Protocol for The Toxin Study: Understanding clinical and patient reported response of children and young people with cerebral palsy to intramuscular lower limb Botulinum neurotoxin-A injections, exploring all domains of the ICF. A pragmatic longitudinal observational study using a prospective one-group repeated measures design

INTRODUCTION: Botulinum neurotoxin-A (BoNT-A) is an accepted treatment modality for the management of hypertonia in children and young people with cerebral palsy (CYPwCP). Nevertheless, there are concerns about the long-term effects of BoNT-A, with a lack of consensus regarding the most meaningful outcome measures to guide its use. Most evidence to date is based on short-term outcomes, related to changes at impairment level (restrictions of body functions and structures), rather than changes in adaptive skills (enabling both activity and participation). The proposed study aims to evaluate clinical and patient reported outcomes in ambulant CYPwCP receiving lower limb BoNT-A injections over a 12-month period within all domains of the WHO's International Classification of Functioning, Disability and Health and health-related quality of life (HRQoL). METHODS AND ANALYSIS: This pragmatic prospective longitudinal observational study will use a one-group repeated measures design. Sixty CYPwCP, classified as Gross Motor Function Classification System (GMFCS) levels I-III, aged between 4 and 18 years, will be recruited from an established movement disorder service in London, UK. Standardised clinical and patient reported outcome measures within all ICF domains; body structures and function, activity (including quality of movement), goal attainment, participation and HRQoL, will be collected preinjection and at 6 weeks, 6 months and up to 12 months postinjection. A representative subgroup of children and carers will participate in a qualitative component of the study, exploring how their experience of BoNT-A treatment relates to clinical outcome measures. ETHICS AND DISSEMINATION: Central London Research Ethics Committee has granted ethics approval (#IRAS 211617 #REC 17/LO/0579). Findings will be disseminated in peer-reviewed publications, conferences and via networks to participants and relevant stakeholders using a variety of accessible formats including social media

Protocol for The Toxin Study: Understanding clinical and patient reported response of children and young people with cerebral palsy to intramuscular lower limb Botulinum neurotoxin-A injections, exploring all domains of the ICF. A pragmatic longitudinal observational study using a prospective one-group repeated measures design

This is the final version. Available from BMJ Publishing Group via the DOI in this record. Introduction: Botulinum neurotoxin-A (BoNT-A) is an accepted treatment modality for the management of hypertonia in children and young people with cerebral palsy (CYPwCP). Nevertheless, there are concerns about the long-term effects of BoNT-A, with a lack of consensus regarding the most meaningful outcome measures to guide its use. Most evidence to date is based on short-term outcomes, related to changes at impairment level (restrictions of body functions and structures), rather than changes in adaptive skills (enabling both activity and participation). The proposed study aims to evaluate clinical and patient reported outcomes in ambulant CYPwCP receiving lower limb BoNT-A injections over a 12-month period within all domains of the WHO’s International Classification of Functioning, Disability and Health and health-related quality of life (HRQoL). Methods and analysis: This pragmatic prospective longitudinal observational study will use a one-group repeated measures design. Sixty CYPwCP, classified as Gross Motor Function Classification System (GMFCS) levels I–III, aged between 4 and 18 years, will be recruited from an established movement disorder service in London, UK. Standardised clinical and patient reported outcome measures within all ICF domains; body structures and function, activity (including quality of movement), goal attainment, participation and HRQoL, will be collected preinjection and at 6 weeks, 6 months and up to 12 months postinjection. A representative subgroup of children and carers will participate in a qualitative component of the study, exploring how their experience of BoNT-A treatment relates to clinical outcome measures. Ethics and dissemination: Central London Research Ethics Committee has granted ethics approval (#IRAS 211617 #REC 17/LO/0579). Findings will be disseminated in peer-reviewed publications, conferences and via networks to participants and relevant stakeholders using a variety of accessible formats including social media.National Institute for Health Research (NIHR

Long-term cultivation of colorectal carcinoma cells with anti-cancer drugs induces drug resistance and telomere elongation: an in vitro study

BACKGROUND: The role of telomerase activation in the expression and/or maintenance of drug resistance is not clearly understood. Therefore, we investigated the relationships, among the telomerase activity, telomere length and the expression of multidrug resistance genes in colorectal cancer cell lines cultivated with anti-cancer drugs. METHODS: LoVo and DLD-1 cells were continuously grown in the presence of both CDDP and 5-FU for up to 100 days. Cell proliferation, telomerase activity, telomere length and the expression of multidrug resistance genes were serially monitored as the PDL increased. RESULTS: The expression of multidrug resistance genes tended to increase as the PDL increased. However, an abnormal aneuploid clone was not detected as far as the cells were monitored by a DNA histogram analysis. Tumor cells showing resistance to anti-cancer drugs revealed a higher cell proliferation rate. The telomere length gradually increased with a progressive PDL. The telomerase activity reached a maximum level at 15 PDL in LoVo cells and at 27 PDL in DLD-1 cells. An increase in the mRNA expression of the telomerase components, especially in hTERT and in hTR, was observed at the same PDLs. CONCLUSIONS: These results suggest that a high telomerase activity and an elongation of telomeres both appear to help maintain and/or increase drug resistance in colorectal cancer cells. Cancer cells with long telomeres and a high proliferative activity may thus be able to better survive exposure to anti-cancer drugs. This is presumably due to an increased chromosome stability and a strong expression of both mdr-1 and MRP genes

Attracting and retaining health workers in rural areas: investigating nurses’ views on rural posts and policy interventions

<p>Abstract</p> <p>Background</p> <p>Kenya has bold plans for scaling up priority interventions nationwide, but faces major human resource challenges, with a lack of skilled workers especially in the most disadvantaged rural areas.</p> <p>Methods</p> <p>We investigated reasons for poor recruitment and retention in rural areas and potential policy interventions through quantitative and qualitative data collection with nursing trainees. We interviewed 345 trainees from four purposively selected Medical Training Colleges (MTCs) (166 pre-service and 179 upgrading trainees with prior work experience). Each interviewee completed a self-administered questionnaire including likert scale responses to statements about rural areas and interventions, and focus group discussions (FGDs) were conducted at each MTC.</p> <p>Results</p> <p>Likert scale responses indicated mixed perceptions of both living and working in rural areas, with a range of positive, negative and indifferent views expressed on average across different statements. The analysis showed that attitudes to working in rural areas were significantly positively affected by being older, but negatively affected by being an upgrading student. Attitudes to living in rural areas were significantly positively affected by being a student at the MTC furthest from Nairobi.</p> <p>During FGDs trainees raised both positive and negative aspects of rural life. Positive aspects included lower costs of living and more autonomy at work. Negative issues included poor infrastructure, inadequate education facilities and opportunities, higher workloads, and inadequate supplies and supervision. Particular concern was expressed about working in communities dominated by other tribes, reflecting Kenya’s recent election-related violence.</p> <p>Quantitative and qualitative data indicated that students believed several strategies could improve rural recruitment and retention, with particular emphasis on substantial rural allowances and the ability to choose their rural location. Other interventions highlighted included provision of decent housing, and more rapid career advancement. However, recently introduced short term contracts in named locations were not favoured due to their lack of pension plans and job security.</p> <p>Conclusions</p> <p>This study identified a range of potential interventions to increase rural recruitment and retention, with those most favored by nursing students being additional rural allowances, and allowing choice of rural location. Greater investment is needed in information systems to evaluate the impact of such policies.</p

Fish Intelligence, Sentience and Ethics

Fish are one of the most highly utilised vertebrate taxa by humans; they are harvested from wild stocks as part of global fishing industries, grown under intensive aquaculture conditions, are the most common pet and are widely used for scientific research. But fish are seldom afforded the same level of compassion or welfare as warm-blooded vertebrates. Part of the problem is the large gap between people’s perception of fish intelligence and the scientific reality. This is an important issue because public perception guides government policy. The perception of an animal’s intelligence often drives our decision whether or not to include them in our moral circle. From a welfare perspective, most researchers would suggest that if an animal is sentient, then it can most likely suffer and should therefore be offered some form of formal protection. There has been a debate about fish welfare for decades which centres on the question of whether they are sentient or conscious. The implications for affording the same level of protection to fish as other vertebrates are great, not least because of fishing-related industries. Here, I review the current state of knowledge of fish cognition starting with their sensory perception and moving on to cognition. The review reveals that fish perception and cognitive abilities often match or exceed other vertebrates. A review of the evidence for pain perception strongly suggests that fish experience pain in a manner similar to the rest of the vertebrates. Although scientists cannot provide a definitive answer on the level of consciousness for any nonhuman vertebrate, the extensive evidence of fish behavioural and cognitive sophistication and pain perception suggests that best practice would be to lend fish the same level of protection as any other vertebrate

The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops

The topic of this book is dedicated to the analysis, fate, metabolism, effects, and remediation of pharmaceutically active compounds in water-soil-biota systems. While the majority of readers are likely to already have a broad understanding of potential entry points, flows, transformation pathways, and temporary and permanent sinks of drugs in the environment, the objectives of this first chapter are fourfold: (a) to provide a concise overview of the journey a drug takes from its inception at the laboratory bench to the desk of the reviewer at the regulatory agency; (b) to understand the biological and physiological processes a drug undergoes from administration to humans – or to the animal in case of veterinary medicines – to their excretion and ultimately discharge into wastes; (c) to describe the physico-chemical space small-molecule drugs reside in as this characteristic largely governs their later environmental fate; (d) to review their presence, fate, and metabolism in crops and plants determined using innovative analytical methods; as well as (e) to evaluate the effects and remediation of drugs in crops and biota.Peer reviewe