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1.
Clin Immunol ; 264: 110260, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788885

RESUMO

Sjögren's disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39hi exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.


Assuntos
Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Aparelho Lacrimal , Camundongos Endogâmicos NOD , Síndrome de Sjogren , Animais , Síndrome de Sjogren/imunologia , Camundongos , Linfócitos T CD8-Positivos/imunologia , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/patologia , Interleucinas/imunologia , Interleucinas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Feminino , Transdução de Sinais/imunologia , Receptores de Interleucina/imunologia , Interleucina-27/metabolismo , Interleucina-27/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Apirase/imunologia , Apirase/metabolismo
2.
J Gen Virol ; 103(8)2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35972225

RESUMO

Bats have been implicated as the reservoir hosts of filoviruses in Africa, with serological evidence of filoviruses in various bat species identified in other countries. Here, serum samples from 190 bats, comprising 12 different species, collected in Australia were evaluated for filovirus antibodies. An in-house indirect microsphere assay to detect antibodies that cross-react with Ebola virus (Zaire ebolavirus; EBOV) nucleoprotein (NP) followed by an immunofluorescence assay (IFA) were used to confirm immunoreactivity to EBOV and Reston virus (Reston ebolavirus; RESTV). We found 27 of 102 Yinpterochiroptera and 19 of 88 Yangochiroptera samples were positive to EBOV NP in the microsphere assay. Further testing of these NP positive samples by IFA revealed nine bat sera that showed binding to ebolavirus-infected cells. This is the first report of filovirus-reactive antibodies detected in Australian bat species and suggests that novel filoviruses may be circulating in Australian bats.


Assuntos
Quirópteros , Ebolavirus , Doença pelo Vírus Ebola , Animais , Anticorpos Antivirais , Austrália , Doença pelo Vírus Ebola/veterinária , Nucleoproteínas
3.
Immunol Invest ; 51(6): 1612-1629, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34844506

RESUMO

The nonreceptor tyrosine kinase ITK is a key component of the T cell receptor (TCR) signaling pathway and is required for cytokine production by CD4+ T cells that have differentiated into Th2 cells. Structural and biochemical studies suggest that contacts between the SH2 and SH3 domains of ITK mediate intermolecular self-association, forming a structure that restrains ITK activity by interfering with interactions between ITK and other components of the TCR signaling pathway. Wild-type (WT) ITK and a panel of ITK mutants containing amino acid substitutions in the SH2 and SH3 domains were tested for self-association and for binding to the adaptor protein SLP76, a key ligand for the ITK SH2 domain. WT and ITK mutants were also expressed in Itk-deficient CD4+ T cells via retroviral-mediated gene delivery to analyze their ability to support TCR signaling and cytokine production by Th2 cells. Specific amino acid substitutions in the ITK SH2 or SH3 domains impaired self-association, with the greatest effects being seen when both intermolecular SH2-SH3 domain contacts were disrupted. Two of the SH2 domain substitutions tested reduced ITK self-association but had no effect on binding to SLP-76. When their function was analyzed in Th2 cells, ITK proteins with diminished self-association activity supported greater IL-4 production and calcium flux in response to TCR stimulation compared to WT ITK. Our findings indicate that intermolecular contacts between ITK molecules can restrain the amplitude of TCR signaling, suggesting ITK is a limiting factor for responses by CD4+ T cells.


Assuntos
Transdução de Sinais , Domínios de Homologia de src , Linfócitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Ligação Proteica , Receptores de Antígenos de Linfócitos T/genética , Células Th2
4.
BMC Med Educ ; 21(1): 246, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926426

RESUMO

BACKGROUND: Undergraduate medical education recognises that patient feedback is potentially valuable for student learning and development as a component of multi-source feedback. However greater exploration of how patient feedback perspectives differ to clinical educators is required for curriculum development and improving student feedback literacy. This study aimed to determine how two sources of feedback, patients and clinical tutors, compare on the same patient-centred, interpersonal criteria. METHODS: A patient feedback instrument designed for the undergraduate medical education setting was used to compare patients' feedback with clinical tutors' feedback following a student-patient consultation in the learning context. Assessments from 222 learning consultations involving 40 medical students were collected. Descriptive statistics for tutors and patients for each question were calculated and correlations between patient and tutor were explored using Spearman's rank-order correlation. Mixed effects ordered logistic regression was used to compare each question with an overall rating for tutor and patients in addition to comparing patient with tutor ratings. RESULTS: Clinical tutor and patient assessments had a weak but significant positive correlation in all areas except questions related to respect and concern. When making judgements compared with overall assessment, patients' ratings of respect, concern, communication and being understood in the consultation have a greater effect. After eliminating the effect of generally higher ratings by patients compared with tutors using comparative ordered logistic regression, patients rated students relatively less competent in areas of personal interaction. CONCLUSION: This study provides insight about patient feedback, which is required to continue improving the use and acceptability of this multisource feedback to students as a valuable component of their social learning environment. We have revealed the different perspective-specific judgement that patients bring to feedback. This finding contributes to building respect for patient feedback through greater understanding of the elements of consultations for which patients can discriminate performance.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Retroalimentação , Humanos , Aprendizagem Baseada em Problemas , Encaminhamento e Consulta , Ensino
5.
South Med J ; 113(1): 16-19, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31897493

RESUMO

OBJECTIVES: The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution. METHODS: A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed. RESULTS: Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages. CONCLUSIONS: Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.


Assuntos
Sarcoma Sinovial/mortalidade , Adulto , Fatores Etários , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sarcoma Sinovial/patologia , Taxa de Sobrevida
6.
AJR Am J Roentgenol ; 212(6): 1377-1384, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30917019

RESUMO

OBJECTIVE. The purpose of this study was to review the efficacy and durability of pain control and local tumor control using microwave ablation and cementoplasty in treating extraspinal osseous tumors. Painful osseous metastases are a common cause of cancer-related morbidity. Percutaneous thermal ablation presents an attractive minimally invasive option in this vulnerable patient group. MATERIALS AND METHODS. A retrospective review included 65 patients (35 men, 30 women) with 77 tumors who underwent image-guided microwave ablation and cementoplasty at a tertiary referral academic center over 18 months. Procedural efficacy was determined with a visual analog scale before the procedure and 24 hours, 2-4 weeks, and 20-24 weeks after the procedure. Locoregional control was assessed at follow-up cross-sectional imaging. RESULTS. The 77 tumors were in the following locations: ilium, 38; acetabulum on supraacetabular region, 23; femur, five; humerus, four; shoulder, four; sternum, three. The tumors were 15 multiple myelomas and metastases from cancers of the following organs: colon, nine; lung, 15; breast, 12; thyroid, seven; prostate, three; and kidney, four. Complete, successful ablation of all 77 tumors was achieved. Mean ablation time was 6 minutes 15 seconds (SD, 12 seconds), and mean energy used was 5.49 (SD, 2.97) kJ. The mean visual analog scale scores were 6.32 (SD, 1.94) before the procedure, 1.01 (SD, 1.24) at 24 hours, 1.71 (SD, 1.31) at 2-4 weeks, and 2.01 (SD, 1.42) at 20-24 weeks. Follow-up imaging at 20-24 weeks showed no local progression in 42 of 65 patients (64.6%). Six patients died 24-52 weeks after the procedure. No procedure-related complications were reported. CONCLUSION. Microwave ablation is efficacious in alleviating pain due to osseous metastases. The modality has promise for locoregional control of metastases, particularly in the context of oligometastatic (limited disseminated) disease.

7.
J Immunol ; 198(10): 3978-3988, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28381640

RESUMO

B cell development in Justy mutant mice is blocked due to a precursor mRNA splicing defect that depletes the protein GON4-like (GON4L) in B cell progenitors. Genetic and biochemical studies have suggested that GON4L is a transcriptional regulator that coordinates cell division with differentiation, but its role in B cell development is unknown. To understand the function of GON4L, we characterized B cell differentiation, cell cycle control, and mitotic gene expression in GON4L-deficient B cell progenitors from Justy mice. We found that these cells established key aspects of the transcription factor network that guides B cell development and proliferation and rearranged the IgH gene locus. However, despite intact IL-7 signaling, GON4L-deficient pro-B cell stage precursors failed to undergo a characteristic IL-7-dependent proliferative burst. These cells also failed to upregulate genes required for mitotic division, including those encoding the G1/S cyclin D3 and E2F transcription factors and their targets. Additionally, GON4L-deficient B cell progenitors displayed defects in DNA synthesis and passage through the G1/S transition, contained fragmented DNA, and underwent apoptosis. These phenotypes were not suppressed by transgenic expression of prosurvival factors. However, transgenic expression of cyclin D3 or other regulators of the G1/S transition restored pro-B cell development from Justy progenitor cells, suggesting that GON4L acts at the beginning of the cell cycle. Together, our findings indicate that GON4L is essential for cell cycle progression and division during the early stages of B cell development.


Assuntos
Mitose , Proteínas Nucleares/deficiência , Proteínas Nucleares/fisiologia , Células Precursoras de Linfócitos B/fisiologia , Animais , Linfócitos B/fisiologia , Ciclo Celular , Proteínas de Ciclo Celular , Divisão Celular , Proliferação de Células , Proteínas Correpressoras , Ciclina D3/genética , Proteínas de Ligação a DNA , Fator de Transcrição E2F4/genética , Fator de Transcrição E2F4/metabolismo , Regulação da Expressão Gênica , Interleucina-7/imunologia , Interleucina-7/metabolismo , Camundongos , Proteínas Nucleares/genética
8.
Linacre Q ; 86(4): 275-282, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32431420

RESUMO

Brain death during the second trimester of pregnancy creates a unique situation in which the mother is deceased, but life of the developing fetus still depends on somatic functions in the mother's body. In this article, I show that when a pregnant woman becomes brain dead during the second trimester, it is morally licit, though not morally obligatory, to continue somatic support while the fetus develops. The interventions on the mother's body are justified for the life of the fetus, especially in light of the unique mother-child dyad and the responsibilities the mother has for her child. However, this therapy is not frequently employed, and its success is unpredictable. In many cases, the expense and uncertain nature of the therapy may make it disproportionate. In such cases, somatic support of the mother's body may be discontinued. SUMMARY: When brain death is diagnosed during pregnancy, it is a challenging decision whether to use artificial ventilation and other heroic measures to support the developing fetus. This paper demonstrates that while these interventions are acceptable, they are not obligatory.

9.
Linacre Q ; 86(2-3): 225-230, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-32431412

RESUMO

Marriage has been associated with improved pregnancy outcomes. However, as Americans become increasingly accepting of pregnancy and childbearing outside of marriage, many believe the father can support the mother without the parents being married. Some question whether the present normalization of childbearing outside of marriage will negate the protective effect of marriage on pregnancy outcomes. Data from the Centers for Disease Control and Prevention Pregnancy Risk Assessment Monitoring System were used to obtain data from a sample of 138,118 live singleton deliveries from 2012 to 2014. Odds ratios were compared between married and unmarried mothers for outcomes of preterm delivery, a small for gestational age infant, neonatal intensive care unit admission, vaginal delivery, and breastfeeding initiation. Logistic regression analyses were used to adjust for maternal age, maternal and paternal race, maternal medical comorbidities, maternal smoking status, and receipt of Medicaid. Adjusted odds ratios (AOR) showed married women had a lower risk of preterm delivery (AOR = .877, 95% confidence interval [CI; .811-.948]), a small for gestational age baby (AOR = .838, 95% CI [.726-.967]), and a neonatal intensive care admission (AOR = .808, 95% CI [.754-.866]). Women who were married were more likely to have a vaginal delivery (AOR = 1.144, 95% CI [1.085-1.211]) and to initiate breastfeeding (AOR = 1.601, 95% CI [1.490-1.719]). These data demonstrate that despite a normalization in society of childbearing outside of marriage, there continues to be an association of marriage with improved birth outcomes. Summary: Marriage is associated with a lower risk of preterm delivery, small for gestational age infants, and neonatal intensive care unit admission. These differences persist even after correcting for potentially confounding socioeconomic factors.

10.
Immunology ; 155(2): 225-237, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29750331

RESUMO

Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female non-obese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary-gland-protective regulatory T (Treg) cells. Transfer of cervical lymph node (LN) cells from female NOD mice into sex-matched NOD-severe combined immunodeficient (SCID) recipients resulted in sialadenitis, regardless of the presence or absence of Treg cells. In contrast, transfer of cervical LN cells from male NOD mice into sex-matched NOD-SCID recipients only resulted in sialadenitis when Treg cells were depleted before transfer, suggesting that male NOD mice have functional salivary-gland-protective Treg cells. Notably, the host environment affected the ability of Treg cells to prevent sialadenitis with testosterone promoting salivary gland protection. Treg cells from male mice did not protect against sialadenitis in female recipients. Testosterone treatment of female recipients of bulk cervical LN cells decreased sialadenitis, and Treg cells from female mice were capable of protecting against development of sialadenitis in male recipients. Hence, our data demonstrate that female NOD mice develop sialadenitis through a defect in salivary-gland-protective Treg cells that can be reversed in the presence of testosterone.


Assuntos
Glândulas Salivares/imunologia , Sialadenite/etiologia , Sialadenite/metabolismo , Síndrome de Sjogren/etiologia , Síndrome de Sjogren/metabolismo , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos NOD , Glândulas Salivares/metabolismo , Sialadenite/patologia , Sialadenite/terapia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/terapia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
11.
Int J Mol Sci ; 19(10)2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30347820

RESUMO

Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other potentially disease-relevant genes (Epsti1, Ubd) were upregulated in male lacrimal glands. Expression of Cxcl9 and Ccl19, in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, Ifnar1-deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.


Assuntos
Dacriocistite/metabolismo , Interferon Tipo I/metabolismo , Síndrome de Sjogren/metabolismo , Animais , Células Cultivadas , Quimiocina CCL19/metabolismo , Quimiocina CXCL9/metabolismo , Feminino , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transdução de Sinais , Linfócitos T Reguladores/metabolismo
12.
Immunol Cell Biol ; 95(8): 684-694, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28465508

RESUMO

Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LNs) of NOD mice into NOD-severe combined immunodeficiency recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells have a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Epiteliais/imunologia , Aparelho Lacrimal/patologia , Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologia , Transferência Adotiva , Animais , Autoimunidade , Linfócitos T CD8-Positivos/transplante , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Citotoxicidade Imunológica , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID
13.
BMC Health Serv Res ; 17(1): 780, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29179778

RESUMO

BACKGROUND: Recognition of a need for patient-centred care is not new, however making patient-centred care a reality remains a challenge to organisations. We need empirical studies to extend current understandings, create new representations of the complexity of patient-centred care, and guide collective action toward patient-centred health care. To achieve these ends, the research aim was to empirically determine what organisational actions are required for patient-centred care to be achieved. METHODS: We used an established participatory concept mapping methodology. Cross-sector stakeholders contributed to the development of statements for patient-centred care requirements, sorting statements into groupings according to similarity, and rating each statement according to importance, feasibility, and achievement. The resultant data were analysed to produce a visual concept map representing participants' conceptualisation of patient-centred care requirements. Analysis included the development of a similarity matrix, multidimensional scaling, hierarchical cluster analysis, selection of the number of clusters and their labels, identifying overarching domains and quantitative representation of rating data. RESULTS: The outcome was the development of a conceptual map for the Requirements of Patient-Centred Care Systems (ROPCCS). ROPCCS incorporates 123 statements sorted into 13 clusters. Cluster labels were: shared responsibility for personalised health literacy; patient provider dynamic for care partnership; collaboration; shared power and responsibility; resources for coordination of care; recognition of humanity - skills and attributes; knowing and valuing the patient; relationship building; system review evaluation and new models; commitment to supportive structures and processes; elements to facilitate change; professional identity and capability development; and explicit education and learning. The clusters were grouped into three overarching domains, representing a cross-sectoral approach: humanity and partnership; career spanning education and training; and health systems, policy and management. Rating of statements allowed the generation of go-zone maps for further interrogation of the relative importance, feasibility, and achievement of each patient-centred care requirement and cluster. CONCLUSION: The study has empirically determined requirements for patient-centred care through the development of ROPCCS. The unique map emphasises collaborative responsibility of stakeholders to ensure that patient-centred care is comprehensively progressed. ROPCCS allows the complex requirements for patient-centred care to be understood, implemented, evaluated, measured, and shown to be occurring.


Assuntos
Formação de Conceito , Assistência Centrada no Paciente , Análise por Conglomerados , Processos Grupais , Pesquisa sobre Serviços de Saúde , Humanos , Análise Multivariada
15.
J Pediatr Hematol Oncol ; 38(3): 227-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26583624

RESUMO

The increasing use of serial multimodality imaging in the management of pediatric osteosarcoma raises concern of over exposure to ionizing radiation in children, especially from repeated computed tomographic (CT) scans. This study reviews the utilization of multimodality imaging in patients with osteosarcoma at our institution and analyzes any potential radiation-related complications. Twenty-eight patients were identified. Three patients developed late complications-acute myeloid leukemia, myelodysplastic syndrome, and early menopause. Using the patient's age and body part imaged, CT dose length product and effective dose was estimated with the use of a conversion factor for 19 patients. The effective doses were higher in the 3 patients with late complications than the other patients in the cohort (P=0.018). These results suggest an increased risk for adverse effects with higher CT exposures and effective doses. On the basis of our data and published data, methods to decrease the doses of radiation from medical imaging need to be explored. The number of CT scans may be limited. Implementing the Image Gently concept to decrease radiation exposure can be beneficial in modification of CT acquisition parameters.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Osteossarcoma/diagnóstico por imagem , Lesões por Radiação/epidemiologia , Tomografia Computadorizada por Raios X/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Imagem Multimodal/efeitos adversos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Doses de Radiação , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
16.
J Gen Virol ; 96(Pt 1): 24-29, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25228492

RESUMO

Bats have been found to harbour a number of new emerging viruses with zoonotic potential, and there has been a great deal of interest in identifying novel bat pathogens to determine the risk to human and animal health. Many groups have identified novel viruses in bats by detection of viral nucleic acid; however, virus isolation is still a challenge, and there are few reports of viral isolates from bats. In recent years, our group has developed optimized procedures for virus isolation from bat urine, including the use of primary bat cells. In previous reports, we have described the isolation of Hendra virus, Menangle virus and Cedar virus in Queensland, Australia. Here, we report the isolation of four additional novel bat paramyxoviruses from urine collected from beneath pteropid bat (flying fox) colonies in Queensland and New South Wales during 2009-2011.


Assuntos
Quirópteros/virologia , Paramyxovirinae/genética , Paramyxovirinae/isolamento & purificação , Urina/virologia , Animais , Austrália , Infecções por Paramyxoviridae/virologia , Zoonoses/virologia
17.
Virol J ; 12: 107, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26184657

RESUMO

BACKGROUND: In 2008-09, evidence of Reston ebolavirus (RESTV) infection was found in domestic pigs and pig workers in the Philippines. With species of bats having been shown to be the cryptic reservoir of filoviruses elsewhere, the Philippine government, in conjunction with the Food and Agriculture Organization of the United Nations, assembled a multi-disciplinary and multi-institutional team to investigate Philippine bats as the possible reservoir of RESTV. METHODS: The team undertook surveillance of bat populations at multiple locations during 2010 using both serology and molecular assays. RESULTS: A total of 464 bats from 21 species were sampled. We found both molecular and serologic evidence of RESTV infection in multiple bat species. RNA was detected with quantitative PCR (qPCR) in oropharyngeal swabs taken from Miniopterus schreibersii, with three samples yielding a product on conventional hemi-nested PCR whose sequences differed from a Philippine pig isolate by a single nucleotide. Uncorroborated qPCR detections may indicate RESTV nucleic acid in several additional bat species (M. australis, C. brachyotis and Ch. plicata). We also detected anti-RESTV antibodies in three bats (Acerodon jubatus) using both Western blot and ELISA. CONCLUSIONS: The findings suggest that ebolavirus infection is taxonomically widespread in Philippine bats, but the evident low prevalence and low viral load warrants expanded surveillance to elaborate the findings, and more broadly, to determine the taxonomic and geographic occurrence of ebolaviruses in bats in the region.


Assuntos
Quirópteros/virologia , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/veterinária , Animais , Anticorpos Antivirais/sangue , Análise por Conglomerados , Ensaio de Imunoadsorção Enzimática , Doença pelo Vírus Ebola/virologia , Orofaringe/virologia , Filipinas , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Homologia de Sequência
18.
Protein Expr Purif ; 116: 19-29, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26196500

RESUMO

Hendra virus (family Paramyxoviridae) is a negative sense single-stranded RNA virus (NSRV) which has been found to cause disease in humans, horses, and experimentally in other animals, e.g. pigs and cats. Pteropid bats commonly known as flying foxes have been identified as the natural host reservoir. The Hendra virus nucleocapsid protein (HeV N) represents the most abundant viral protein produced by the host cell, and is highly immunogenic with naturally infected humans and horses producing specific antibodies towards this protein. The purpose of this study was to express and purify soluble, functionally active recombinant HeV N, suitable for use as an immunodiagnostic reagent to detect antibodies against HeV. We expressed both full-length HeV N, (HeV NFL), and a C-terminal truncated form, (HeV NCORE), using a bacterial heterologous expression system. Both HeV N constructs were engineered with an N-terminal Hisx6 tag, and purified using a combination of immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC). Purified recombinant HeV N proteins self-assembled into soluble higher order oligomers as determined by SEC and negative-stain transmission electron microscopy. Both HeV N proteins were highly immuno-reactive with sera from animals and humans infected with either HeV or the closely related Nipah virus (NiV), but displayed no immuno-reactivity towards sera from animals infected with a non-pathogenic paramyxovirus (CedPV), or animals receiving Equivac® (HeV G glycoprotein subunit vaccine), using a Luminex-based multiplexed microsphere assay.


Assuntos
Vírus Hendra/química , Vírus Hendra/imunologia , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Clonagem Molecular , Escherichia coli/genética , Expressão Gênica , Vírus Hendra/genética , Vírus Hendra/ultraestrutura , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/virologia , Cavalos , Humanos , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/ultraestrutura , Plasmídeos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/ultraestrutura , Suínos
19.
Adv Health Sci Educ Theory Pract ; 20(2): 325-38, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25008246

RESUMO

Patient encounters are central to the provision of learning opportunities for medical students and their development as medical professionals. The primary aim of the study reported in this paper was to discover how partnering medical students with patients with chronic illness in undergraduate learning influenced the development of a patient centred professional identity and professionalism. An exploratory interpretive research design was used to address the research aim within a patient partner program (P3). Three qualitative data collection methods were used: (1) focus groups (2) extended response questionnaire and (3) semi-structured interviews. Data were coded and analysed thematically. The professional identity of medical students is constructed along traditional lines in the preclinical years. Patient-partnership offers a disruption to this development by way of an intersection with patients with chronic illness which potentially allows meaningful construction of what a patient-centred identity should be. This point of reflection provides an opportunity to engage at a higher level in medical identity development and professionalism. The findings discussed in this paper further stimulate the patient-centred agenda by understanding the conflict associated with the student-patient nexus in medical education and its potential for building professionalism and a patient-centred professional identity. To continue the drive for a patient-centred professional identity there must be ongoing engagement with patients in medical education, preferably commencing early in a student's journey so that it becomes the expected norm. This study has highlighted that a true patient-centred emphasis is being encountered too late in their socialisation process.


Assuntos
Educação de Graduação em Medicina/métodos , Aprendizagem , Papel do Médico , Relações Médico-Paciente , Estudantes de Medicina , Doença Crônica/psicologia , Doença Crônica/terapia , Humanos , Cultura Organizacional , Assistência Centrada no Paciente , Pesquisa Qualitativa
20.
J Contin Educ Nurs ; 46(3): 129-33, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25730468

RESUMO

BACKGROUND: Nurses from various setting lack sufficient knowledge about diabetes and diabetes management. Better understand of evidence-based practices by nurses who are involved in caring for hospitalized individuals with diabetes can positively influence care outcomes. METHOD: A pretest design was used to evaluate the effectiveness of a diabetes education program for RNs working voluntarily participated. A 1-day education program was developed and delivered to the participating nurses. Knowledge regarding diabetes was tested before and after the education program. RESULTS: a significant difference was noted in the modified diabetes basic knowledge mean test scores before and after implementation of the education program (t[128] = 17.95, P < 0.001). CONCLUSIONS: The diabetes education program had a positive on nurses' knowledge. This finding has implications for developing diabetes education content within nursing curricula, as well as continuing education courses for practicing nurses.


Assuntos
Diabetes Mellitus/enfermagem , Educação Continuada em Enfermagem/organização & administração , Avaliação Educacional , Enfermagem Baseada em Evidências/educação , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Currículo , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Avaliação de Programas e Projetos de Saúde , Estados Unidos , Adulto Jovem
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