345 research outputs found

    Characterisation of the flaviviral non-structural protein NS1'

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    The effectiveness of clinical networks in improving quality of care and patient outcomes: a systematic review of quantitative and qualitative studies.

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    BACKGROUND: Reorganisation of healthcare services into networks of clinical experts is increasing as a strategy to promote the uptake of evidence based practice and to improve patient care. This is reflected in significant financial investment in clinical networks. However, there is still some question as to whether clinical networks are effective vehicles for quality improvement. The aim of this systematic review was to ascertain the effectiveness of clinical networks and identify how successful networks improve quality of care and patient outcomes. METHODS: A systematic search was undertaken in accordance with the PRISMA approach in Medline, Embase, CINAHL and PubMed for relevant papers between 1 January 1996 and 30 September 2014. Established protocols were used separately to examine and assess the evidence from quantitative and qualitative primary studies and then integrate findings. RESULTS: A total of 22 eligible studies (9 quantitative; 13 qualitative) were included. Of the quantitative studies, seven focused on improving quality of care and two focused on improving patient outcomes. Quantitative studies were limited by a lack of rigorous experimental design. The evidence indicates that clinical networks can be effective vehicles for quality improvement in service delivery and patient outcomes across a range of clinical disciplines. However, there was variability in the networks' ability to make meaningful network- or system-wide change in more complex processes such as those requiring intensive professional education or more comprehensive redesign of care pathways. Findings from qualitative studies indicated networks that had a positive impact on quality of care and patients outcomes were those that had adequate resources, credible leadership and efficient management coupled with effective communication strategies and collaborative trusting relationships. CONCLUSIONS: There is evidence that clinical networks can improve the delivery of healthcare though there are few high quality quantitative studies of their effectiveness. Our findings can provide policymakers with some insight into how to successfully plan and implement clinical networks by ensuring strong clinical leadership, an inclusive organisational culture, adequate resourcing and localised decision-making authority

    HYPOGLYCEMIC, ANTI-INFLAMMATORY EFFECT OF PORANG (AMORPHOPHALLUS ONCHOPYLLUS) ON ALLOXAN-INDUCED DIABETIC RATS

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    Introduction: Iles-iles / Porang is a tuber-producing plant that is commonly found in Indonesia. One of the most sought after content from Porang is Glucomannan. One of Porang’s health benefit is related to the effect of lowering blood glucose levels because it can prevent glucose absorption. These benefit is interesting to study because there has been no research linking the use of Porang to reduce inflammatory process in hyperglycmic conditions. Purpose: This study aims to analyze the anti-inflammatory, anti-oxidant and hypoglycemis effects of Glucomannan from Porang (Amorphophallus onchophyllus) extract in experimental animals. Method: The research design was a true experimental post-test only control group with random sampling to determine 5 white rats into the normal group, positive control group, negative control group and treatment 1, 2 and 3. The positive control group received Acarbose therapy thile the negative control group received carboxy-methyl-cellulose (CMC) therapy. This study used Porang extract (Amorphophallus onchophyllus) with concentrations of 200, 400 and 800 mg/Kg in hyperglycemic white rats that had been induced by Aloxan. The study was conducte for 50 days and then blood and serum samples were taken to assess the effect of hypoglycemia, anti-inflammatory and anti-oxidant using blood glucose, Malondialdehyde and C-reactiveprotein (CRP) measurement. Result and Discussion: The results showed no significant difference between the groups of rats receiving Porang extract and the positive and negative control groups. However, the MDA levels after 50 days of intervention between the negative control group and the therapy with doses of 200, 400 and 800 mg/Kg showed significant differences. Similarly found for blood glucose levels after intervention between negative control group and the 200 and 400 mg/Kg therapy group. This results may be caused by the type of Porang used, the form of the Porang and the concentration level of the Porang extract. Conclusion: Porang with the type of Amorphophallus onchophyllus can’t be used directly, but requires further processing to obtain the active substance Glucomannan

    Cigarette smoke exposure redirects Staphylococcus aureus to a virulence profile associated with persistent infection

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    Altres ajuts: This work also received a grant from the Spanish Society of Pneumology and Thoracic Surgery (SEPAR 024/2016). M.L. gratefully acknowledges funding from the European Respiratory Society Long-term Fellowship grant (LTRF-5934). A.M.E. acknowledges funding from the Royal Society, Department of Medicine (Imperial College), and from the Imperial NIHR Biomedical Research Centre, Imperial College London. B.C.Y is funded by an NIHR Clinical Lectureship. CP acknowledges Programa Germans Trias Sapiens Fundació Catalunya la Pedrera and European Respiratory Society short term research fellowship October 2018 (STRTF201810-00467).Tobacco smoking represents the leading preventable cause of death worldwide. Smoking is a recognised risk factor for several pathologies and is detrimental to host immune surveillance and defence. However, the impact of smoking on microbial residents of the nasopharyngeal cavity, in contact with cigarette smoke (CS), is lacking. Staphylococcus aureus is a major human pathogen that colonises the human nasopharynx and causes a wide range of infections. We investigated the impact of CS on specific virulence phenotypes important in S aureus pathogenesis. We observed strain-dependent differences following exposure to CS, namely growth inhibition, augmented biofilm formation, increased invasion of, and persistence within, bronchial alveolar epithelial cells. Additionally, we confirm the critical role of a functional accessory gene regulator (Agr) system in mediating increased biofilm development and host cell invasion and persistence following CS exposure. Furthermore, CS exposure resulted in reduced toxin production. Importantly, exposure of S aureus to CS accelerated the frequency of mutations and resulted in a significant increase in gentamicin-resistant small colony variant (SCV) formation. Mutational analysis revealed that CS induced SCVs emerge via the SOS response DNA mutagenic repair system. Taken together, our results suggest that CS redirects certain S aureus strains to a virulence profile associated with persistence

    Understanding how satisfactory service relationships can be mutually beneficial in the higher education context

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    Purpose While extant research has predominantly focused on outcomes of customer satisfaction that benefit the focal firm such as customer engagement behaviors (CEBs), little is done to understand human capital-related outcomes that directly benefit customers and thus benefit the firm indirectly. Drawing on the theory of reasoned action, broaden-and-build theory of positive emotions and human capital theory, this study aims to understand how and why a satisfied customer benefits the firm directly (CEBs) and indirectly (human capital-related outcomes). Design/methodology/approach Following a sequential mixed-methods approach, two studies are conducted in an extended service encounter context (higher education) where customers also constitute key human capital of the service firm. First, a qualitative study is conducted, which is then followed by a quantitative study. Survey data collected from students working as interns in organizations and their immediate managers resulted in 209 “intern–manager” dyads. Findings The findings demonstrate that customer satisfaction on its own does not substantially account for either human capital-related outcomes or CEBs (except word of mouth [WOM]). Both emotional and cognitive mechanisms play key and unique mediating roles in translating satisfaction into outcomes that benefit a service firm directly and indirectly by benefiting its customers. Research limitations/implications While much research demonstrates benefits of customer satisfaction for the focal firm, this research advances our understanding of the novel consequences of customer satisfaction by shedding light on human capital-related outcomes that directly benefit customers. It also aids in explicating prior inconsistent findings on the relationship between customer satisfaction and CEBs by uncovering the underlying mediating mechanisms. Practical implications This investigation provides a deeper understanding of the significance of customer satisfaction by demonstrating how and why satisfied customers increase firm value beyond purchase, for instance, by being direct (through positive WOM) and indirect (through enhanced human capital performance) promoters, consultants (through participation) or investors (through monetary giving). A key implication of this research is that simply enhancing customer satisfaction on its own may not suffice as the findings suggest that satisfaction translates into beneficial outcomes only when satisfaction is channeled toward enhancing customer perceptions of competence and their positive emotions. Originality/value This study contributes to the literature by providing a deeper understanding of how and why customer satisfaction influences outcomes that not only benefit the firm but also its customers in extended service encounter context

    Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

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    Staphylococcus aureus is a commensal and frequent colonizer of the upper respiratory tract. When mechanical ventilation disrupts natural defenses, S. aureus is frequently isolated from the lower airways, but distinguishing between colonization and infection is difficult. The objectives of this study were (1) to investigate the bacterial genome sequence in consecutive isolates in order to identify changes related to the pathological adaptation to the lower respiratory tract and (2) to explore the relationship between specific phenotypic and genotypic features with the patient's study group, persistence of the clinical isolate and clinical outcome. A set of 94 clinical isolates were selected and corresponded to 34 patients that were classified as having pneumonia (10), tracheobronchitis (11) and bronchial colonization (13). Clinical strains were phenotypically characterized by conventional identification and susceptibility testing methods. Isolates underwent whole genome sequencing using Illumina HiSeq4000. Genotypic characterization was performed with an in-house pipeline (BacterialTyper). Genomic variation arising within-host was determined by comparing mapped sequences and de novo assemblies. Virulence factors important in staphylococcal colonization and infection were characterized using previously established functional assays. (1) Toxin production was assessed using a THP-1 cytotoxicity assay, which reports on the gross cytotoxicity of individual isolates. In addition, we investigated the expression of the major virulence factor, alpha-toxin (Hla) by Western blot. (2) Adhesion to the important extracellular matrix molecule, fibronectin, was determined using a standardized microtitre plate assay. Finally, invasion experiments using THP-1 and A539 cell lines and selected clinical strains were also performed. Repeated isolation of S. aureus from endotracheal aspirate usually reflects persistence of the same strain. Within-host variation is detectable in this setting, but it shows no evidence of pathological adaptation related to virulence, resistance or niche adaptations. Cytotoxicity was variable among isolates with 14 strains showing no cytotoxicity, with these latter presenting an unaltered Fn binding capacity. No changes on cytotoxicity were reported when comparing study groups. Fn binding capacity was reported for almost all strains, with the exception of two strains that presented the lowest values. Strains isolated from patients with pneumonia presented a lower capacity of adhesion in comparison to those isolated during tracheobronchitis (p = 0.002). Hla was detected in 71 strains (75.5%), with most of the producer strains in pneumonia and bronchial colonization group (p = 0.06). In our cohort, Hla expression (presence or absence) in sequential isolates was usually preserved (70%) although in seven cases the expression varied over time. No relationship was found between low cytotoxicity and intracellular persistence in invasion experiments. In our study population, persistent S. aureus isolation from airways in ventilated patients does not reflect pathological adaptation. There is an important diversity of sequence types. Cytotoxicity is variable among strains, but no association with study groups was found, whereas isolates from patients with pneumonia had lower adhesion capability. Favorable clinical outcome correlated with increased bacterial adhesion in vitro. Most of the strains isolated from the lower airways were Hla producers and no correlation with an adverse outcome was reported. The identification of microbial factors that contribute to virulence is relevant to optimize patient management during lower respiratory tract infections

    Patterns of care and outcomes for a clinical cohort of patients with lung cancer (2016-2021): Report on the Embedding Research (and Evidence) in Cancer Healthcare – EnRICH Program

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    Despite advances in diagnosis and treatment, lung cancer continues to be the leading cause of cancer-related death in Australia. Survival outcomes remain disappointing with less than a quarter of patients (22%) alive five years after diagnosis. Strategies to improve lung cancer care have focused on more rapid diagnosis and treatment from initial symptom presentation; a greater use of combined modalities of therapy; novel approaches using molecular-based diagnostics, targeted therapies, and immunotherapies; as well as a greater use of supportive and palliative care. The Embedding Research (and Evidence) in Cancer Healthcare (EnRICH) Program has explored patterns of care and clinical outcomes in a cohort of 2000 real-world patients presenting to six major specialist cancer centres in NSW with a first diagnosis between September 2016 and October 2021. This report provides valuable information on the natural history of patients following their initial diagnosis and maps out the use of evidence-based care, as well as identifying important factors defining overall prognosis. The report identifies that tumour stage at diagnosis remains one of the most important prognostic factors for both non-small cell (NSCLC) and small cell (SCLC) lung cancer. In NSCLC, stage, age, sex, performance status, co-morbid illness, neutrophil to lymphocyte ratio, haemoglobin levels, non-English speaking background, and mutation status are each independent factors predicting survival outcomes. Stage, performance status, and neutrophil to lymphocyte ratio are also predictive of survival in SCLC lung cancer. Overall, patients at major specialist cancer centres in NSW have done relatively well compared with other Australian cohorts such as those included in the Victorian Lung Cancer Registry and the Queensland Lung Cancer Quality Index, but it is important to note that the EnRICH cohort only includes those seen at least once at a major specialist cancer centre and does not represent all patients with lung cancer in these regions – a topic being further investigated in a subsequent report. Several quality indicators of cancer care are being captured and fed back to NSW practitioners and health administrators to inform practice and service development. While these indicators are comparable with other regions, there remain areas for improvement - a focus of ongoing work. Reassuringly, quality of care and outcomes for patients in the EnRICH cohort were not adversely affected by health service disruptions during the COVID-19 pandemic. Through this effort we hope to better document current outcomes of patients with lung cancer and the care they receive with the aim of improving current evidence-based care and accelerating the uptake of new emerging evidence

    Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

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    Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts

    Psychometric properties of the Problematic Internet Use Questionnaire Short-Form (PIUQ-SF-6) in a nationally representative sample of adolescents

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    Despite the large number of measurement tools developed to assess problematic Internet use, numerous studies use measures with only modest investigation into their psychometric properties. The goal of the present study was to validate the short (6-item) version of the Problematic Internet Use Questionnaire (PIUQ) on a nationally representative adolescent sample (n = 5,005; mean age 16.4 years, SD = 0.87) and to determine a statistically established cut-off value. Data were collected within the framework of the European School Survey Project on Alcohol and Other Drugs project. Results showed an acceptable fit of the original three-factor structure to the data. In addition, a MIMIC model was carried out to justify the need for three distinct factors. The sample was divided into users at-risk of problematic Internet use and those with no-risk using a latent profile analysis. Two latent classes were obtained with 14.4% of adolescents belonging to the at-risk group. Concurrent and convergent validity were tested by comparing the two groups across a number of variables (i.e., time spent online, academic achievement, self-esteem, depressive symptoms, and preferred online activities). Using the at-risk latent profile analysis class as the gold standard, a cut-off value of 15 (out of 30) was suggested based on sensitivity and specificity analyses. In conclusion, the brief version of the (6-item) PIUQ also appears to be an appropriate measure to differentiate between Internet users at risk of developing problematic Internet use and those not at risk. Furthermore, due to its brevity, the shortened PIUQ is advantageous to utilize within large-scale surveys assessing many different behaviors and/or constructs by reducing the overall number of survey questions, and as a consequence, likely increasing completion rates

    A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events

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    Background. Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predict diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. Results. Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent datasets from Europe and the US. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). Conclusions. We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures
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