic review protocol.

INTRODUCTION: There is growing interest in the potential use of autologous fat grafting (AFG) for the purposes of breast reconstruction. However, concerns have been raised regarding the technique's clinical effectiveness, safety and interference with screening mammography. The objective of this systematic review was to determine the oncological, clinical, aesthetic and functional, patient reported, process and radiological outcomes for AFG. METHODS AND ANALYSIS: All original studies, including randomised controlled trials, cohorts studies, case-control studies, case series and case reports involving women undergoing breast reconstruction. All AFG techniques performed for the purposes of reconstruction in the postmastectomy or breast conserving surgery setting will be considered. Outcomes are defined within this protocol along; oncological, clinical, aesthetic and functional, patient reported, process and radiological domains. The search strategy has been devised to find papers about 'fat grafting and breast reconstruction' and is outlined within the body of this protocol. The full search strategy is outlined within the body of the protocol. The following electronic databases will be searched from 1 January 1986 to 6 June 2013: PubMed, MEDLINE, EMBASE, SCOPUS, CINAHL, PsycINFO, SciELO, The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature searches will also be conducted as detailed in our review protocol. Eligibility assessment occurred in two stages, title and abstract screening and then full text assessment. Data were extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. It will also be presented at national and international conferences in the fields of plastic, reconstructive and aesthetic surgery and at more general surgical and methodological conferences. It will be disseminated electronically and in print. Brief reports of the review findings will be disseminated directly to the appropriate audiences of surgeons and societies through email and other modes of communication. Updates of the review will be conducted to inform and guide healthcare practice and policy. PROTOCOL REGISTRATION: PROSPERO-National Institute of Health Research (NIHR) Prospective Register of Systematic Reviews (CRD42013005254).

Handover in Trauma and Orthopaedic Surgery - A Human Factors Assessment.

UNLABELLED: Handovers permeate healthcare delivery systems. They are critical for patient safety and continuity of care, but also for logistics and clinical efficiency. Poor handovers can cause reduced efficiency, delayed discharge or time to operation, and contributes to patient harm. The Objective was to conduct a human factors assessment (HFA) using a systems approach to study the handover process at an Orthopaedic unit, determine barriers to information transfer, and suggest improvements. A direct observation model was used to help provide insights on the evening handover process. A Systems Engineering Initiative for Patient Safety (SEIPS) model was used to provide a framework. A total of ten handover sessions were observed and the junior doctors were interviewed using a semi-structured approach. Participants had two chief centres of complaint: workspace and environmental issues (such as a small, hot, uncomfortable room), and the lack of the junior house officer at handover leading to 'signal loss' with respect to sick patients who may not be handed over fully. The process also lacked standardisation and structure compounding the potential loss of information. CONCLUSION: Good handover remains a cornerstone of safe and effective clinical practice and continuity of care. This study has shown how an HFA can be useful in determining problems with the handover process locally. It suggests an approach for improvement and recommends better training at all levels in this aspect of patient care.

Altered gene expressions involved in energy expenditure in 5-HT(2C) receptor mutant mice.

Mice with a targeted null mutation of the serotonin 5-HT(2C) receptor gene exhibit hyperphagia that leads to a late-onset obesity. Here we show that oxygen consumption was decreased in fed and fasted obese mutants. No phenotypic differences were observed in uncoupling protein-1 (UCP-1) mRNA levels in brown adipose tissues and UCP-3 mRNA in skeletal muscle. UCP-2 mRNA levels were significantly increased in white adipose tissue (4-fold) and skeletal muscle (47%) in older obese mutant mice, whereas UCP-2 mRNA in liver are significantly increased in both young lean (54% increase) and older obese (52% increase) mutant mice. In contrast, 5-HT(2C) receptor mutants displayed age-dependent decreases in beta 3-adrenergic receptor (beta 3-AR) mRNA levels in white adipose tissue, however, no such changes were observed in brown adipose tissue. These results indicate that a mutation of 5-HT(2C) receptor gene leads to a secondary decrease in beta 3-AR gene expression that is related to enhanced adiposity.

Patient attitudes to over-the-counter drugs and possible professional responses to self-medication.

BACKGROUND: There is a paucity of research about patients' attitudes towards their doctor's recommending over-the-counter (OTC) remedies or about how patients respond to the doctor's suggestion to try an OTC remedy. OBJECTIVES: The aim of this study was to ascertain the attitudes of patients to OTC drugs. METHODS: 505 consecutive patients from each of six participating practices filled in a questionnaire. RESULTS: A total of 2765 (91.3%) patients responded. The responses from 2624 patients were from adults and are presented here. Based on the number of valid responses to each question, 53.8% of these patients were exempt from prescription charges, 55.1% took regular prescribed medication and 24.6% stated that they used OTC remedies regularly. There were generally positive attitudes to doctors enquiring about prior OTC use as well as to doctors making OTC recommendations in the consultation. However, patients expressed fairly negative attitudes towards pharmacists making generic substitutions and were even more hostile to the idea that pharmacists should make therapeutic substitutions. CONCLUSION: In conclusion, GPs should consider asking their patients regularly about their use of OTC medicines and also consider recommending OTC use if this is cheaper than FP10s. However, the public at present do not appear to be prepared for interventions by the pharmacist.