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1.
Acad Med ; 95(7): 980-983, 2020 07.
Article in English | MEDLINE | ID: mdl-32079958

ABSTRACT

Public trust in physicians has declined over the last 50 years. Future physicians will need to mend the patient-physician trust relationship. In conjunction with the American Medical Association's Accelerating Change in Medical Education initiative, the Mayo Clinic Alix School of Medicine implemented the Science of Health Care Delivery (SHCD) curriculum-a 4-year curriculum that emphasizes interdisciplinary training across population-centered care; person-centered care; team-based care; high-value care; leadership; and health policy, economics, and technology-in 2015. In this medical student perspective, the authors highlight how the SHCD curriculum has the potential to address issues that have eroded patient-physician trust. The curriculum reaches this aim through didactic and/or experiential teachings in health equity, cultural humility and competence, shared decision making, patient advocacy, and safety and quality of care. It is the authors' hope that novel medical education programs such as the SHCD curriculum will allow the nation's future physicians to own their role in rebuilding and fostering public trust in physicians and the health care system.


Subject(s)
Education, Medical/methods , Physician-Patient Relations/ethics , Students, Medical/psychology , Trust/psychology , Cultural Diversity , Curriculum/trends , Decision Making, Shared , Delivery of Health Care/standards , Health Policy/legislation & jurisprudence , Humans , Leadership , Mental Competency , Patient Advocacy/education , Patient-Centered Care/standards , Physicians , Problem-Based Learning/methods , Quality of Health Care , Students, Medical/statistics & numerical data
2.
Rev Sci Tech ; 39(3): 663-673, 2020 Jan.
Article in English | MEDLINE | ID: mdl-35275143

ABSTRACT

Advances in information technologies (ITs) and operational technologies (OTs) offer high-containment laboratories opportunities to evolve scientific and operational approaches, while increasing efficiency. Emerging technologies steadily introduce changes in data generation and management practices. United States (US) government agencies and partners operate high-containment laboratories that rely on ITs/OTs to provide critical scientific functions that support prevention, detection, response and recovery for catastrophic events. These unique operating environments provide an opportunity for implementation of ITs/OTs that can facilitate both efficiency and deeper or parallel study of disease and associated biological phenomena. Operational study by subject matter experts can aid in identification of requirements and challenges pertaining to emerging ITs/OTs, examination of use cases, refinement of technical specifications and optimisation of workflows. The National Bio and Agro-Defense Facility (NBAF) in the United States of America (USA), slated to be fully operational by 2023, will be a state-of-the-art research and diagnostic facility with Biosafety Level 2, 3 and 4 laboratories for the study of high-consequence transboundary animal pathogens and zoonotic diseases impacting public health. The NBAF will support the diagnosis of emerging diseases, development of countermeasures and transboundary animal disease training. Given the rapid emergence of IT/OT solutions, the authors used a case study approach to analyse and assess real-world, high-containment laboratory functions to help maximise efficiency in mission delivery for the NBAF and the broader high-containment laboratory network. The case study approach described here could be widely adapted to diverse situations characterised by a high rate of change to provide accurate, relevant workflow analyses and optimised recommendations.


Les progrès enregistrés dans les domaines des technologies de l'information (IT) et des technologies opérationnelles (OT) offrent aux laboratoires de confinement à haute sécurité la possibilité de faire évoluer leurs approches scientifiques et opérationnelles tout en gagnant en efficacité. Grâce à ces technologies émergentes, les pratiques de production et de gestion des données sont régulièrement affinées. Les organismes gouvernementaux étatsuniens et leurs partenaires exploitent des laboratoires de confinement à haute sécurité qui font appel aux IT/OT pour mettre en oeuvre des fonctionnalités scientifiques cruciales en appui de la prévention, la détection, l'intervention et le rétablissement en cas de catastrophes. Ces environnements opérationnels uniques offrent la possibilité d'introduire des applications IT/OT afin de faciliter aussi bien l'efficacité des opérations que l'étude plus approfondie ou concomitante d'une maladie et des phénomènes biologiques qui lui sont associés. Des études opérationnelles menées par des spécialistes peuvent contribuer à identifier les exigences et les défis liés aux IT/OT émergentes, à vérifier leurs utilisations concrètes, à affiner les spécifications techniques et à optimiser l'ordonnancement des opérations. Le National Bio and Agro-Defense Facility (NBAF) des états-Unis d'Amérique, qui devrait être pleinement opérationnel d'ici 2023, sera une institution de recherche et de diagnostic de pointe dotée de laboratoires de niveaux de biosécurité 2, 3 et 4 pour l'étude des agents pathogènes responsables de maladies animales transfrontalières à haut risque et des agents zoonotiques à fort impact sur la santé publique. Le NBAF contribuera au diagnostic des maladies émergentes et à l'élaboration de mesures de lutte ; il dispensera également des formations sur les maladies animales transfrontalières. Compte tenu du développement rapide des nouvelles solutions IT/OT, les auteurs ont mis au point une méthode d'études de cas pour l'analyse et l'évaluation des fonctionnalités concrètes des laboratoires de confinement à haute sécurité, destinée à maximiser l'efficacité des prestations du NBAF et du réseau plus large de laboratoires de confinement à haute sécurité. La méthode par études de cas décrite ici pourrait être largement adaptée à diverses situations caractérisées par un niveau élevé de changement, afin de fournir des analyses précises et pertinentes de l'ordonnancement des opérations et d'élaborer des recommandations optimisées.


Los adelantos de las tecnologías de la información (TI) y las tecnologías operativas (TO) ofrecen a los laboratorios de alta contención la posibilidad de transformar sus lógicas y procedimientos de trabajo científico y al mismo tiempo ganar en eficiencia. Progresivamente, a la estela de las nuevas tecnologías, los métodos empleados para generar y gestionar datos van evolucionando. Ciertos organismos públicos estadounidenses administran, junto con entidades colaboradoras, laboratorios de alta contención que dependen de las TI/TO para cumplir una serie de cometidos científicos fundamentales en apoyo de la prevención y detección de sucesos catastróficos, de la respuesta a ellos y de los subsiguientes procesos de recuperación. Estos excepcionales entornos de trabajo ofrecen la posibilidad de implantar TI/TO que a la vez aporten más eficiencia y faciliten un estudio más a fondo o en paralelo de as enfermedades y los fenómenos biológicos asociados a ellas. La realización de estudios operativos a cargo de especialistas en el tema puede ayudar a determinar las necesidades y dificultades que plantean las nuevas TI/TO, a examinar ejemplos de utilización, a afinar las especificaciones técnicas y a optimizar los procesos de trabajo. El órgano nacional de defensa biológica y agrícola (National Bio and Agro-Defense Facility, NBAF) de los Estados Unidos de América, que según las previsiones funcionará a pleno rendimiento en 2023, constituirá un avanzado dispositivo de investigación y diagnóstico al que estarán adscritos laboratorios de nivel 2, 3 y 4 de seguridad biológica para el estudio de agentes patógenos de los animales y enfermedades zoonóticas de carácter transfronterizo y de gran repercusión que afecten a la salud pública. El NBAF secundará el diagnóstico de enfermedades emergentes, la preparación de medidas de lucha y la formación sobre enfermedades animales transfronterizas. Teniendo en cuenta la velocidad a la que surgen soluciones de TI/TO, los autores recurrieron al estudio de ejemplos concretos para analizar y evaluar las funciones que cumplen en el mundo real los laboratorios de alta contención con el objetivo de ayudar al NBAF y a la red general de laboratorios de alta contención a ejercer su cometido con la máxima eficiencia. El método de trabajo aquí descrito, basado en el estudio de casos concretos, podría ser adaptado a diversas situaciones que se caractericen por un alto ritmo de transformaciones para efectuar análisis precisos y pertinentes de los procesos de trabajo y formular recomendaciones optimizadas.

3.
Eur J Cancer ; 107: 133-141, 2019 01.
Article in English | MEDLINE | ID: mdl-30576969

ABSTRACT

OBJECTIVE: The computer-adaptive test (CAT) of the European Organisation for Research and Treatment of Cancer (EORTC), the EORTC CAT Core, assesses the same 15 domains as the EORTC QLQ-C30 health-related quality of life questionnaire but with increased precision, efficiency, measurement range and flexibility. CAT parameters for estimating scores have been established based on clinical data from cancer patients. This study aimed at establishing the European Norm for each CAT domain based on general population data. METHODS: We collected representative general population data across 11 European Union (EU) countries, Russia, Turkey, Canada and the United States (n ≥ 1000/country; stratified by sex and age). We selected item subsets from each CAT domain for data collection (totalling 86 items). Differential item functioning (DIF) analyses were conducted to investigate cross-cultural measurement invariance. For each domain, means and standard deviations from the EU countries (weighted by country population, sex and age) were used to establish a T-metric with a European general population mean = 50 (standard deviation = 10). RESULTS: A total of 15,386 respondents completed the online survey (n = 11,343 from EU countries). EORTC CAT Core norm scores for all 15 countries were calculated. DIF had negligible impact on scoring. Domain-specific T-scores differed significantly across countries with small to medium effect sizes. CONCLUSION: This study establishes the official European Norm for the EORTC CAT Core. The European CAT Norm can be used globally and allows for meaningful interpretation of scores. Furthermore, CAT scores can be compared with sex- and age-adjusted norm scores at a national level within each of the 15 countries.


Subject(s)
Factor Analysis, Statistical , Health Status , Neoplasms/psychology , Quality of Life , Surveys and Questionnaires/standards , Adolescent , Adult , Aged , Algorithms , Europe/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/therapy , Psychometrics , Reference Values , Sickness Impact Profile , Young Adult
4.
Eur J Cancer ; 107: 153-163, 2019 01.
Article in English | MEDLINE | ID: mdl-30576971

ABSTRACT

OBJECTIVE: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 health-related quality of life questionnaire is one of the most widely used cancer-specific health-related quality of life questionnaires worldwide. General population norm data can facilitate the interpretation of QLQ-C30 data obtained from cancer patients. This study aimed at systematically collecting norm data from the general population to develop European QLQ-C30 norm scores and to generate comparable norm data for individual countries in Europe and North America. METHODS: We collected QLQ-C30 data from the general population across 11 European Union (EU) countries, Russia, Turkey, Canada and United States (n ≥ 1000/country). Representative samples were stratified by sex and age groups (18-39, 40-49, 50-59, 60-69 and ≥ 70 years). After applying weights based on the United Nations population distribution statistics, we calculated QLQ-C30 domain scores to generate a 'European QLQ-C30 Norm' based on the EU countries. Further, we calculated QLQ-C30 norm scores for all 15 individual countries. RESULTS: A total of 15,386 respondents completed the online survey. For the EU sample, most QLQ-C30 domains showed differences by sex/age, with men scoring somewhat better health than women, while age effects varied across domains. Substantially larger differences were seen in inter-country comparisons, with Austrian and Dutch respondents reporting consistently better health compared with British and Polish respondents. CONCLUSIONS: This study is the first to systematically collect EORTC QLQ-C30 general population norm data across Europe and North America applying a consistent data collection method across 15 countries. These new norm data facilitate valid intra-country as well as inter-country comparisons and QLQ-C30 score interpretation.


Subject(s)
Health Status , Models, Statistical , Neoplasms/psychology , Quality of Life , Surveys and Questionnaires/standards , Adolescent , Adult , Aged , Algorithms , Canada/epidemiology , Europe/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/therapy , North America/epidemiology , Psychometrics , Reference Values , Social Class , Young Adult
5.
Case Rep Dent ; 2018: 4850901, 2018.
Article in English | MEDLINE | ID: mdl-29967701

ABSTRACT

Periapical granuloma is a pathological diagnosis associated clinically and radiographically with a nonvital tooth and a periapical radiolucency, respectively. It is frequently seen as a sequela of long-standing pulpal necrosis. Often times, a draining fistula is observed near the nonvital tooth. We report an unusual case of a large draining focal fibrous hyperplasia in association with a large periapical granuloma treated at our clinic. The diagnosis was made by the clinical presentation, radiologic and histopathologic findings.

6.
ACS Biomater Sci Eng ; 4(1): 128-141, 2018 Jan 08.
Article in English | MEDLINE | ID: mdl-33418683

ABSTRACT

Electrodes implanted in the brain or spinal cord trigger the activation of resident astrocytes. In their reactive state, astrocytes surrounding the electrode form a glial scar, compromising the ability of the electrode to interface with the surrounding neural tissue. One approach to reduce the inhibiting scar tissue is to incorporate nanoarchitecture on the surface of the implanted materials to modify the astrocytic response. The incorporated nanoarchitecture changes both the surface characteristics and the material properties of the implant interface. We investigated the response of rat cortical astrocytes to nanoporous anodic aluminum oxide (AAO) surfaces. Astrocytes were seeded onto nonporous aluminum control surfaces and AAO surfaces with average nanopore diameters of 20 and 90 nm. The surfaces were characterized by assessing their nanomorphology, hydrophobicity, surface chemistry, mechanical properties, and surface roughness. For cell response characterization, calcein-based viability and adhesion studies were performed. Plasmid-assisted vinculin live cell imaging was done to characterize focal adhesion number and distribution. Immunocytochemistry was used to assess glial fibrillary acidic protein (GFAP) expression. We found that astrocyte adhesion was significantly higher on small pore surfaces compared to large pore surfaces. Astrocytes produced more focal adhesions (FA) and distributed these FA peripherally when cultured on small pore samples compared to the other groups. Astrocyte GFAP expression was lower when astrocytes were cultured on surfaces with small nanopores compared to the control and large pore surfaces. These results indicate that unique surface nanoporosities influence astrocyte adhesion and subsequent cellular response. The reduction in GFAP immunoreactivity exhibited by the smaller pore surfaces can improve the long-term performance of the implanted neurodevices, thus making them credible candidates as a coating material for neural implants.

7.
BMC Palliat Care ; 16(1): 72, 2017 Dec 12.
Article in English | MEDLINE | ID: mdl-29233123

ABSTRACT

BACKGROUND: Previous research in England showed that deprivation level of a person's place of residence affects the place of death and quality of care received at the end of life. People dying in their preferred place of death has also been shown to act as an indication for high quality of end of life care services and social equality. This study expands on current research to explore the effects of deprivation and place of residence on health related choices and place of death in Wales. METHODS: We used ten years combined mortality statistics from 2005 to 2014 and Welsh Index of Multiple Deprivation rankings for each lower super output area. After accounting for the population's age, the number of deaths in Hospital, Hospice, Home, Care Home, Psychiatric Units, and Elsewhere were compared across deprivation quintiles. RESULTS: Distribution of place of death was found to be concentrated in three places - hospital (60%), home (21%) and care home (13%). Results from this study shows a high number of hospital deaths, especially for more deprived areas, despite being the least preferred place of death. CONCLUSION: This is the first Welsh study investigating place of death in relation to deprivation, which could be of major importance to academics, end of life care providers and policy makers interested in to reduce health care inequality in Wales.


Subject(s)
Death , Residence Characteristics/classification , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Nursing Homes/organization & administration , Nursing Homes/statistics & numerical data , Residence Characteristics/statistics & numerical data , Wales
8.
Ann Oncol ; 28(11): 2874-2881, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28945875

ABSTRACT

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. METHODS: The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. RESULTS: The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. CONCLUSIONS: The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Quality of Life , Small Cell Lung Carcinoma/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/psychology , Combined Modality Therapy , Europe , Female , Follow-Up Studies , Health Status Indicators , Humans , International Agencies , Lung Neoplasms/complications , Lung Neoplasms/psychology , Male , Middle Aged , Pain Measurement , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/psychology , Surveys and Questionnaires , Treatment Outcome
9.
Br J Cancer ; 115(9): 1032-1038, 2016 Oct 25.
Article in English | MEDLINE | ID: mdl-27673364

ABSTRACT

BACKGROUND: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. METHODS: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. RESULTS: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. CONCLUSIONS: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.


Subject(s)
Bile Duct Neoplasms/psychology , Cholangiocarcinoma/psychology , Gallbladder Neoplasms/psychology , Quality of Life , Surveys and Questionnaires , Adult , Aged , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/therapy , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Female , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/therapy , Humans , Male , Middle Aged , Prognosis , Psychometrics , Reproducibility of Results , Treatment Outcome
10.
Adv Physiol Educ ; 40(2): 165-75, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27068991

ABSTRACT

The properties of blood and the relative ease of access to which it can be retrieved make it an ideal source to gauge different aspects of homeostasis within an individual, form an accurate diagnosis, and formulate an appropriate treatment regime. Tests used to determine blood parameters such as the erythrocyte sedimentation rate, hemoglobin concentration, hematocrit, bleeding and clotting times, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean cell volume, and determination of blood groups are routinely used clinically, and deviations outside the normal range can indicate a range of conditions such as anemia, pregnancy, dehydration, overhydration, infectious disease, cancer, thyroid disease, and autoimmune conditions, to mention a few. As these tests can be performed relatively inexpensively and do not require high levels of technical expertise, they are ideally suited for use in the teaching laboratory, enabling undergraduate students to link theory to practice. The practicals described here permit students to examine their own blood and that of their peers and compare these with clinically accepted normal ranges. At the end of the practicals, students are required to answer a number of questions about their findings and to link abnormal values to possible pathological conditions by answering a series of questions based on their findings.


Subject(s)
Blood Physiological Phenomena/immunology , Health Education/methods , Hematologic Tests/methods , Problem-Based Learning/methods , Students, Health Occupations , Blood/immunology , Blood Sedimentation , Erythrocyte Count/methods , Erythrocyte Indices/physiology , Hematocrit/methods , Humans
12.
BMJ Support Palliat Care ; 6(3): 307-14, 2016 Sep.
Article in English | MEDLINE | ID: mdl-24943495

ABSTRACT

OBJECTIVES: To develop a model of the impact of cancer cachexia on patients by identifying the relevant health-related quality-of-life (HRQOL) issues, and to use the model to identify opportunities for intervention. METHODS: Standard systematic review methods were followed to identify papers which included direct quotes from cancer patients with cachexia or problems with eating or weight loss. Following thematic synthesis methodology, the quotes were coded, and themes and metathemes were extracted. The metathemes were used to develop a model of the patient's experience of cachexia. RESULTS: 18 relevant papers were identified which, in total, contained interviews with more than 250 patients. 226 patient quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes were formulated. The model developed from the metathemes demonstrated a direct link between eating and food problems and negative emotions and also a link mediated by the associated physical decline. These links provide opportunities for interventions. CONCLUSIONS: There are a vast number of HRQOL issues associated with cancer cachexia as identified from patients' own words. The model generated from these issues indicates that relationships, coping and knowledge of the condition are important components of new psychosocial interventions.


Subject(s)
Cachexia/psychology , Neoplasms/psychology , Quality of Life , Cachexia/etiology , Feeding and Eating Disorders/etiology , Humans , Neoplasms/complications , Qualitative Research
13.
Patient Prefer Adherence ; 9: 1043-51, 2015.
Article in English | MEDLINE | ID: mdl-26229451

ABSTRACT

BACKGROUND: Current American Cancer Society recommendations for colon cancer screening include optical colonoscopy every 10 years or computed tomography colonography (CTC) every 5 years. Bowel preparation (BP) is currently required for both screening modalities. PURPOSE: To compare ACRIN 6664: the National CT Colonography Trial (NCTCT) participant experiences with CTC and optical colonoscopy (OC), procedure preference, and willingness to return for each procedure. MATERIALS AND METHODS: Participants from fifteen NCTCT sites, who underwent CTC followed by OC under sedation, were invited to complete questionnaires 2 weeks postexam, asking about procedure preference, physical discomfort, and embarrassment experienced and whether that discomfort and embarrassment was better or worse than expected during BP, CTC, and OC, as well as willingness to return for repeat CTC and OC at different time intervals. RESULTS: A total of 2,310 of 2,600 patients (89%) returned their questionnaires. Of patients reporting a preference, 1,058 (46.6%) preferred CTC, 569 (25.0%) preferred OC, and 626 (27.6%) reported no preference. Participant-reported discomfort worse than expected differed significantly between CTC (32.9%) and OC (5.0%) (P<0.001). About 79.3% were willing to be screened again with CTC in 5 years, and 96.6% with OC in 10 years. Discomfort and embarrassment worse than expected with OC were associated with increased intention to adhere with CTC in the future. Conversely, embarrassment experienced during CTC and discomfort worse than expected on CTC were associated with increased intention to adhere with OC in the future. CONCLUSION: While a larger proportion of participants indicated that they preferred CTC to OC, willingness to undergo repeat CTC compared to OC was limited by unanticipated exam discomfort and embarrassment and CTC's shorter screening interval.

14.
Cell Death Differ ; 22(12): 1985-94, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25909884

ABSTRACT

Liver cancer is a major health-care concern and its oncogenic mechanisms are still largely unclear. Persistent hepatocyte cell death is a common feature among various chronic liver diseases, the blocking of which presents as logical treatment. Therefore, we aimed at investigating tumor development in mice with hepatocyte-specific Bid depletion--a BH3-only Bcl-2 family member that amplifies apoptotic death signals. Hepatocyte-specific conditional Bid-knockout mice (Bid(Δhep)) were injected with 25 mg/kg diethylnitrosamine (DEN) at 14 days of age, and liver tumorigenesis was investigated 9 months later. Additionally, different models of acute liver injury were used including: acute high-dose DEN challenge, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and carbon tetrachloride (CCL4) injection. Bid(Δhep) mice developed significantly fewer tumors, showed smaller maximal and average tumor size and reduced tumor incidence. In the acute DEN model, 48 h post injection we observed a significant reduction in liver injury in Bid(Δhep) animals, assessed via serum transaminases and liver histopathology. Furthermore, TNF-α, IL-1ß, cJUN and IL-6 mRNA expression was reduced. These findings were accompanied by reduced compensatory hepatocyte proliferation in Bid(Δhep) mice when compared with controls by immunohistochemistry for Ki67 and proliferating cell nuclear antigen 48 h after DEN injection. In the acute CCL4 model, Bid(Δhep) mice displayed reductions in liver injury and inflammation when compared with controls. No differences in liver injury and serum bilirubin levels were detected in Bid(Δhep) and Bid(flo/flo) mice fed with DDC, which induces bile duct injury and a ductular reaction. Our study demonstrates that in DEN-induced hepatocellular carcinoma, the inhibition of hepatocyte death pathways through Bid deletion protects animals from tumorigenesis. These results suggest that reducing hepatocyte cell death, liver inflammation and compensatory proliferation has a stronger beneficial effect than the potential side effect of enhancing tumor cell survival.


Subject(s)
BH3 Interacting Domain Death Agonist Protein/metabolism , Inflammation , Liver Neoplasms/pathology , Animals , BH3 Interacting Domain Death Agonist Protein/genetics , Carbon Tetrachloride/toxicity , Cell Proliferation/drug effects , Cells, Cultured , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cyclin D1/genetics , Cyclin D1/metabolism , Diethylnitrosamine/toxicity , Disease Models, Animal , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Hydrogen Peroxide/toxicity , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Liver/enzymology , Liver/metabolism , Liver/pathology , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Pyridines/toxicity , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
15.
Pancreatology ; 15(2): 101-4, 2015.
Article in English | MEDLINE | ID: mdl-25683639

ABSTRACT

BACKGROUND: The recent development of two different severity classifications for acute pancreatitis has appropriately raised questions about which should be used. The aim of this paper is to review the two new severity classifications, outline their differences, review validation studies, and identify gaps in knowledge to suggest a way forward. METHODS: A literature review was performed to identify the purposes and differences between the classifications. Validation studies and those comparing the two different classifications were also reviewed. RESULTS: The Revised Atlanta Classification (RAC) and the Determinants Based Classification (DBC) both rely on assessment of local and systemic factors. The differences between the classifications provides opportunities for further research to improve the accuracy and utility of severity classification. This includes understanding how best to tailor severity classification to setting (e.g. secondary or tertiary hospital) and purpose (e.g. clinical management or research). A key difference is that the RAC does not consider infected pancreatic necrosis an indicator of severe disease. There is also the need to develop methods for the accurate non-invasive diagnosis of infected necrosis and evaluation of the characteristics of organ dysfunction in relation to severity and outcome. CONCLUSION: Further improvement in severity classification is possible and research priorities have been identified. For now, the decision as to which classification to use should be on the basis of setting, validity, accuracy, and ease of use.


Subject(s)
Pancreatitis/classification , Acute Disease , Humans , Pancreatitis/complications , Pancreatitis/pathology , Prognosis , Reproducibility of Results
17.
Ground Water ; 52 Suppl 1: 195-200, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24898169

ABSTRACT

We apply fluid-replacement logging in arsenic-contaminated regions of Bangladesh using a low-cost, down-well fluid conductivity logging tool to detect leaks in the cased section of wells. The fluid-conductivity tool is designed for the developing world: it is lightweight and easily transportable, operable by one person, and can be built for minimal cost. The fluid-replacement test identifies leaking casing by comparison of fluid conductivity logs collected before and after spiking the wellbore with a sodium chloride tracer. Here, we present results of fluid-replacement logging tests from both leaking and non-leaking casing from wells in Araihazar and Munshiganj, Bangladesh, and demonstrate that the low-cost tool produces measurements comparable to those obtained with a standard geophysical logging tool. Finally, we suggest well testing procedures and approaches for preventing casing leaks in Bangladesh and other developing countries.


Subject(s)
Arsenic/analysis , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Water Supply/analysis , Water Wells/analysis , Bangladesh , Water Movements
18.
Diabetologia ; 56(7): 1629-37, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23604553

ABSTRACT

AIMS/HYPOTHESIS: The NAD(+)-dependent protein deacetylase sirtuin (SIRT)1 is thought to be a key regulator of skeletal muscle metabolism. However, its precise role in the regulation of insulin sensitivity is unclear. Accordingly, we sought to determine the effect of skeletal muscle-specific overexpression of SIRT1 on skeletal muscle insulin sensitivity and whole-body energy metabolism. METHODS: At 10 weeks of age, mice with muscle-specific overexpression of SIRT1 and their wild-type littermates were fed a standard diet with free access to chow or an energy-restricted (60% of standard) diet for 20 days. Energy expenditure and body composition were measured by indirect calorimetry and magnetic resonance imaging, respectively. Skeletal muscle insulin-stimulated glucose uptake was measured ex vivo in soleus and extensor digitorum longus muscles using a 2-deoxyglucose uptake technique with a physiological insulin concentration of 360 pmol/l (60 µU/ml). RESULTS: Sirt1 mRNA and SIRT1 protein levels were increased by approximately 100- and 150-fold, respectively, in skeletal muscle of mice with SIRT1 overexpression compared with wild-type mice. Despite this large-scale overexpression of SIRT1, body composition, whole-body energy expenditure, substrate oxidation and voluntary activity were comparable between genotypes. Similarly, skeletal muscle basal and insulin-stimulated glucose uptake were unaltered with SIRT1 overexpression. Finally, while 20 days of energy restriction enhanced insulin-stimulated glucose uptake in skeletal muscles of wild-type mice, no additional effect of SIRT1 overexpression was observed. CONCLUSIONS/INTERPRETATION: These results demonstrate that upregulation of SIRT1 activity in skeletal muscle does not affect whole-body energy expenditure or enhance skeletal muscle insulin sensitivity in young mice on a standard diet with free access to chow or in young mice on energy-restricted diets.


Subject(s)
Energy Metabolism/physiology , Insulin Resistance/physiology , Muscle, Skeletal/metabolism , Sirtuin 1/metabolism , Animals , Body Composition/genetics , Body Composition/physiology , Electrophoresis, Polyacrylamide Gel , Genotype , Mice , Reverse Transcriptase Polymerase Chain Reaction , Sirtuin 1/genetics
19.
Zoonoses Public Health ; 60(5): 327-35, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22978260

ABSTRACT

The first case of pandemic H1N1 influenza (pH1N1) virus in feral swine in the United States was identified in Texas through the United States Department of Agriculture (USDA) Wildlife Services' surveillance program. Two samples were identified as pandemic influenza by reverse transcriptase quantitative PCR (RT-qPCR). Full-genome Sanger sequencing of all eight influenza segments was performed. In addition, Illumina deep sequencing of the original diagnostic samples and their respective virus isolation cultures were performed to assess the feasibility of using an unbiased whole-genome linear target amplification method and multiple sample sequencing in a single Illumina GAIIx lane. Identical sequences were obtained using both techniques. Phylogenetic analysis indicated that all gene segments belonged to the pH1N1 (2009) lineage. In conclusion, we have identified the first pH1N1 isolate in feral swine in the United States and have demonstrated the use of an easy unbiased linear amplification method for deep sequencing of multiple samples.


Subject(s)
Animals, Wild , Influenza A Virus, H1N1 Subtype , Influenza, Human/virology , Orthomyxoviridae Infections/veterinary , Pandemics , Swine Diseases/virology , Animals , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/epidemiology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Swine , Swine Diseases/epidemiology , United States/epidemiology
20.
Thorac Surg Clin ; 22(4): 457-70, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23084610

ABSTRACT

There is mounting recognition that, to aid surgical decision making, treatment efficacy needs to be measured in a variety of ways, with health-related quality of life now widely regarded as an important outcome in pulmonary surgical populations. The aim of this review is to provide a comprehensive overview of the key issues to consider if an investigator wishes to incorporate health-related quality of life assessment into trials and studies of pulmonary surgery, drawing on recent studies of lung cancer surgery as an example.


Subject(s)
Health Status , Lung Neoplasms/surgery , Quality of Life , Age Factors , Humans , Outcome Assessment, Health Care , Postoperative Complications/psychology , Psychometrics
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