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INTRODUCTION: Domestic violence (DV) is common in the Australian community so it is likely that there will be medical students who are affected personally by DV. Some of these students may find DV training confronting or even re-traumatising. A trauma-informed medical education (TIME) framework utilising trauma-informed care principles may minimise this risk to students. We aimed to explore educators' perceptions of student well-being in Australian medical school DV training. METHOD: This descriptive qualitative study interviewed 13 educators with experience teaching DV in Australian medical schools using an interpretivist methodology and a TIME framework. Interview data was thematically analysed to identify themes. RESULTS: Four key themes included (1) educators thrown in at the deep end; (2) keeping students emotionally safe; (3) a trauma-informed learning environment and; (4) challenges of student DV disclosures. Few of the participants had received training in DV. Educators used methods such as trigger warnings and ground rules to improve student's emotional safety. Experienced educators dealt with disclosures of DV by students which led to role confusion. DISCUSSION: There is a need for increased training of medical educators that includes awareness and implementation of TIME principles when training medical students in DV as well as increased supports and resources for educators.
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Violencia Doméstica , Estudiantes de Medicina , Humanos , Australia , Investigación Cualitativa , Violencia Doméstica/psicología , CurriculumRESUMEN
Hydrologic monitoring began on two headwater streams (<1 km2) on the University of Kentucky's Robinson Forest in 1971. We evaluated stream-water (1974-2013) and bulk-deposition (wet + dust) (1984-2013) chemistry in the context of regional wet-deposition patterns that showed decreases in both sulfate and nitrate concentrations as well as proximal surface-mine expansion. Decadal time steps (1974-83, 1984-93, 1994-2003, 2004-2013) were used to quantify change. Comparison of the first two decades showed similarly decreased sulfate (minimum flow-adjusted annual-mean concentration of ≈13.5 mg/L in 1982 to 8.8 mg/L in 1992) and increased pH (6.6-6.8) in both streams, reflecting contemporaneous changes in both bulk and wet deposition. In contrast, concentrations of nitrate (0.14 to >0.25 mg/L) and base cations increased between these two decades, coinciding with expansion of surface mining between 1985 and 1995. In 2004, stream-water pH (6.7 in 2004), sulfate (9.2 mg/L), and nitrate (>0.11 mg/L) were similar to 1982, despite wet-deposition concentrations being lower. Base-cation concentrations were higher in the stream adjacent to ongoing surface mining relative to the stream situated near the middle of the experimental forest. However, pH decreased to approximately 5.7 by 2013 for both streams, which, combined with a shift in dominant cations from calcium to magnesium and potassium, indicates that the soil-buffering capacity of this landscape has been exceeded. Ratios of bulk deposition and stream-water concentrations indicate enrichment of sulfate (1.7-25.2) and cations (0.5-64.8), but not nitrogen (0.1-5.6), indicating that the Forest is not nitrogen saturated and that ongoing changes in water-quality are sulfate driven. When concentrations were adjusted to account for changes in streamflow (climate) over the 4 decades, external influences (land management/regulation) explained most change. The amount and direction of change differed among constituents, both between consecutive decades and between the first and last decades, reflecting the influence of localized surface mining even as regional wet deposition continued to improve due to the Clean Air Act. The implication is that localized stressors have the potential to out-pace the benefits of national environmental policies for communities that depend on local water-resources in similar environments.
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Ríos , Agua , Nitratos/análisis , Bosques , Compuestos Orgánicos , Región de los Apalaches , Sulfatos/análisis , Cationes , Monitoreo del AmbienteRESUMEN
OBJECTIVE: Previous studies examined the use of video-based diagnosis and the predictive value of videos for differentiation of epileptic seizures (ES) from paroxysmal nonepileptic events (PNEE) in the adult population. However, there are no such published studies strictly on the pediatric population. Using video-EEG diagnosis as a gold standard, we aimed to determine the diagnostic predictive value of videos of habitual events with or without additional clinical data in differentiating the PNEE from ES in children. METHODS: Consecutive admissions to our epilepsy monitoring unit between June 2020 and December 2020 were analyzed for events of interest. Four child neurologists blinded to the patient's diagnosis formulated a diagnostic impression based upon the review of the video alone and again after having access to basic clinical information, in addition to the video. Features of the video which helped to make a diagnosis were identified by the reviewers as a part of a survey. RESULTS: A total of 54 patients were included (ES n = 24, PNEE n = 30). Diagnostic accuracy was calculated for each reviewer and combined across all the ratings. Diagnostic accuracy by video alone was 74.5% (sensitivity 80.8%, specificity 66.7%). Providing reviewers with basic clinical information in addition to the videos significantly improved diagnostic accuracy compared to viewing the videos alone. Inter-rater reliability between four reviewers based on the video alone showed moderate agreement (κ = 0.51) and unchanged when additional clinical data were presented (κ = 0.51). The ES group was significantly more likely to demonstrate changes in facial expression, generalized stiffening, repetitive eye blinks, and eye deviation when compared with the PNEE group, which was more likely to display bilateral myoclonic jerking. CONCLUSIONS: Video review of habitual events by Child Neurologists may be helpful in reliably distinguishing ES from PNEE in children, even without included clinical information.
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Epilepsia , Adulto , Niño , Electroencefalografía , Humanos , Reproducibilidad de los Resultados , Convulsiones , Grabación en VideoRESUMEN
Etoposide is a widely-used anticancer agent that targets human type II topoisomerases. Evidence suggests that metabolism of etoposide in myeloid progenitor cells is associated with translocations involved in leukemia development. Previous studies suggest halogenation at the C-2' position of etoposide reduces metabolism. Halogens were introduced into the C-2' position by electrophilic aromatic halogenation onto etoposide (ETOP, 1), podophyllotoxin (PPT, 2), and 4-dimethylepipodophyllotoxin (DMEP, 3), and to bridge the gap of knowledge regarding the activity of these metabolically stable analogs. Five halogenated analogs (6-10) were synthesized. Analogs 8-10 displayed variable ability to inhibit DNA relaxation. Analog 9 was the only analog to show concentration-dependent enhancement of Top2-mediated DNA cleavage. Dose response assay results indicated that 8 and 10 were most effective at decreasing the viability of HCT-116 and A549 cancer cell lines in culture. Flow cytometry with 8 and 10 in HCT-116 cells provide evidence of sub-G1 cell populations indicative of apoptosis. Taken together, these results indicate C-2' halogenation of etoposide and its precursors, although metabolically stable, decreases overall activity relative to etoposide.
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Antineoplásicos/farmacología , ADN-Topoisomerasas de Tipo II/metabolismo , Etopósido/farmacología , Podofilotoxina/farmacología , Inhibidores de Topoisomerasa II/farmacología , Células A549 , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , División del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Etopósido/síntesis química , Etopósido/química , Células HCT116 , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Plásmidos/efectos de los fármacos , Podofilotoxina/síntesis química , Podofilotoxina/química , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/químicaRESUMEN
Background: While atopic conditions are associated with increased risk of mental health problems, the evidence that a range of allergic conditions are associated with psychological distress in young people is less clear.Methods: We recruited a longitudinal birth cohort study of 620 children with a family history of allergic disease. At the 18-year follow up, atopic sensitization was determined by skin prick testing. Surveys were used to determine psychological distress (Kessler 6), quality of life (SF12), respiratory symptoms and management, presence of current eczema and hay fever. Regression models were used to identify predictors of psychological distress and quality of life, while controlling for potential confounders.Results: Prevalence of serious psychological distress was quite low (n = 22, 5.3%), and there were no associations between psychological distress and current atopic sensitization, symptoms of hay fever, eczema or asthma. Smoking status and lower level of maternal education were associated with lower physical quality of life (SF12 PCS subscale). Psychological distress total score, lower maternal education, smoking, female sex, and current eczema were associated with worse mental quality of life (SF12 MCS subscale).Conclusion: We found relatively low levels of psychological distress in this cohort of young adults, despite a high prevalence of allergic diseases. Positive social factors may serve to buffer psychological distress amongst the cohort accounting for the low prevalence of serious psychological distress observed.
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Asma/psicología , Hipersensibilidad Inmediata/psicología , Distrés Psicológico , Calidad de Vida , Adolescente , Asma/complicaciones , Asma/diagnóstico , Asma/inmunología , Australia/epidemiología , Niño , Estudios de Cohortes , Estudios Transversales , Escolaridad , Femenino , Humanos , Hipersensibilidad Inmediata/complicaciones , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/inmunología , Estudios Longitudinales , Masculino , Prevalencia , Factores de Riesgo , Autoinforme , Factores Sexuales , Fumar/epidemiologíaRESUMEN
Expression of E7 proteins encoded by carcinogenic, high-risk human papillomaviruses (HPVs) triggers increased expression of the histone H3 lysine 27 demethylase KDM6A. KDM6A expression is necessary for survival of high-risk HPV E7 expressing cells, including several cervical cancer lines. Here we show that increased KDM6A in response to high-risk HPV E7 expression causes epigenetic de-repression of the cell cycle and DNA replication inhibitor p21CIP1, and p21CIP1 expression is necessary for survival of high-risk HPV E7 expressing cells. The requirement for KDM6A and p21CIP1 expression for survival of high-risk HPV E7 expressing cells is based on p21CIP1's ability to inhibit DNA replication through PCNA binding. We show that ectopic expression of cellular replication factors can rescue the loss of cell viability in response to p21CIP1 and KDM6A depletion. Moreover, we discovered that nucleoside supplementation will override the loss of cell viability in response to p21CIP1 depletion, suggesting that p21CIP1 depletion causes lethal replication stress. This model is further supported by increased double strand DNA breaks upon KDM6A or p21CIP1 depletion and DNA combing experiments that show aberrant re-replication upon KDM6A or p21CIP1 depletion in high-risk HPV E7 expressing cells. Therefore, KDM6A and p21CIP1 expression are essential to curb E7 induced replication stress to levels that do not markedly interfere with cell viability.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Replicación del ADN/genética , Histona Demetilasas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas E7 de Papillomavirus/genética , Neoplasias del Cuello Uterino/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Queratinocitos/metabolismo , Neoplasias del Cuello Uterino/genéticaRESUMEN
BACKGROUND: Smoking prevalence remains inequitably high for lower SES (socioeconomic status) populations. The psychosocial interactive model of resilience theorises that resilience might be 'switched on' in order to support and/or maintain smoking cessation for these populations. This study aimed to develop a Resilience Intervention for Smoking Cessation (RISC) through reviewing the extant literature around efficacious interventions for smoking cessation. Deliberative democracy principles were then used to understand lay perspectives regarding this potential smoking cessation program. METHODS: Public health databases were searched to find efficacious psycho-social resilience interventions in the peer-reviewed literature for smoking cessation amongst lower SES populations. Potential components for RISC were selected based on evidence within the literature for their effectiveness. We then employed the Nominal Group Technique (NGT) to create discussion and consensus on the most socially appropriate and feasible components from the perspective of smokers from low SES areas. The NGT included 16 people from a lower SES population in southern metropolitan Adelaide who indicated they were seriously contemplating quitting smoking or had recently quit. Data were collected from multiple Likert ratings and rankings of the interventions during the NGT workshop and analysed descriptively. The Wilcoxon signed-ranked test was used where appropriate. Qualitative data were collected from participant reflections and group discussion, and analysed thematically. RESULTS: Six smoking cessation interventions, likely to enhance resilience, were selected as potential constituents for RISC: mindfulness training; setting realistic goals; support groups; smoke free environments; mobile phone apps; and motivational interviewing. Consensus indicated that mindfulness training and setting realistic goals were the most acceptable resilience enhancing interventions, based on perceived usefulness and feasibility. CONCLUSIONS: This research applied principles from deliberative democracy in order to illuminate lay knowledge regarding an appropriate and acceptable smoking cessation resilience program for a lower SES population. This process of collaborative and complex knowledge-generation is critically important to confront inequities as an ongoing challenge in public health, such as smoking cessation for disadvantaged groups. Further research should involve development and trial of this resilience program.
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Consenso , Cese del Hábito de Fumar/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pobreza , Resiliencia Psicológica , Fumadores/psicología , Fumadores/estadística & datos numéricos , Cese del Hábito de Fumar/psicologíaRESUMEN
BACKGROUND: The neurobiology of persistent pain shares common underlying psychobiology with that of traumatic stress. Modern treatments for traumatic stress often involve bottom-up sensorimotor retraining/exposure therapies, where breath, movement, balance and mindfulness, are used to target underlying psychobiology. Vigorous exercise, in particular Bikram yoga, combines many of these sensorimotor/exposure therapeutic features. However, there is very little research investigating the feasibility and efficacy of such treatments for targeting the underlying psychobiology of persistent pain. METHODS: This study was a randomized controlled trail (RCT) comparing the efficacy of Bikram yoga versus high intensity interval training (HIIT), for improving persistent pain in women aged 20 to 50 years. The participants were 1:1 randomized to attend their assigned intervention, 3 times per week, for 8 weeks. The primary outcome measure was the Brief Pain Inventory (BPI) and further pain related biopsychosocial secondary outcomes, including SF-36 Medical Outcomes and heart rate variability (HRV), were also explored. Data was collected pre (t0) and post (t1) intervention via an online questionnaire and physiological testing. RESULTS: A total of 34 women were recruited from the community. Analyses using ANCOVA demonstrated no significant difference in BPI (severity plus interference) scores between the Bikram yoga (n = 17) and the HIIT (n = 15). Women in the Bikram yoga group demonstrated significantly improved SF-36 subscale physical functioning: [ANCOVA: F(1, 29) = 6.17, p = .019, partial eta-squared effect size (ηp2) = .175 and mental health: F(1, 29) = 9.09, p = .005, ηp2 = .239; and increased heart rate variability (SDNN): F(1, 29) = 5.12, p = .013, ηp2 = .150, scores compared to the HIIT group. Across both groups, pain was shown to decrease, no injuries were experienced and retention rates were 94% for Bikram yoga and 75% for HIIT . CONCLUSIONS: Bikram yoga does not appear a superior exercise compared to HIIT for persistent pain. However, imporvements in quality of life measures and indicator of better health were seen in the Bikram yoga group. The outcomes of the present study suggest vigorous exercise interventions in persistent pain cohorts are feasible. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12617001507370 , 26/10/2017).
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Dolor Crónico , Terapia por Ejercicio , Entrenamiento de Intervalos de Alta Intensidad , Heridas y Lesiones/complicaciones , Yoga , Adulto , Dolor Crónico/etiología , Dolor Crónico/terapia , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Adulto JovenRESUMEN
BACKGROUND: There is a growing evidence that resilience to stress can promote nonsmoking. However, few studies have undertaken quantitative research to investigate whether resilience, generated by internal and external factors, moderates the impact of stress on the likelihood of smoking. OBJECTIVE: This study aims to help fill this knowledge gap in relation to smokers and ex-smokers, and those people who have never smoked. METHODS: A large online cross-sectional survey was administered in Australia (2015-2016) to collect data on demographic variables, levels of internal and external resilience, and stress from current and past smokers (n = 400) and those who have never-smoked (n = 921). Logistic regressions were employed to test our hypotheses. RESULTS: Most participants were female (82%) and ranged between 18 and 77 years. Higher levels of reported perceived stress and stress-related variables did significantly predict smoking. The combined impact of internal and external resilience factors predicted never-smoking and lessened the relationship between perceived stress and stress-related variables, and the likelihood of smoking. CONCLUSION: These results are important because they suggest that the social environment should be developed to augment social support and internal properties such as developing "a strong sense of purpose in life" to encourage people not to commence smoking, rather than focus on smoking cessation.
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Resiliencia Psicológica , Fumadores/psicología , Cese del Hábito de Fumar/psicología , Fumar/psicología , Apoyo Social , Estrés Psicológico/psicología , Adolescente , Adulto , Anciano , Australia , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Cervical cancer is a major cause of death in females worldwide. While survival rates have historically improved, there remains a continuous need to identify novel molecules that are effective against this disease. Here, we show that enoxacin, a drug most commonly used to treat a broad array of bacterial infections, is able to inhibit growth of the cervical cancer cells. Furthermore, our data show that epigallocatechin gallate (EGCG), a plant bioactive compound abundant in green tea, and known for its antioxidant effects, similarly functions as an antiproliferative agent. Most importantly, we provide evidence that EGCG functions synergistically against cancer cell proliferation in combined treatment with enoxacin. These data collectively suggest that enoxacin and EGCG may be useful treatment options for cases of cervical cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Catequina/agonistas , Catequina/análogos & derivados , Catequina/farmacología , Enoxacino/agonistas , Enoxacino/farmacología , Femenino , Células HeLa , Humanos , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
A phylogenetic tree at the species level is still far off for highly diverse insect orders, including the Coleoptera, but the taxonomic breadth of public sequence databases is growing. In addition, new types of data may contribute to increasing taxon coverage, such as metagenomic shotgun sequencing for assembly of mitogenomes from bulk specimen samples. The current study explores the application of these techniques for large-scale efforts to build the tree of Coleoptera. We used shotgun data from 17 different ecological and taxonomic datasets (5 unpublished) to assemble a total of 1942 mitogenome contigs of >3000â¯bp. These sequences were combined into a single dataset together with all mitochondrial data available at GenBank, in addition to nuclear markers widely used in molecular phylogenetics. The resulting matrix of nearly 16,000 species with two or more loci produced trees (RAxML) showing overall congruence with the Linnaean taxonomy at hierarchical levels from suborders to genera. We tested the role of full-length mitogenomes in stabilizing the tree from GenBank data, as mitogenomes might link terminals with non-overlapping gene representation. However, the mitogenome data were only partly useful in this respect, presumably because of the purely automated approach to assembly and gene delimitation, but improvements in future may be possible by using multiple assemblers and manual curation. In conclusion, the combination of data mining and metagenomic sequencing of bulk samples provided the largest phylogenetic tree of Coleoptera to date, which represents a summary of existing phylogenetic knowledge and a defensible tree of great utility, in particular for studies at the intra-familial level, despite some shortcomings for resolving basal nodes.
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Escarabajos/genética , Metagenómica , Mitocondrias/genética , Filogenia , Algoritmos , Animales , Secuencia de Bases , Escarabajos/clasificación , Bases de Datos GenéticasRESUMEN
OBJECTIVES: Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenotyped cohort of UK children and (b) to perform a systematic review and meta-analysis. METHODS: We recruited 149 children from seven UK centres using a retrospective cohort study design. All participants were clinically phenotyped carefully. Genotyping was performed for one ACYP2 (rs1872328), three TPMT (rs12201199, rs1142345 and rs1800460) and two COMT (rs4646316 and rs9332377) variants. RESULTS: For CTCAE grading, hearing loss was present in 91/120 (75.8%; worst ear) and 79/120 (65.8%; better ear). Using Chang grading, hearing loss was diagnosed in 85/119 (71.4%; worst ear) versus 75/119 (63.0%; better ear). No TPMT or COMT single-nucleotide polymorphisms (SNPs) were associated with ototoxicity. ACYP2 SNP rs1872328 was associated with ototoxicity (P=0.027; worst ear). Meta-analysis of our data with that reported in previous studies showed the pooled odds ratio (OR) to be statistically significant for both the COMT SNP rs4646316 (OR: 1.50; 95% confidence interval: 1.15-1.95) and the ACYP2 SNP rs1872328 (OR: 5.91; 95% confidence interval: 1.51-23.16). CONCLUSION: We showed an association between the ACYP2 polymorphism and cisplatin-induced ototoxicity, but not with the TPMT and COMT. A meta-analysis was statistically significant for both the COMT rs4646316 and the ACYP2 rs1872328 SNPs. Grading the hearing of children with asymmetric hearing loss requires additional clarification.
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Ácido Anhídrido Hidrolasas/genética , Antineoplásicos/efectos adversos , Catecol O-Metiltransferasa/genética , Cisplatino/efectos adversos , Pérdida Auditiva/diagnóstico , Metiltransferasas/genética , Polimorfismo de Nucleótido Simple , Adolescente , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/genética , Humanos , Lactante , Masculino , Oportunidad Relativa , Estudios Retrospectivos , Reino UnidoRESUMEN
Glycosylation often plays a key role in the safety and efficacy of therapeutic proteins to patients, thus underlying the need for consistent control of this important post-translational modification during biologics production. In this study, we profiled the site-specific evolution of N-glycans on a CTLA4-Fc-fusion protein, from the intracellular secretory pathway to the conditioned medium (CM) in fed-batch cell culture. For this, we developed an approach that combined sub-cellular fractionation with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. The study revealed that there was a significant amount of heterogeneity in the glycans displayed amongst the three distinct N-glycosylation sites. Furthermore, 54-60% of the intracellular protein was characterized by Man8 and Man9 glycans on day 10, when the cell density peaks, indicative of a significant bottleneck between the endoplasmic reticulum (ER) and the cis-Golgi. At longer culture duration, the accumulation of intracellular protein with bi-antennary-fucosylated GlcNAc-terminated residues identified the formation of another bottleneck in the medial and trans-Golgi compartments, which subsequently led to a decrease in sialylated species in the secreted protein. Glucose deprivation caused a reduction in the Man8 and Man9 glycans in favor of Man5 glycans and bi-antennary-fucosylated GlcNAc-terminated residues in the organellar pool of the Fc-fusion protein. However, transient deprivation of glucose did not lead to major differences in the glycan profile of proteins secreted into the CM. The approach developed here allows us to probe the secretory pathway and sheds light on the site-specific intracellular processing of glycans during fed-batch cell culture, thus serving as an initial step towards their rational control. Biotechnol. Bioeng. 2017;114: 1550-1560. © 2017 Wiley Periodicals, Inc.
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Antígeno CTLA-4/metabolismo , Microambiente Celular/fisiología , Espacio Extracelular/fisiología , Fragmentos Fc de Inmunoglobulinas/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Proteínas Recombinantes de Fusión/metabolismo , Vías Secretoras/fisiología , Animales , Células CHO , Cromatografía Liquida/métodos , Cricetulus , Glicosilación , Espectrometría de Masas/métodosRESUMEN
Coagulation factor II (prothrombin; FII) is the pre-proteolyzed precursor to thrombin in the coagulation cascade. It has 10 sites of gamma-carboxylation, which are required for its bioactivity, and is N-glycosylated at three of four putative sites. Production of recombinant human FII (rhFII) using a platform fed-batch process designed for monoclonal antibody production resulted in low levels of gamma-carboxylation and sialylation. There have not been any prior reports of successful process development and clinical manufacture of rhFII with optimal, consistent gamma-carboxylation and sialylation. In order to develop such a fed-batch process, various process parameters were evaluated to determine their impact on product quality. Process temperature and temperature shift timing were important for both sialic acid level and gamma-carboxyglutamate (Gla) level. In addition, vitamin K concentration and the type of surfactant used for preparation of vitamin K stock solution were also important for gamma carboxylation. A fed-batch study performed with various medium additives known to be involved in the N-glycosylation pathway, such as N-acetyl-d-mannosamine (ManNAc), galactose (Gal), dexamethasone, and manganese sulfate, increased the level of sialylation and enabled the elucidation of some potential bottlenecks in the sialylation pathway. The optimized process based on these studies yielded a reduction in the level of missing Gla by 0.4 moles per mole of rhFII in cell culture and a nearly threefold increase in sialic acid level. The process was successfully implemented at the 2000 L scale where a high Gla level and sialylation levels were achieved in all GMP lots. Biotechnol. Bioeng. 2017;114: 1991-2000. © 2017 Wiley Periodicals, Inc.
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Modelos Biológicos , Ácido N-Acetilneuramínico/metabolismo , Ingeniería de Proteínas/métodos , Protrombina/biosíntesis , Protrombina/genética , Proteínas Recombinantes/biosíntesis , Animales , Células CHO , Metabolismo de los Hidratos de Carbono/fisiología , Simulación por Computador , Cricetulus , Humanos , Análisis de Flujos Metabólicos , Redes y Vías Metabólicas/fisiología , Proteínas Recombinantes/genéticaRESUMEN
We evaluated whether a chronic obstructive pulmonary disease (COPD) assessment test (CAT) with adjusted weights for the CAT items could better predict future respiratory-related hospitalizations than the original CAT. Two focus groups (respiratory nurses and physicians) generated two adjusted CAT algorithms. Two multivariate logistic regression models for infrequent (≤1/year) versus frequent (>1/year) future respiratory-related hospitalizations were defined: one with the adjusted CAT score that correlated best with future hospitalizations and one with the original CAT score. Patient characteristics related to future hospitalizations ( p ≤ 0.2) were also entered. Eighty-two COPD patients were included. The CAT algorithm derived from the nurse focus group was a borderline significant predictor of hospitalization risk (odds ratio (OR): 1.07; 95% confidence interval (CI): 1.00-1.14; p = 0.050) in a model that also included hospitalization frequency in the previous year (OR: 3.98; 95% CI: 1.30-12.16; p = 0.016) and anticholinergic risk score (OR: 3.08; 95% CI: 0.87-10.89; p = 0.081). Presence of ischemic heart disease and/or heart failure appeared 'protective' (OR: 0.17; 95% CI: 0.05-0.62; p = 0.007). The original CAT score was not significantly associated with hospitalization risk. In conclusion, as a predictor of respiratory-related hospitalizations, an adjusted CAT score was marginally significant (although the original CAT score was not). 'Previous respiratory-related hospitalizations' was the strongest factor in this equation.
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Hospitalización/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Algoritmos , Antagonistas Colinérgicos/uso terapéutico , Disnea/etiología , Ejercicio Físico , Tolerancia al Ejercicio , Femenino , Grupos Focales , Volumen Espiratorio Forzado , Insuficiencia Cardíaca/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Isquemia Miocárdica/epidemiología , Enfermeras y Enfermeros , Oportunidad Relativa , Valor Predictivo de las Pruebas , Factores Protectores , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Neumólogos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: For research to be ethically acceptable, the potential benefits must justify any risks involved for participants. Dissemination of research findings through publication is one way of creating benefit, but not all researchers intend to publish their research. Other factors, such as lack of size or representativeness, generalisability or innovativeness, or negative findings mean the research is unlikely to be published in a peer-reviewed medical journal. OBJECTIVE: This paper discusses ethical considerations in research where peer-reviewed publication is not intended or unlikely. DISCUSSION: Proposing research that is not intended or unlikely to be published in a peer-reviewed journal does not preclude it from being considered ethical. Additional benefits of such projects may include professional development of investigators, pilot data collection leading to more definitive studies, or developing collaborations with research users that increase relevance and improve utility of findings.
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Ética en Investigación , Edición/estadística & datos numéricos , Proyectos de Investigación/normas , Humanos , Revisión de la Investigación por Pares/tendenciasRESUMEN
BACKGROUND: How patients are selected and subsequently invited to take part in research has important implications for gaining informed, voluntary consent. OBJECTIVE: This article identifies and discusses common ethical issues that are faced by researchers when recruiting patients from primary care settings. DISCUSSION: Recruiting primary care patients for research studies should be guided by the core ethical values of merit and integrity, respect, justice and beneficence. Issues of patient privacy and risk of coercion are major concerns when selecting and recruiting primary care patients, but the ethical issues will depend on the type of research and the potential risks to participants. The National Statement on Ethical Conduct in Human Research, and Australian privacy laws and principles, should be reviewed to ensure recruitment meets contemporary ethical standards prior to submitting a study protocol for ethical review.
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Investigación Biomédica/ética , Medicina General/ética , Selección de Paciente/ética , Atención Primaria de Salud/ética , Australia , Ética Médica , Humanos , Consentimiento Informado , PrivacidadRESUMEN
This study was undertaken to provide a snapshot of the academic primary health-care workforce in Australia and to provide some insight into research capacity in academic primary health care following changes to funding for this sector. A convenience sample of individuals self-identifying as working within academic primary health care (n=405) completed an anonymous online survey. Respondents were identified from several academic primary health-care mailing lists. The survey explored workforce demographics, clarity of career pathways, career trajectories and enablers/barriers to 'getting in' and 'getting on'. A mix of early career (41%), mid-career (25%) and senior academics (35%) responded. Early career academics tended to be female and younger than mid-career and senior academics, who tended to be male and working in 'balanced' (teaching and research) roles and listing medicine as their disciplinary background. Almost three-quarters (74%) indicated career pathways were either 'completely' or 'somewhat unclear', irrespective of gender and disciplinary backgrounds. Just over half (51%) had a permanent position. Males were more likely to have permanent positions, as were those with a medical background. Less than half (43%) reported having a mentor, and of the 57% without a mentor, more than two-thirds (69%) would like one. These results suggest a lack of clarity in career paths, uncertainty in employment and a large number of temporary (contract) or casual positions represent barriers to sustainable careers in academic primary health care, especially for women who are from non-medicine backgrounds. Professional development or a mentoring program for primary health-care academics was desired and may address some of the issues identified by survey respondents.
Asunto(s)
Selección de Profesión , Atención Primaria de Salud , Adulto , Anciano , Anciano de 80 o más Años , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Recursos HumanosRESUMEN
A scoping review was conducted to determine the size and nature of the evidence describing associations between social support and networks on health, management and clinical outcomes amongst patients with COPD. Searches of PubMed, PsychInfo and CINAHL were undertaken for the period 1966-December 2013. A descriptive synthesis of the main findings was undertaken to demonstrate where there is current evidence for associations between social support, networks and health outcomes, and where further research is needed. The search yielded 318 papers of which 287 were excluded after applying selection criteria. Two areas emerged in which there was consistent evidence of benefit of social support; namely mental health and self-efficacy. There was inconsistent evidence for a relationship between perceived social support and quality of life, physical functioning and self-rated health. Hospital readmission was not associated with level of perceived social support. Only a small number of studies (3 articles) have reported on the social network of individuals with COPD. There remains a need to identify the factors that promote and enable social support. In particular, there is a need to further understand the characteristics of social networks within the broader social structural conditions in which COPD patients live and manage their illness.