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1.
Br J Biomed Sci ; 81: 12148, 2024.
Article in English | MEDLINE | ID: mdl-38501148

ABSTRACT

Introduction: Active learning is a useful tool to enhance student engagement and support learning in diverse educational situations. We aimed to assess the efficacy of an active learning approach within a large interprofessional first year Medical Cell Biology module taken by six healthcare programmes across the School of Biomedical Sciences at Ulster University, United Kingdom. Materials and methods: An active learning approach was developed for weekly formative assessment using Smartwork to design a weekly interactive multiple-choice quiz to reinforce key concepts specifically for each lecture. We tracked and assessed student performance in the module overall and in each element of course work and exam for 2 years prior to and following the introduction of an active learning strategy to engage and support learning for students from all academic backgrounds and abilities. Results: Full engagement with active learning was significantly associated with an increased overall module performance as well as a significantly increased performance in each element of class test (No engagement vs. Full engagement, p < 0.001), exam (No Engagement vs. Full engagement, p < 0.05) and coursework (No engagement vs. Full engagement, p < 0.001) within this overall total (No Engagement vs. Full engagement, p < 0.01). Partial engagement with active learning was associated significantly improved class test (No engagement vs. partially engaged, p < 0.001) and coursework (No engagement vs. partially engaged, p < 0.05) performance. While a trend toward increased performance in exam and overall module mark was observed, these were not significant. Discussion: Active learning is a useful tool to support student learning across a range of healthcare programmes taken by students with differing backgrounds and academic abilities in an interprofessional and widening participation setting. Student engagement in active learning was highlighted as a key contributory factor to enhanced student performance in all aspects of assessment.


Subject(s)
Problem-Based Learning , Students , Humans , United Kingdom
2.
Eur J Pharmacol ; 954: 175855, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37391009

ABSTRACT

Clinical approval of the glucagon-like peptide-1 (GLP-1) mimetic exenatide for the treatment of type 2 diabetes highlights the therapeutic effectiveness of venom-derived peptides. In the present study, we examined and characterised the glucose-lowering potential of synthetic Jingzhaotoxin IX and Jingzhaotoxin XI peptides, which were originally isolated from the venom of the Chinese earth tarantula Chilobrachys jingzhao. Following confirmation of lack of beta-cell toxicity of synthetic peptides, assessment of enzymatic stability and effects on in vitro beta-cell function were studied, alongside putative mechanisms. Glucose homeostatic and appetite suppressive actions of Jingzhaotoxin IX and Jingzhaotoxin XI alone, or in combination with exenatide, were then assessed in normal overnight fasted C57BL/6 mice. Synthetic Jingzhaotoxin peptides were non-toxic and exhibited a decrease in mass of 6 Da in Krebs-Ringer bicarbonate buffer suggesting inhibitor cysteine knot (ICK)-like formation, but interestingly were liable to plasma enzyme degradation. The Jingzhaotoxin peptides evoked prominent insulin secretion from BRIN BD11 beta-cells, with activity somewhat characteristic of Kv2.1 channel binding. In addition, Jingzhaotoxin peptides enhanced beta-cell proliferation and provided significant protection against cytokine-induced apoptosis. When injected co-jointly with glucose, the Jingzhaotoxin peptides slightly decreased blood-glucose levels but had no effect on appetite in overnight fasted mice. Whilst the Jingzhaotoxin peptides did not enhance exenatide-induced benefits on glucose homeostasis, they augmented exenatide-mediated suppression of appetite. Taken together, these data highlight the therapeutic potential of tarantula venom-derived peptides, such as Jingzhaotoxin IX and Jingzhaotoxin XI either alone or in combination with exenatide, for diabetes and related obesity.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Spider Venoms , Spiders , Mice , Animals , Exenatide/pharmacology , Exenatide/therapeutic use , Diabetes Mellitus, Type 2/metabolism , Spider Venoms/pharmacology , Insulin-Secreting Cells/metabolism , Mice, Inbred C57BL , Peptides/pharmacology , Peptides/therapeutic use , Peptides/metabolism , Glucose/metabolism , Spiders/metabolism , Insulin/metabolism , Hypoglycemic Agents
3.
Biochem Pharmacol ; 212: 115544, 2023 06.
Article in English | MEDLINE | ID: mdl-37044298

ABSTRACT

Proof-of-concept for therapeutic application of venom-derived compounds in diabetes is exemplified by the incretin mimetic, exenatide, originally extracted from the saliva of the venomous Heloderma suspectum lizard. In this regard, we have isolated and sequenced a novel 28 amino acid peptide named Δ-theraphotoxin-Ac1 (Δ-TRTX-AC1) from venom of the Mexican Blond tarantula spider Aphonopelma chalcodes, with potential therapeutic benefits for diabetes. Following confirmation of the structure and safety profile of the synthetic peptide, assessment of enzymatic stability and effects of Δ-TRTX-AC1 on in vitro beta-cell function were studied, alongside potential mechanisms. Glucose homeostatic and satiety actions of Δ-TRTX-AC1 alone, and in combination with exenatide, were then assessed in C57BL/6 mice. Synthetic Δ-TRTX-AC1 was shown to adopt a characteristic inhibitor cysteine knot (ICK)-like structure and was non-toxic to beta-cells. Δ-TRTX-AC1 evoked glucose-dependent insulin secretion from BRIN BD11 cells with bioactivity confirmed in murine islets. Insulin secretory potency was established to be dependent on KATP and Ca2+ channel beta-cell signalling. In addition, Δ-TRTX-AC1 enhanced beta-cell proliferation and provided significant protection against cytokine-induced apoptosis. When injected co-jointly with glucose in mice at a dose of 250 nmol/kg, Δ-TRTX-AC1 decreased blood-glucose levels and evoked a significant satiating effect. Moreover, whilst Δ-TRTX-AC1 did not enhance exenatide induced benefits on glucose homeostasis, the peptide significantly augmented exenatide mediated suppression of appetite. Together these data highlight the therapeutic potential of tarantula spider venom-derived peptides, such as Δ-TRTX-Ac1, for diabetes and related obesity.


Subject(s)
Insulin-Secreting Cells , Spider Venoms , Mice , Animals , Exenatide/pharmacology , Spider Venoms/metabolism , Appetite , Mice, Inbred C57BL , Peptides/metabolism , Glucose/metabolism , Insulin/metabolism
4.
BMC Emerg Med ; 22(1): 95, 2022 06 03.
Article in English | MEDLINE | ID: mdl-35659572

ABSTRACT

BACKGROUND: There are potential health gains such as reducing early deaths, years spent in ill-health and costs to society and the health and care system by encouraging NHS staff to use encounters with patients to help individuals significantly reduce their risk of disease. Emergency department staff and paramedics are in a unique position to engage with a wide range of the population and to use these contacts as opportunities to help people improve their health. The aim of this research was to examine barriers and facilitators to effective health promotion by urgent and emergency care staff. METHODS: A systematic search of the literature was performed to review and synthesise published evidence relating to barriers and facilitators to effective health promotion by urgent and emergency care staff. Medical and social science databases were searched for articles published between January 2000 and December 2021 and the reference lists of included articles were hand searched. Two reviewers independently screened the studies and assessed risk of bias. Data was extracted using a bespoke form created for the study. RESULTS: A total of 19 papers were included in the study. Four themes capture the narratives of the included research papers: 1) should it be part of our job?; 2) staff comfort in broaching the topic; 3) format of health education; 4) competency and training needs. Whilst urgent and emergency care staff view health promotion as part of their job, time restraints and a lack of knowledge and experience are identified as barriers to undertaking health promotion interventions. Staff and patients have different priorities in terms of the health topics they feel should be addressed. Patients reported receiving books and leaflets as well as speaking with a knowledgeable person as their preferred health promotion approach. Staff often stated the need for more training. CONCLUSIONS: Few studies have investigated the barriers to health promotion interventions in urgent and emergency care settings and there is a lack of evidence about the acceptability of health promotion activity. Additional research is needed to determine whether extending the role of paramedics and emergency nurses to include health promotion interventions will be acceptable to staff and patients.


Subject(s)
Emergency Medical Services , Allied Health Personnel , Health Promotion , Humans
5.
Perspect Public Health ; 142(3): 135-136, 2022 05.
Article in English | MEDLINE | ID: mdl-34674589
6.
J Laryngol Otol ; 135(7): 599-601, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34016194

ABSTRACT

OBJECTIVE: British Thyroid Association 2014 guidelines emphasised ultrasound assessment of nodules. One ultrasonographic differentiator of debatable relevance is intra-nodular vascularity. This is the first UK study conducted to address this question. METHODS: Ultrasound reports for thyroid surgery patients over 10 years were retrospectively reviewed. Reports documenting 'intra-nodular vascularity or flow' were analysed. Reports identifying peripheral vascularity only or no intra-nodular flow formed the control group. Concordance with final histology was used to determine the odds ratio for malignancy. RESULTS: A total of 306 patients were included, and 119 (38.9 per cent) nodules demonstrated intra-nodular vascularity. Of these, 60 (50.4 per cent) were malignant compared with 42 per cent in the control group. Intra-nodular vascularity was not a statistically significant predictor of malignancy with an odds ratio of 1.39 (p = 0.18, 95 per cent confidence interval, 0.86-2.23). CONCLUSION: Intra-nodular vascularity in isolation was not a reliable predictor of malignancy. This supports other world literature studies. Although intra-nodular flow should not be relied upon in isolation, interpretation in conjunction with other suspicious findings enhances the predictive value.


Subject(s)
Thyroid Neoplasms/diagnostic imaging , Thyroid Nodule/diagnostic imaging , Ultrasonography , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Tertiary Care Centers , Thyroid Neoplasms/blood supply , Thyroid Neoplasms/pathology , Thyroid Nodule/blood supply , Thyroid Nodule/pathology , United Kingdom
7.
Mol Cell Endocrinol ; 496: 110523, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31352038

ABSTRACT

Xenin-25 undergoes rapid enzyme metabolism following secretion. Early studies demonstrated bioactivity of a C-terminal hexapeptide fragment of xenin-25, namely xenin-6, which were enhanced through introduction of a reduced N-terminal peptide bond, to yield Ψ-xenin-6. The present study was undertaken to define the biological actions and potential antidiabetic properties of Ψ-xenin-6. In vitro enzymatic stability, insulin and glucagon secretory activity, as well as effects on beta-cell survival were determined. Studies in mice were used to assess the impact of Ψ-xenin-6 on glucose homeostasis and satiety. Ψ-xenin-6 was resistant to murine plasma degradation. In BRIN-BD11 cells and isolated murine islets, Ψ-xenin-6 significantly stimulated insulin secretion, and prominently enhanced the insulinotropic actions of GIP. Xenin-6 and Ψ-xenin-6 had no impact on glucagon secretion, although xenin-6 partially reversed the glucagonotropic action of GIP. Further in vitro investigations revealed that, similar to GLP-1, Ψ-xenin-6 significantly augmented proliferation of human and rodent clonal beta-cells, whilst also fully protecting against cytokine-induced beta-cell cytotoxicity, with greater potency than xenin-25 and xenin-6. When administered to mice in combination with glucose, Ψ-xenin-6 significantly reduced glucose levels and enhanced glucose-induced insulin release, with a duration of biological action beyond 8 h. Ψ-xenin-6 also significantly enhanced the glucose-lowering action of GIP in vivo. In overnight fasted mice, Ψ-xenin-6 exhibited satiety actions at both 25 and 250 nmol/kg. These data demonstrates that Ψ-xenin-6 is a metabolically stable C-terminal fragment analogue of xenin-25, with a metabolic action profile that merits further study as a potential antidiabetic compound.


Subject(s)
Glucagon/metabolism , Hypoglycemic Agents , Insulin Secretion/drug effects , Insulin-Secreting Cells/metabolism , Neurotensin , Animals , Cell Line , Glucose/pharmacology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Mice , Neurotensin/chemistry , Neurotensin/pharmacology
8.
Biochem Pharmacol ; 155: 264-274, 2018 09.
Article in English | MEDLINE | ID: mdl-30028989

ABSTRACT

Glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that exert an array of beneficial actions on metabolism and cognitive function. GLP-1-based therapeutics have been highly successful in terms of obesity and diabetes management, however GIP therapies have found no clinical utility to date. In the present study we describe, for the first time, the therapeutic effectiveness of a novel GIP/GLP-1 hybrid peptide based on the amino acid sequences of GIP, GLP-1 and the clinically approved GLP-1 mimetic, exendin-4. The hybrid peptide, N-ac(d-Ala2)GIP/GLP-1-exe, was enzymatically stable for up to 12 h when incubated with DPP-4. N-ac(d-Ala2)GIP/GLP-1-exe significantly (P < 0.001) stimulated insulin secretion from BRIN-BD11 cells and isolated mouse islets, and evoked dose-dependent increases (P < 0.001) in cAMP production in both GIP-R and GLP-1-R transfected cells. In mice, injection of the hybrid in combination with glucose significantly (P < 0.001) reduced glucose and increased insulin concentrations, with metabolic actions evident (P < 0.05) 8 h post-injection. Twice-daily injection of N-ac(d-Ala2)GIP/GLP-1-exe to high fat fed (HFF) mice for 28 days significantly (P < 0.05-P < 0.001) reduced body weight, HbA1c, circulating glucose and insulin concentrations. Furthermore, both oral and i.p. glucose tolerance were improved (P < 0.001) and insulin sensitivity enhanced. The hybrid peptide also increased (P < 0.05-P < 0.001) beta cell number, islet area, pancreatic insulin content and islet insulin secretory responsiveness in HFF mice. Finally, N-ac(d-Ala2)GIP/GLP-1-exe treated mice exhibited improved (P < 0.01) recognition memory which was accompanied by enhanced (P < 0.05-P < 0.001) hippocampal neurogenesis, synapse formation and reduced neuronal oxidative stress. These data demonstrate for the first time the beneficial actions of the novel GIP/GLP-1 hybrid, N-ac(d-Ala2)GIP/GLP-1-exe, on glucose homeostasis and memory function in diabetes.


Subject(s)
Hypoglycemic Agents/pharmacology , Incretins/agonists , Neuroprotective Agents/pharmacology , Peptide Fragments/pharmacology , Amino Acid Sequence , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , CHO Cells , Cricetinae , Cricetulus , Diet, High-Fat/adverse effects , HEK293 Cells , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Hypoglycemic Agents/chemistry , Incretins/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Mice , Neuroprotective Agents/chemistry , Oxidative Stress/drug effects , Oxidative Stress/physiology , Peptide Fragments/chemistry , Peptide Fragments/genetics
9.
J Public Health (Oxf) ; 39(3): 455-463, 2017 09 01.
Article in English | MEDLINE | ID: mdl-27591301

ABSTRACT

Background: There is evidence that key health behaviours of people who migrate deteriorate over time, which has a consequent impact upon the health of dependent children. As health in the early years sets the course for lifelong health, it is important to explore parents' views on maintaining children's health following migration. Methods: Five focus groups were held with parents of preschool children who had migrated to the UK within the last 10 years (n = 28). Parents originated from Romania, Poland, Somalia and Pakistan, with one group of Roma Gypsy parents. Data collection took place in January to March 2015. Results: All groups, apart from the Roma, perceived barriers to maintaining optimal health and well-being for their preschool children following migration to the UK. Eastern European parents experienced difficulties in ensuring family financial security, while parents from more established communities focused on barriers to children's exercise, play and nutrition. Conclusions: This study highlights aspects of public health where migrants and their children can experience adverse effects in the UK. These findings have implications for policymakers, commissioners and providers of health services who aim to promote good health among preschool children.


Subject(s)
Attitude to Health , Child Health , Parents/psychology , Transients and Migrants/psychology , Adolescent , Adult , Child, Preschool , Female , Focus Groups , Health Behavior , Humans , Male , Middle Aged , Pakistan/ethnology , Poland/ethnology , Qualitative Research , Roma/ethnology , Roma/psychology , Romania/ethnology , Somalia/ethnology , United Kingdom
10.
Org Biomol Chem ; 14(39): 9278-9286, 2016 Oct 04.
Article in English | MEDLINE | ID: mdl-27722734

ABSTRACT

Antimicrobial Peptides (AMPs) have unique anticancer properties, but their clinical application is currently limited by an inadequate margin of safety. A prodrug strategy associated with a combination therapy approach could address this limitation by increasing their therapeutic index and their efficacy. Accordingly, the first targeted anticancer polymeric prodrug candidates of AMPs, intended for combination therapy with another polymeric prodrug of an approved antineoplastic agent (doxorubicin), were synthesized as either a PEG-based dual-release prodrug or two individual pegylated prodrugs. The latter are based on a cathepsin B-labile peptide linker and an acid-sensitive acyl hydrazone bond for the AMP and doxorubicin prodrugs, respectively. Anticancer activities and toxicity differentials achieved with the free peptide and its polymer conjugates against ovarian, cancer and non-malignant, cells, indicate that protease-dependent reversible pegylation could be implemented to increase the therapeutic indices of AMPs in cancer therapy. The results obtained also show that this approach can be developed if the releasable PEG linker can be optimised to conciliate the attributes and restrictions of pegylation against proteases. In addition, combination of the polymeric prodrugs of the AMP and of doxorubicin provides additive antitumor effects which could be exploited to enhance the efficacy of the AMP candidate.


Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Prodrugs/chemistry , Antimicrobial Cationic Peptides/chemistry , Antineoplastic Combined Chemotherapy Protocols/chemistry , Cathepsin B/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Screening Assays, Antitumor/methods , Humans , Polyethylene Glycols/chemistry , Polymers/chemistry , Prodrugs/chemical synthesis , Prodrugs/pharmacology
11.
Biometals ; 28(2): 367-80, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25725797

ABSTRACT

Burkholderia cenocepacia is a bacterial pathogen which causes severe respiratory infections in cystic fibrosis (CF). These studies were aimed at gaining an insight into the iron acquisition strategies of B. cenocepacia. In iron restricted conditions, genes associated with the synthesis and utilisation of ornibactin (pvdA, orbA, orb F) were significantly upregulated compared to the expression of pyochelin associated genes (pchD, fptA). In the absence of alternative iron sources, B. cenocepacia J2315 and 715j utilised ferritin and haemin, but not transferrin or lactoferrin for growth. Significantly, mutants unable to produce ornibactin, (715j-orbI) or ornibactin and pyochelin, (715j-pobA), utilised haemin and ferritin more efficiently than the wild-type. Moreover, both mutants were also able to utilise lactoferrin for growth (P ≤ 0.01) and additionally 715j-pobA utilised transferrin (P ≤ 0.01), potentially facilitating adaptation to the host environment. Furthermore, B. cenocepacia increased ornibactin gene expression in response to pyoverdine from Pseudomonas aeruginosa (P ≤ 0.01), demonstrating the capacity to compete for iron in co-colonised niches. Pyoverdine also significantly diminished the growth of B. cenocepacia (P < 0.001) which was related to its iron chelating activity. In a study of three B. cenocepacia sequential clonal isolates obtained from a CF patient over a 3.5 year period, ornibactin upregulation in response to pyoverdine was less pronounced in the last isolate compared to the earlier isolates, as was growth in the presence of haemin and ferritin, indicating alternative iron acquisition mechanism(s) may dominate as chronic infection progresses. These data demonstrate the multifaceted iron acquisition strategies of B. cenocepacia and their capacity to be differentially activated in the presence of P. aeruginosa and during chronic infection.


Subject(s)
Burkholderia cenocepacia/metabolism , Iron/metabolism , Siderophores/genetics , Adaptation, Physiological , Burkholderia Infections/microbiology , Burkholderia cenocepacia/genetics , Cystic Fibrosis/microbiology , Gene Expression , Gene Expression Regulation, Bacterial , Genes, Bacterial , Heme/metabolism , Humans , Pneumonia, Bacterial/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/physiology , Siderophores/biosynthesis , Transcriptional Activation
12.
Neurogastroenterol Motil ; 26(3): 316-25, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24286617

ABSTRACT

BACKGROUND: Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms. METHODS: Junctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence. KEY RESULTS: E-cadherin and ZO-1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1 expression was not significantly altered compared with controls. On subtype analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E-cadherin expression was associated with longer symptoms duration specifically in IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but this association was unrelated to IBS subtype. CONCLUSIONS & INFERENCES: E-cadherin protein expression in the cecum was significantly lower in IBS-A compared with controls and associated with longstanding symptoms. E-cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E-cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS.


Subject(s)
Cadherins/metabolism , Cecum/metabolism , Irritable Bowel Syndrome/metabolism , Abdominal Pain/metabolism , Adult , Claudin-1/metabolism , Diarrhea/metabolism , Female , Humans , Male , Middle Aged , Zonula Occludens-1 Protein/metabolism
13.
QJM ; 105(7): 665-73, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22383688

ABSTRACT

BACKGROUND: Although Thrombolysis has been licensed in the UK since 2003, it is still administered only to a small percentage of eligible patients. AIM: We consider the impact of investing the impact of thrombolysis on important acute stroke services, and the effect on quality of life. The concept is illustrated using data from the Northern Ireland Stroke Service. DESIGN: Retrospective study. METHODS: We first present results of survival analysis utilizing length of stay (LOS) for discharge destinations, based on data from the Belfast City Hospital (BCH). None of these patients actually received thrombolysis but from those who would have been eligible, we created two initial groups, the first representing a scenario where they received thrombolysis and the second comprising those who do not receive thrombolysis. On the basis of the survival analysis, we created several subgroups based on discharge destination. We then developed a discrete event simulation (DES) model, where each group is a patient pathway within the simulation. Coxian phase type distributions were used to model the group LOS. Various scenarios were explored focusing on cost-effectiveness across hospital, community and social services had thrombolysis been administered to these patients, and the possible improvement in quality of life, should the proportion of patients who are administered thrombolysis be increased. Our aim in simulating various scenarios for this historical group of patients is to assess what the cost-effectiveness of thrombolysis would have been under different scenarios; from this we can infer the likely cost-effectiveness of future policies. RESULTS: The cost of thrombolysis is offset by reduction in hospital, community rehabilitation and institutional care costs, with a corresponding improvement in quality of life. CONCLUSION: Our model suggests that provision of thrombolysis would produce moderate overall improvement to the service assuming current levels of funding.


Subject(s)
Models, Econometric , Stroke/drug therapy , Thrombolytic Therapy/statistics & numerical data , Aged , Cost-Benefit Analysis , Drug Costs/statistics & numerical data , Female , Fibrinolytic Agents/economics , Fibrinolytic Agents/therapeutic use , Health Care Costs/statistics & numerical data , Hospitals, Public/statistics & numerical data , Humans , Kaplan-Meier Estimate , Length of Stay/statistics & numerical data , Male , Middle Aged , Northern Ireland/epidemiology , Quality of Life , Quality-Adjusted Life Years , Retrospective Studies , Stroke/economics , Stroke/mortality , Thrombolytic Therapy/economics
14.
Diabet Med ; 27(6): 650-4, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20546282

ABSTRACT

AIMS: To review postpartum glucose tolerance in women with gestational diabetes and evaluate the role of formal 75 g oral glucose tolerance testing vs. fasting plasma glucose in screening for persistent abnormalities. METHODS: Retrospective study of 985 pregnancies over a 10 year period in a mixed ethnic cohort of women who underwent follow-up glucose tolerance testing at 6 weeks postpartum. Diagnosis obtained by oral glucose tolerance test was tested against that from the fasting plasma glucose value. RESULTS: There were 272 abnormal postpartum oral glucose tolerance test results (27.6%), with 109 women identified as having frank diabetes. Eleven of these (10%) had fasting plasma glucose < or =6.0 mmol/l, as did 62 of 114 cases of impaired glucose tolerance. A fasting plasma glucose concentration of > or =6.1 mmol/l correctly identified abnormal glucose tolerance in 199 of 272 cases (sensitivity 0.73). South Asian women were much more likely to have persistent abnormalities of glucose tolerance than were Europeans (32 vs. 15%, chi(2)P < 0.0001). CONCLUSIONS: A postpartum fasting plasma glucose measurement alone is not sensitive enough in our population to classify glucose tolerance status accurately. A formal postpartum oral glucose tolerance test is therefore needed to facilitate early detection and treatment.


Subject(s)
Diabetes Mellitus/diagnosis , Diabetes, Gestational/diagnosis , Postpartum Period/physiology , Adult , Blood Glucose/analysis , Ethnicity , Female , Glucose Tolerance Test/methods , Humans , Postpartum Period/blood , Predictive Value of Tests , Pregnancy , Retrospective Studies , Risk Factors , Time Factors
15.
Lett Appl Microbiol ; 50(5): 500-6, 2010 May.
Article in English | MEDLINE | ID: mdl-20337933

ABSTRACT

AIMS: To develop a rapid method to quantify the attachment of the cystic fibrosis pathogen, Burkholderia multivorans, to lung epithelial cells (16HBE14o(-)) using real-time PCR with a view to monitoring potential inhibition of lung cell attachment. METHODS AND RESULTS: Mammalian and bacterial DNA were purified from bacteria attached to lung epithelial cells. The relative amount of bacteria attached was determined by amplification of the recA gene relative to the human GAPDH gene, in the presence of SYBR Green. The method was thoroughly validated and shown to correlate well with traditional plating techniques. Inhibition of bacterial attachment with simple sugars was then evaluated by real-time PCR. Of the sugars examined, pre-incubation of B. multivorans with lactose, mannose and xylitol all decreased bacterial adherence to 16HBE14o(-) cells, while glucose and galactose had no significant effect. Pre-incubation with lactose had the greatest effect, resulting in reduced adhesion to 35% of untreated controls. CONCLUSIONS: This method can be used to quickly and effectively screen novel agents with higher affinities for bacterial adhesins. SIGNIFICANCE AND IMPACT OF THE STUDY: This method will enable the rapid development of novel agents to inhibit colonization by this pathogen from the environment.


Subject(s)
Bacterial Adhesion/drug effects , Burkholderia Infections/microbiology , Burkholderia cepacia complex/isolation & purification , Burkholderia cepacia complex/physiology , Epithelial Cells/microbiology , Lung/microbiology , Polymerase Chain Reaction/methods , Burkholderia cepacia complex/drug effects , Burkholderia cepacia complex/genetics , Carbohydrates/pharmacology , Cell Line , Humans , Lung/cytology
16.
Qual Saf Health Care ; 17(5): 382-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18842980

ABSTRACT

BACKGROUND: With healthcare, Lean Thinking encounters a world, not devoid of value, but awash with sophisticated and mutually unconnected concepts of value. DESIGN: Given a shortage of systematic analysis in the literature, this paper provides a preliminary analysis of areas where the read-across from other sectors to healthcare is relatively well understood, based on a broad review of its impact on care delivery. It further proposes areas where conceptual development is needed. In particular, healthcare, with its many measures of value, presents an unusual challenge to the central Lean driver of value to the customer. CONCLUSION: We conclude that there is scope for methodological development, perhaps by defining three themes associated with value-the operational, the clinical and the experiential.


Subject(s)
Critical Pathways , Delivery of Health Care/methods , State Medicine/organization & administration , Systems Analysis , Total Quality Management , Delivery of Health Care/standards , Efficiency, Organizational , Health Services Research , Humans , United Kingdom
17.
Eur J Clin Microbiol Infect Dis ; 26(12): 869-77, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17874328

ABSTRACT

The Burkholderia cepacia complex (Bcc) is a group of ten closely related species associated with life-threatening infection in cystic fibrosis (CF). These bacteria are highly antibiotic resistant, with some strains transmissible, and in a subgroup of patients, they can cause a rapid and fatal necrotising pneumonia. The Bcc organisms produce a range of exoproducts with virulence potential, including exopolysaccharide, proteases and lipases. Many members of the Bcc are also capable of epithelial cell invasion, although the mechanism(s) involved are poorly understood. This study investigates a role for Bcc lipase in epithelial cell invasion by Bcc strains. Lipase activity was measured in eight species of the Bcc. Strains that produced high levels of lipase were predominantly from the B. multivorans and B. cenocepacia species. Pre-treatment of two epithelial cell lines with Bcc lipase significantly increased invasion by two B. multivorans strains and one B. cenocepacia strain and did not affect either plasma membrane or tight junction integrity. Inhibition of Bcc lipase production by the lipase inhibitor Orlistat significantly decreased invasion by both B. multivorans and B. cenocepacia strains in a concentration-dependent manner. This study demonstrates the extent of lipase production across the Bcc and establishes a potential role for lipase in Bcc epithelial cell invasion.


Subject(s)
Bronchi/cytology , Burkholderia cepacia complex/enzymology , Epithelial Cells/microbiology , Lipase/metabolism , Cell Line , Cell Membrane/metabolism , Enzyme Inhibitors/pharmacology , Humans , Lactones/pharmacology , Lipase/antagonists & inhibitors , Orlistat , Tight Junctions/metabolism
18.
Eur J Clin Microbiol Infect Dis ; 26(3): 213-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17265071

ABSTRACT

This study determined the antibiotic susceptibility of planktonic and biofilm cultures of Burkholderia cepacia complex organisms, a group of highly problematic pathogens associated with cystic fibrosis patients. The biofilm inhibitory concentrations were considerably higher than the corresponding minimum inhibitory concentrations for meropenem and piperacillin-tazobactam. However, tobramycin and amikacin were efficacious against both biofilm and planktonic cultures. Overall this study showed that biofilm susceptibility testing might be more clinically appropriate for determining antibiotic therapy for Burkholderia cepacia complex infections in cystic fibrosis patients.


Subject(s)
Biofilms/growth & development , Burkholderia cepacia complex/drug effects , Burkholderia cepacia complex/physiology , Plankton/growth & development , Burkholderia cepacia complex/growth & development , Drug Resistance, Bacterial , Microbial Sensitivity Tests
19.
Methods Inf Med ; 44(3): 369-73, 2005.
Article in English | MEDLINE | ID: mdl-16113759

ABSTRACT

OBJECTIVES: To show that Markov chain modelling can be applied to data on geriatric patients and use these models to assess the effects of covariates. METHODS: Phase-type distributions were fitted by maximum likelihood to data on times spent by the patients in hospital and in community-based care. Data on the different events that ended the patients' periods of care were used to estimate the dependence of the probabilities of these events on the phase from which the time in care ended. The age of the patients at admission to care and the year of admission were also included as covariates. RESULTS: Differential effects of these covariates were shown on the various parameters of the fitted model, and interpretations of these effects made. CONCLUSIONS: Models based on phase-type distributions were appropriate for describing times spent in care, as the ordered phases had an interpretable structure corresponding to increasing amounts of care being given.


Subject(s)
Community Health Services/statistics & numerical data , Geriatrics/organization & administration , Hospitals, Public/statistics & numerical data , Markov Chains , Models, Statistical , Aged , Aged, 80 and over , Fuzzy Logic , Geriatrics/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Likelihood Functions , London , Male , Mortality , Severity of Illness Index
20.
Conf Proc IEEE Eng Med Biol Soc ; 2005: 7568-71, 2005.
Article in English | MEDLINE | ID: mdl-17282032

ABSTRACT

In this work, a method that combines wavelet transform and Bayesian network is developed for the classification of the auditory brainstem response (ABR). First the wavelet transform is applied to extract the important features of the ABR by thresholding and matching the wavelet coefficients. A Bayesian network is then built up based on several variables obtained from these significant wavelet coefficients. In order to evaluate the performance of this approach, stratified 10-fold cross-validation is used and the network is evaluated on subject-dependent test sets (drawn from the same subjects from which the training set was derived). In particular, the data analyzed here are the ABR data with only fewer repetitions (64 or 128 repetitions) and this offers the great advantage of reducing the total time of recording, which is very beneficial to both the clinicians and the patients. Finally, a preprocessing method based on Woody averaging is applied to adjust the latency shift of the ABR data and it enhances the results.

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