ORCID Profile
0000-0002-4795-5539
Current Organisations
National Taipei University of Technology
,
James Cook University
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Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.DIAGMICROBIO.2013.07.009
Abstract: Melioidosis is caused by the Gram negative bacterium Burkholderia pseudomallei. The gold standard for diagnosis is culture, which requires at least 3-4 days obtaining a result, hindering successful treatment of acute disease. The existing indirect haemagglutination assay (IHA) has several disadvantages, in that approximately half of patients later confirmed culture positive are not diagnosed at presentation and a subset of patients are persistently seronegative. We have developed 2 serological assays, an enzyme-linked immunosorbent assay (ELISA), and a 2-dimensional immunoarray (2DIA), capable of detecting antibodies in patient sera from a greater proportion of IHA-negative patient subsets. The 2DIA format can distinguish between different LPS serotypes. Currently, the 2DIA has a sensitivity and specificity of 100% and 87.1%, respectively, with 100% of culture-positive, IHA-negative s les detected. The ELISA has a sensitivity and specificity of 86.2% and 93.5%, respectively, detecting 67% of culture-positive, IHA-negative s les. The ELISA and 2DIA tests described here are more rapid and reliable for serological testing compared to the existing IHA.
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.MICINF.2005.04.013
Abstract: Burkholderia pseudomallei, the etiological agent of melioidosis, causes significant mortality in endemic regions, but little is known regarding the immune mechanisms required for successful protective immunity. To establish a model of immunization that could be used to study this we screened a library of B. pseudomallei strains for immunogenicity in mice. BALB/c mice were immunized with test strains, and 2 weeks later were given a lethal challenge (LC) of virulent B. pseudomallei. Among 49 strains tested, a single strain, CL04, exhibited strong immunoprotective capacity. Interestingly, CL04 had been cultured from a patient with chronic colonization of B. pseudomallei, which is a rare phenomenon. Mice immunized with 0.1 x LD50 (5 x 10(3) CFU) of CL04 had significantly better survival and lower bacterial loads after LC compared to naïve controls. Dose-response analysis demonstrated more robust immunity after higher immunizing doses, and bacterial inactivation by gamma irradiation diminished the protective effect, indicating a requirement for viable organism for immunity. CL04-induced immunity was demonstrated both in B. pseudomallei-susceptible BALB/c and -resistant C57BL/6 mice. We investigated the gene profile of CL04-induced immunity by analyzing responses to immunization using cDNA microarray. Unique responses involving granulocyte macrophage colony stimulating factor (GM-CSF), the proapoptotic regulator Bad and cyclin-dependent kinase (CDK5) were detected in immunized mice, but these responses were absent in naïve-LC mice. Further, responses differed between mouse strains, indicating dependence on host genetic background. This model will be useful in identifying elements of the immune response required for successful adaptive immunity against B. pseudomallei.
Publisher: Elsevier BV
Date: 10-2004
Publisher: American Society for Microbiology
Date: 06-2012
DOI: 10.1128/IAI.00212-12
Abstract: Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei . Type 2 diabetes (T2D) is the most common comorbidity associated with melioidosis. B. pseudomallei isolates from melioidosis patients with T2D are less virulent in animal models than those from patients with melioidosis and no identifiable risk factors. We developed an ex vivo whole-blood assay as a tool for comparison of early inflammatory profiles generated by T2D and nondiabetic (ND) in iduals in response to a B. pseudomallei strain of low virulence. Peripheral blood from in iduals with T2D, with either poorly controlled glycemia (PC-T2D [ n = 6]) or well-controlled glycemia (WC-T2D [ n = 8]), and healthy ND ( n = 13) in iduals was stimulated with B. pseudomallei . Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1β, and IL-10) were also determined. Following stimulation, oxidative burst and MPO levels were significantly elevated in blood from PC-T2D subjects compared to controls. Differences were also observed in expression of Toll-like receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND in iduals. Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects compared to ND in iduals. Notably, differential inflammatory responses of PC-T2D, WC-T2D, and ND in iduals to B. pseudomallei occur independently of bacterial load and confirm the efficacy of this model of T2D-melioidosis comorbidity as a tool for investigation of dysregulated PMN and monocyte responses to B. pseudomallei underlying susceptibility of T2D in iduals to melioidosis.
Publisher: Oxford University Press (OUP)
Date: 04-2008
Publisher: Wiley
Date: 08-04-2010
DOI: 10.1111/J.1365-2702.2009.02993.X
Abstract: Objective. To implement and evaluate strategies suggested by general nurses to improve management of children and adolescents with mental health problems admitted to a paediatric unit of a general hospital. Background. The first phase of a study using a Participatory Action Research approach identified several concerns associated with general nurses providing care to young people with mental disorders in paediatric units of general hospitals, together with suggestions for strategies to address these issues. This paper describes the second and third phase of the Participatory Action Research study, involving the implementation and evaluation of these strategies. Design. Participatory Action Research. Methods. Actions that occurred during phase two of the Participatory Action Research study included revision and introduction of policies and procedures for mental health care in the unit, education and training sessions for paediatric nursing staff and opportunities to strengthen communication between existing mental health services. In phase three, two focus groups were conducted to explore current perceptions of mental health care delivery in the unit and evaluate change, following phase two. Results. Changes in clinical practice for paediatric mental health care were acknowledged by participants. Reflection has assisted nurses to better understand their strengths and weaknesses and to acknowledge and challenge the assumptions on which their ideas, feelings and actions about patients with mental health issues are based. Participants also recognised the existing skills and expertise they possess that are relevant to the management of young people with a mental health problem, although they continue to seek ongoing education and support in this field. Conclusions. This study demonstrates that through Participatory Action Research it is possible to enhance mental health nursing care in a rural paediatric unit. Relevance to clinical practice. Such changes have the potential to improve the experience of young people and their families whilst receiving treatment for mental health conditions in a general paediatric unit.
Publisher: Oxford University Press (OUP)
Date: 12-2008
Publisher: Oxford University Press (OUP)
Date: 03-2011
Publisher: American Society for Microbiology
Date: 02-2013
DOI: 10.1128/IAI.00930-12
Abstract: Bacterial infections are a common and serious complication of type 2 diabetes (T2D). The prevalence of melioidosis, an emerging tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei , is increased in people with T2D. This is the first study to compare murine models of T2D and melioidosis. Susceptibility and disease progression following infection with B. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic model of T2D. The metabolic profile of mice with diet-induced diabetes, including body weight, blood glucose, cholesterol, triglycerides, insulin resistance, and baseline levels of inflammation, closely resembled that of clinical T2D. Following subcutaneous infection with B. pseudomallei , bacterial loads at 24 and 72 h postinfection in the blood, spleen, liver, lungs, and subcutaneous adipose tissue (SAT) at the site of infection were compared in parallel with the expression of inflammatory cytokines and tissue histology. As early as 24 h postinfection, the expression of inflammatory (interleukin-1β [IL-1β], tumor necrosis factor alpha [TNF-α], and IL-6) and T H 1 (IL-12 and gamma interferon [IFN-γ]) cytokines was impaired in diabetic mice compared to nondiabetic littermates. Early differences in cytokine expression were associated with excessive infiltration of polymorphonuclear neutrophils (PMN) in diabetic mice compared to nondiabetic littermates. This was accompanied by bacteremia, hematogenous dissemination of bacteria to the lungs, and uncontrolled bacterial growth in the spleens of diabetic mice by 72 h postinfection. The findings from our novel model of T2D and melioidosis comorbidity support the role of impaired early immune pathways in the increased susceptibility of in iduals with T2D to bacterial infections.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-06-2019
DOI: 10.1097/TA.0000000000002397
Abstract: Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg 2+ (ALM) bolus and 4 hours 0.9% NaCl/ALM “drip” in a rat model of uncontrolled hemorrhagic shock. Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization “drip” (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-cl ed and stored at −80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of -k, mtCO3, PGC-1α, and sirt-1 genes were determined. Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours ( p 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of -k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls ( p 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, -k, sirt-1, and mtCO3 gene expression in liver was significantly 29–41% lower in the ALM group compared with controls, and PGC-1α was 75% lower. Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of -k, PGC-1α, sirt-1, and mtCO3 to presumably “boost” mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.MICINF.2011.07.008
Abstract: This study used a murine model of type 2 diabetes (BKS.Cg-Dock7(m) +/+Lepr(db)/J mice) to investigate the inflammatory and cellular mechanisms predisposing to Burkholderia pseudomallei infection and co-morbid diabetes. Homozygous db/db (diabetic) mice developed extreme obesity, dyslipidaemia and glucose intolerance leading to hyperglycaemia and overt type 2 diabetes. Compared to their heterozygous db/+ (non-diabetic) littermates, diabetic mice rapidly succumbed to subcutaneous B. pseudomallei infection, paralleled by severe hypoglycaemia and increased expression of the proinflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β, in the spleen, despite comparable bacterial loads in the spleen of non-diabetic mice. Neutrophil oxidative burst and dendritic cell uptake and killing of B. pseudomallei were similar between diabetic and non-diabetic mice. Compared to peritoneal macrophages from non-diabetic mice, macrophages from diabetic mice were unable to contain and kill B. pseudomallei. Functional differences between macrophages of diabetic and non-diabetic mice toward B. pseudomallei may contribute to rapid dissemination and more severe disease progression in hosts with co-morbid type 2 diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
Publisher: Elsevier BV
Date: 07-2001
DOI: 10.1016/S1286-4579(01)01417-4
Abstract: Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are protean, but the mechanisms underlying development of the different forms of disease remain poorly understood. In murine melioidosis, the level of virulence of B. pseudomallei is important in disease pathogenesis and progression. In this study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence of a library of clinical and environmental B. pseudomallei isolates from Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-)) isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations between virulence and disease presentation in patients however, this was not a consistent observation. Virulence did not correlate with isolate origin (i.e. clinical vs environmental), since numerous ara(-) environmental isolates were highly virulent. The least virulent isolate was a soil isolate from Papua New Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei virulence was investigated by in vivo passage of isolates through mice and repetitive in vitro subculture. Virulence increased following in vivo exposure in only one of eight isolates tested. In vitro subculture on ferric citrate-containing medium caused attenuation of virulence, and this correlated with changes in colony morphology. Pulsed-field gel electrophoresis and randomly lified polymorphic DNA typing demonstrated that selected epidemiologically related isolates that had variable clinical outcomes and different in vivo virulence were clonal strains. No molecular changes were observed in isolates after in vivo or in vitro exposure despite changes in virulence. These results indicate that virulence of selected B. pseudomallei isolates is variable, being dependent on factors such as iron bioavailability. They also support the importance of other variables such as inoculum size and host risk factors in determining the clinical severity of melioidosis.
Publisher: Oxford University Press (OUP)
Date: 15-07-2002
DOI: 10.1086/341222
Abstract: Melioidosis is a bacterial infection caused by Burkholderia pseudomallei. The aim of this study was to determine whether a cell-mediated adaptive immune response against B. pseudomallei developed in patients who had recovered from melioidosis. Lymphocyte proliferation assays were done on peripheral blood mononuclear cells from patients (n=13) and control subjects (n=10) to determine the lymphocyte response to B. pseudomallei antigens. Production of interferon-gamma and interleukin-10 was also determined. Activation of T cell subsets was assessed by fluorescence-activated cell sorter analysis, using antibodies to CD4, CD8, and CD69 antigens. Lymphocyte proliferation and interferon-gamma production in response to B. pseudomallei antigens were significantly higher (P<.001 for both) in patients than in control subjects. There was also an increase in the percentage of activated CD4+ (P<.004) and activated CD8+ T cells (P<.035) in cell cultures from patients. The development of such a cell-mediated immune response in patients may be essential for their survival.
Publisher: Springer Science and Business Media LLC
Date: 15-04-2019
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2015
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 05-2017
Publisher: Springer Science and Business Media LLC
Date: 28-06-2019
DOI: 10.1038/S41598-019-45871-Z
Abstract: Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis %. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 04-2005
Publisher: Wiley
Date: 10-11-2009
DOI: 10.1111/J.1365-2702.2008.02567.X
Abstract: To explore the experiences of general nurses towards caring for children with mental health issues and to identify strategies to improve management of these children. There has been an increase of children and adolescents with complex emotional and psychological disorders being admitted to paediatric units of general hospitals due to a lack of specialist child and youth mental health facilities. The study is situated in a 16 bed paediatric unit of a rural public hospital. As the closest inpatient child mental health unit of this kind is more than 600 km away, the paediatric unit admits children and adolescents with a primary psychiatric diagnosis. A participatory action research approach guided this study. Focus groups and in idual interviews were conducted with a purposive convenience s le of all nursing staff (n = 20) working in the paediatric unit. Verbatim interview transcripts were analysed to identify the major themes. Two main themes emerged from data analysis: (1) role preparation and adequacy (2) lack of support and resources. Participants suggested several strategies to address these concerns including: improving relationships with mental health services, professional development, and developing a greater appreciation for mental health interventions. There is a clear need for an increased understanding of mental health practices, an improved relationship between general and mental health services and continuing professional development to ensure nurses possess the skills and confidence to provide quality care to children admitted to a paediatric unit with a mental health diagnosis. Few general nurses have mental health training and, through no fault of their own, may be providing less than optimal care to children who are admitted with a mental health diagnosis. Through a desire to improve care, the following participatory action research project was instigated.
Publisher: Wiley
Date: 06-01-2015
DOI: 10.1111/IMM.12394
Publisher: Elsevier BV
Date: 03-2019
Publisher: Wiley
Date: 10-2001
DOI: 10.1046/J.1440-1711.2001.01038.X
Abstract: Melioidosis is a disease of the tropics caused by the facultative intracellular bacterium Burkholderia pseudomallei. In human infection, increased levels of IFN-gamma in addition to the chemokines interferon-gamma-inducible protein 10 (IP-10) and monocyte interferon-gamma-inducible protein (Mig) have been demonstrated. However, the role of these and other chemokines in the pathogenesis of melioidosis remains unknown. Using BALB/c and C57BL/6 mice as models of the acute and chronic forms of human melioidosis, the induction of mRNA was assessed for various chemokines and CSF (G-CSF, M-CSF, GM-CSF, IP-10, Mig, RANTES, MCP-1, KC and MIP-2) in spleen and liver following B. pseudomallei infection. Patterns of chemokine and CSF induction were similar in liver and spleen however, responses were typically greater in spleen, which reflected higher tissue bacterial loads. In BALB/c mice, high-level expression of mRNA for all chemokines and CSF investigated was demonstrated at day 3 postinfection, correlating with peak bacterial load and extensive infiltration of leucocytes. In contrast, increased mRNA expression and bacterial numbers in C57BL/6 mice were greatest between 4 and 14 days following infection. This paralleled increases in the size and number of abscesses in liver and spleen of C57BL/6 mice at days 3 and 14 postinfection. Earlier induction of cytokine-induced neutrophil chemoattractant (KC), macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) mRNA was demonstrated in spleen, while MIP-2, MCP-1, IP-10 and Mig were demonstrated in liver of BALB/c mice when compared to spleen and liver of C57BL/6. The magnitude of cellular responses observed in the tissue correlated with increased levels of the chemokines and CSF investigated, as well as bacterial load. Compared with C57BL/6 mice, greater infiltration of neutrophils was observed in liver and spleen of BALB/c mice at day 3. In contrast, early lesions in C57BL/6 mice predominantly comprised macrophages. These results suggest that the inability of BALB/c mice to contain the infection at sites of inflammation may underlie the susceptible phenotype of this mouse strain towards B. pseudomallei infection.
Publisher: Wiley
Date: 12-06-2007
Abstract: Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia pseudomallei. The current study was carried out to determine the mechanisms involved in the development of protective immunity in a murine model of melioidosis. Following intravenous infection with B. pseudomallei, both C57BL/6 and BALB/c mice demonstrated delayed-type hypersensitivity responses and lymphocyte proliferation towards B. pseudomallei antigens, indicating the generation of B. pseudomallei-specific lymphocytes. Adoptive transfer of these lymphocytes to naïve C57BL/6 mice was demonstrated by a delayed-type hypersensitivity response. Mice were not protected from a subsequent lethal challenge with a highly virulent strain of B. pseudomallei, suggesting that a single intravenous dose of the bacterium is insufficient to induce a protective adaptive immune response. Attempts to induce resistance in susceptible BALB/c mice used repetitive low-dose exposure to live B. pseudomallei. Immune responses and resistance following subcutaneous immunization with live B. pseudomallei were compared with exposure to heat-killed, culture filtrate and sonicated B. pseudomallei antigens. Compared to heat-killed B. pseudomallei, significant protection was generated in BALB/c mice following immunization with live bacteria. Our studies also demonstrate that the type of immune response generated in vivo is influenced by the antigenic preparation of B. pseudomallei used for immunization.
Publisher: Wiley
Date: 18-11-2019
Abstract: Organic semiconductors demonstrate several advantages over conventional inorganic materials for novel electronic and optoelectronic applications, including molecularly tunable properties, flexibility, low‐cost, and facile device integration. However, before organic semiconductors can be used for the next‐generation devices, such as ultrafast photodetectors (PDs), it is necessary to develop new materials that feature both high mobility and ambient stability. Toward this goal, a highly stable PD based on the organic single crystal [PtBr 2 (5,5′‐bis(CF 3 CH 2 OCH 2 )‐2,2′‐bpy)] (or “Pt complex (1o)”) is demonstrated as the active semiconductor channel—a material that features a lamellar molecular structure and high‐quality, intraligand charge transfer. Benefitting from its unique crystal structure, the Pt‐complex (1o) device exhibits a field‐effect mobility of ≈0.45 cm 2 V −1 s −1 without loss of significant performance under ambient conditions even after 40 days without encapsulation, as well as immersion in distilled water for a period of 24 h. Furthermore, the device features a maximum photoresponsivity of 1 × 10 3 A W −1 , a detectivity of 1.1 × 10 12 cm Hz 1/2 W −1 , and a record fast response/recovery time of 80/90 µs, which has never been previously achieved in other organic PDs. These findings strongly support and promote the use of the single‐crystal Pt complex (1o) in next‐generation organic optoelectronic devices.
Publisher: Mary Ann Liebert Inc
Date: 2019
DOI: 10.1089/SUR.2018.135
Abstract: Despite significant advancements in surgical protocols and biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a leading cause of implant failure. Staphylococcus aureus nasal colonization is an established risk factor for PJI, with methicillin-sensitive S. aureus a leading cause of orthopedic implant-related infections. The purpose of these in vitro studies was to investigate the antibacterial activity of a tailored bacteriophage cocktail against planktonic and biofilm-associated S. aureus. The S. aureus strains (n = 30) were screened for their susceptibility to a library of S. aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that demonstrated bactericidal activity against >90% of S. aureus strains tested were combined as a StaPhage cocktail and assessed for their antibacterial activity toward planktonic and biofilm-associated S. aureus, with biofilms established on three-dimensional-printed porous titanium scaffolds. StaPhage treatment immediately after bacterial inoculation inhibited growth of S. aureus by >98% in eight hour cultures when multiplicity of infection of phages to bacteria was greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium surfaces were significantly reduced (6.8 log Combined, these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage cocktails against S. aureus growing on porous titanium and warrant further in vivo studies in a clinically relevant animal model to evaluate the potential application of bacteriophage in the management of PJI caused by S. aureus.
Publisher: Springer Science and Business Media LLC
Date: 18-06-2018
Publisher: Wiley
Date: 21-05-2009
DOI: 10.1111/J.1440-1584.2009.01061.X
Abstract: To explore, advance and evaluate mental health practices in a rural general paediatric unit through participatory action research. A participatory action research approach guided this study, providing an opportunity for nursing staff to become actively involved in the design, direction and outcomes of the research. A 16-bed paediatric unit of a rural general hospital. A purposive convenience s le of all paediatric nursing staff (n = 20 of 24 nurses). In the first phase of this study, focus groups were conducted to explore the experiences of nurses. Participants considered mental health to be a specialist discipline area and the role of the mental health nurse to be complex. They felt that their lack of training and experience with mental health issues was detrimental to the delivery of optimal patient care. There was concern about differing approaches to treatment, relationships with other mental health services and the suitability of the ward environment for young people with a mental health problem. Participants called for training by qualified mental health staff and the development of policies and clinical guidelines to facilitate their delivery of care to patients with a mental health problem in an acute medical environment. There is a clear need for nursing specialities to work together to ensure that optimal care is given to patients admitted to general hospital with a mental health issue. Given the absence of accessible specialist child mental health inpatient units in regional and remote areas, upskilling paediatric nurses must be a priority.
Publisher: American Society for Microbiology
Date: 10-2014
DOI: 10.1128/IAI.01880-14
Abstract: Burkholderia pseudomallei , the etiological agent for melioidosis, is an important cause of community-acquired sepsis in northern Australia and northeast Thailand. Due to the rapid dissemination of disease in acute melioidosis, we hypothesized that dendritic cells (DC) could act as a vehicle for dissemination of B. pseudomallei . Therefore, this study investigated the effect of B. pseudomallei infection on DC migration capacity and whether migration of DC enabled transportation of B. pseudomallei from the site of infection. B. pseudomallei stimulated significantly increased migration of bone marrow-derived DC (BMDC), both in vitro and in vivo , compared to uninfected BMDC. Furthermore, migration of BMDC enabled significantly increased in vitro trafficking of B. pseudomallei and in vivo dissemination of B. pseudomallei to secondary lymphoid organs and lungs of C57BL/6 mice. DC within the footpad infection site of C57BL/6 mice also internalized B. pseudomallei and facilitated dissemination. Although DC have previously been shown to kill intracellular B. pseudomallei in vitro , the findings of this study demonstrate that B. pseudomallei -infected DC facilitate the systemic spread of this pathogen.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.SEMARTHRIT.2019.03.008
Abstract: Osteoarthritis (OA) is a leading cause of global disability that affects more than half of the population over 65. It is not a single disease but a progressive, inflammatory- and immune-altering multi-disease that affects the whole joint. OA has many risk factors including age, obesity, gender, lifestyle, joint morphology, metabolic dysfunction and genetic disposition. A major stumbling block in treating clinical OA has been the inability to detect its early onset and disease progression. This gap in understanding may arise from our failure to recognize that the OA patient exhibits a vulnerability to dysregulation of central feedback circuits that control sympathetic tone, inflammation, circadian rhythms (central and peripheral clocks), gut microbiome, metabolic redox and whole joint pathology. Early detection of OA and slowing its progression may come from discoveries outside the joint targeting these potentially modifiable upstream targets. We argue that future treatments may benefit from moving from a knee-centric viewpoint to a more systems-based, whole-body approach. The challenge, however, will be to better characterize these key circuits and apply this knowledge to develop new therapies and interventions.
Publisher: Oxford University Press (OUP)
Date: 02-2008
DOI: 10.1097/NEN.0B013E3181633526
Abstract: To determine the reliability of assessment of alpha-synuclein-immunoreactive (alphaS-IR) structures by neuropathologists, 28 evaluators from 17 centers of BrainNet Europe examined current methods and reproducibility of alphaS-IR evaluation using a tissue microarray (TMA) technique. Tissue microarray blocks were constructed of s les from the participating centers that contained alphaS-IR structures. Slides from these blocks were stained in each center and assessed for neuronal perikaryal inclusions, neurites, and glial cytoplasmic inclusions. The study was performed in 2 phases. First, the TMA slides were stained with the antibody of the center's choice. In this phase, 59% of the sections were of good or acceptable quality, and 4 of 9 antibodies used performed consistently. Differences in interpretation and categorization of alphaS-IR structures, however, led to differing results between the laboratories. Prior to the second phase, the neuropathologists participated in a training session on the evaluation of alphaS-IR structures. Based on the results of the first phase, selected antibodies using designated antigen retrieval methods were then applied to TMA slides in the second phase. When the designated methods of both staining and evaluation were applied, all 26 subsequently stained TMA sections evaluated were of good/acceptable quality, and a high level of concordance in the assessment of the presence or absence of specific alphaS-IR structures was achieved. A semiquantitative assessment of alphaS-IR neuronal perikaryal inclusions yielded agreements ranging from 49% to 82%, with best concordance in cortical core s les. These results suggest that rigorous methodology and dichotomized assessment (i.e. determining the presence or absence of alphaS-IR) should be applied, and that semiquantitative assessment can be recommended only for the cortical s les. Moreover, the study demonstrates that there are limitations in the scoring of alphaS-IR structures.
Publisher: Oxford University Press (OUP)
Date: 2008
Publisher: The Company of Biologists
Date: 15-09-2019
DOI: 10.1242/BIO.045203
Abstract: Prosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains the leading cause for revision surgery, with Staphylococcus aureus the bacterium most frequently responsible. We describe a novel rat model of implant-associated S. aureus infection of the knee using orthopaedic materials relevant to modern TKA. Male Sprague-Dawley rats underwent unilateral knee implant surgery, which involved placement of a cementless, porous titanium implant into the femur, and an ultra-highly cross-linked polyethyelene (UHXLPE) implant into the proximal tibia within a mantle of gentamicin-laden bone cement. S. aureus biofilms were established on the surface of titanium implants prior to implantation into the femur of infected animals, whilst control animals received sterile implants. Compared to controls, the time taken to full weight-bear and recover pre-surgical body weight was greater in the infected group. Neutrophils and C-reactive protein levels were significantly higher in infected compared to control animals at day 5 post surgery, returning to baseline levels for the remainder of the 28-day experimental period. Blood cultures remained negative and additional plasma inflammatory markers were comparable for control and infected animals, consistent with the clinical presentation of delayed-onset PJI. S. aureus was recovered from joint tissue and implants at day 28 post surgery from all animals that received pre-seeded titanium implants, despite the use of antibiotic-laden cement. Persistent localised infection was associated with increased inflammatory responses and radiological changes in peri-implant tissue. The availability of a preclinical model that is reproducible based on the use of current TKA materials and consistent with clinical features of delayed-onset PJI will be valuable for evaluation of innovative therapeutic approaches.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JOCA.2018.04.018
Abstract: The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-nineteenth century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'. A similar narrative applies to the concept of OA affecting the whole joint vs the 'wear-and-tear' hypothesis, inflammation and the role of the central nervous system (CNS). In the late nineteenth and early twentieth centuries, the Garrods (father and son) and Hermann Senator argued that OA was a whole joint disease, and that inflammation played a major role in its progression. Garrod Jnr and John Spender also linked OA to a neurogenic lesion 'outside the joint'. The remaining twentieth century was no less dynamic, with major advances in basic science, diagnostics, treatments, surgical interventions and technologies. Today, OA is characterized as a multi-disease with inflammation, immune and CNS dysfunction playing central roles in whole joint damage, injury progression, pain and disability. In the current 'omics' era (genomics, proteomics and metabolomics), we owe a great debt to past physicians and surgeons who dared to think 'outside-the-box' to explain and treat OA. Over 130 years later, despite these developments, we still don't fully understand the underlying complexities of OA, and we still don't have a cure.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
DOI: 10.1007/S40279-018-0964-7
Abstract: Several studies have examined the effects of balance training in elderly in iduals following total knee arthroplasty (TKA), although findings appear to be equivocal. This systematic review and meta-analysis examined the effects of balance training on walking capacity, balance-specific performance and other functional outcome measures in elderly in iduals following TKA. Data sources: Pubmed, PEDro, Cinahl, SportDiscus, Scopus. Eligibility criteria: Data were aggregated following the population-intervention-comparison-outcome (PICO) principles. Eligibility criteria included: (1) randomised controlled trials (2) studies with comparative groups (3) training interventions were incorporated post-TKA and (4) outcome measures included walking capacity, balance-specific performance measures, subjective measures of physical function and pain and knee range-of-motion. Elderly in iduals (65 + years) who underwent total knee arthroplasty. Balance interventions that consisted of balance exercises, which were compared to control interventions that did not involve balance exercises, or to a lesser extent. Participants also undertook usual physiotherapy care in conjunction with either the balance and/or control intervention. The intervention duration ranged from 4 to 32 weeks with outcome measures reported immediately following the intervention. Of these, four studies also reported follow-up measures ranging from 6 to 12 months post-interventions. Study appraisal: PEDro scale. Quantitative analysis was conducted by generating forest plots to report on standardised mean differences (SMD i.e. effect size), test statistics for statistical significance (i.e. Z values) and inter-trial heterogeneity by inspecting I Balance training exhibited significantly greater improvement in walking capacity (SMD = 0.57 Z = 6.30 P < 0.001 I A number of outcome measures indicated high inter-trial heterogeneity and only articles published in English were included. Balance training improved walking capacity, balance-specific performance and functional outcome measures for elderly in iduals following TKA. These findings may improve clinical decision-making for appropriate post-TKA exercise prescription to minimise falls risks and optimise physical function.
Publisher: American Society for Microbiology
Date: 15-06-2011
DOI: 10.1128/CVI.00077-11
Abstract: The indirect hemagglutination assay (IHA) is the most frequently used serological test to confirm exposure to Burkholderia pseudomallei . Patients with culture-confirmed disease often have a nonreactive IHA at presentation and occasionally fail to seroconvert on serial testing. We investigated whether using antigens derived from the cultured isolates of persistently IHA-nonreactive patient sera improved the sensitivity of the IHA. In addition, we assessed the antigen-specific lymphocyte response in this group of patients to a panel of B. pseudomallei antigens, including those derived from their own cultured isolates. Eleven patients with culture-proven melioidosis were identified as having persistently IHA-nonreactive sera. A modified IHA using erythrocytes sensitized with patient isolate-derived antigen tested against convalescent-phase serum was performed. The majority (82%) of sera showed a negative (≤1:5) result, one was borderline (1:20), and one was positive at the cutoff value (1:40). IHA-nonreactive sera were also tested by enzyme immunoassay (EIA), with 73% (8/11) demonstrating IgG positivity. In addition, lymphocytes isolated from persistently IHA-nonreactive patient sera demonstrated significantly increased proliferation in response to B. pseudomallei antigens compared to controls. These studies demonstrate the presence of B. pseudomallei -specific antibody by EIA and B. pseudomallei -specific lymphocytes in patient sera categorized as persistently nonreactive according to the IHA. New immunoassays are required and should incorporate B. pseudomallei antigens that are immunoreactive for this subset of IHA-nonreactive patient sera.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.MICINF.2014.12.007
Abstract: Melioidosis sepsis, caused by Burkholderia pseudomallei, is associated with high mortality due to an overwhelming inflammatory response. Plasmacytoid dendritic cells (pDC) are potent producers of type I interferons (IFN). This study investigated whether pDC and type I IFN play a role during the early stages of B. pseudomallei infection. Human and murine pDC internalised and killed B. pseudomallei as efficiently as murine conventional DC (cDC). pDC derived from B. pseudomallei-susceptible (BALB/c) mice demonstrated poor intracellular killing and increased IFN-alpha compared to pDC derived from B. pseudomallei-resistant (C57BL/6) mice. This is the first evidence of pDC bactericidal activity against B. pseudomallei infection.
Publisher: The Company of Biologists
Date: 11-07-2016
DOI: 10.1242/BIO.016790
Abstract: The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy-dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2013
DOI: 10.1007/S12020-013-9874-5
Abstract: Evidence has emerged supporting a link between high glycaemic index (GI) diets and type 2 diabetes (T2D). The aim of this study was to determine if dietary GI influences the development of hyperglycaemia in C57BL/6 mice to more closely reflect T2D. Male C57BL/6 mice (n=30) were randomly ided into 3 dietary groups consisting of either standard rodent chow (4.8 % fat, 20 % protein), or a high fat (HF) diet (21-23 % fat, 19 % protein) with low GI (15.4 % starch HF-LG) or high GI (50.5 % dextrose HF-HG) ad libitum for 10 weeks. Body weight, blood glucose, glucose tolerance, and circulating cholesterol and triglyceride levels were measured for the duration of the study. We found that increasing the GI of a moderately HF diet induces severe hyperglycaemia and insulin resistance in C57BL/6 mice, reflective of criteria for diagnosis of T2D, whilst littermates consuming an equivalent low GI diet maintain glucose homeostasis. This study demonstrates the significant contribution of both dietary carbohydrate and fat composition in the aetiopathogenesis of T2D.
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.NUCMEDBIO.2005.12.014
Abstract: [(99m)Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13018-021-02871-Y
Abstract: Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. Male Sprague–Dawley rats ( n = 24) were randomly ided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68 + cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28. Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.
Publisher: Wiley
Date: 29-08-2023
DOI: 10.1002/PRP2.1133
Abstract: The binding of drugs to plasma proteins is an important consideration in drug development. We have reported that the dose of adenosine, lidocaine, and magnesium (ALM) fluid therapy for resuscitation from hemorrhagic shock is nearly 3‐times higher for pigs than rats. Since lidocaine strongly binds to serum alpha‐1‐acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs. Healthy adult male Sprague–Dawley rats and female crossbred pigs ( n = 33 each) underwent tail vein and peripheral ear vein blood s ling, respectively, to collect plasma for AGP measurements. Rats ( n = 17) and pigs ( n = 16) underwent surgical instrumentation and uncontrolled hemorrhage via liver resection, and were treated with 3% NaCl ± ALM IV bolus followed 60 min later by 4 h 0.9% NaCl ± ALM IV drip. Rats were monitored for 72 h with blood s les taken post‐surgery, and at 5.25, 24, and 72 h. Pigs were monitored for 6 h with blood s les taken post‐surgery, and at 60 min and 6 h. Plasma AGP was measured with rat‐ and pig‐specific enzyme‐linked immunosorbent assay kits. Baseline AGP levels in rats were 3.91 μg/mL and significantly 83‐fold lower than in pigs (325 μg/mL). Surgical instrumentation was associated with ~10‐fold increases in AGP in rats and a 21% fall in pigs. AGP levels remained elevated in rats after hemorrhage and resuscitation (28–29 μg/mL). In contrast, no significant differences in plasma AGP were found in ALM‐ or Saline‐treated pigs over the monitoring period. We conclude that the trauma of surgery alone was associated with significant increases in AGP in rats, compared to a contrasting decrease in pigs. Higher levels of plasma AGP in pigs prior to hemorrhagic shock is consistent with the higher ALM doses required to resuscitate pigs compared with rats.
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/AH09708
Abstract: Objective.To assess differences in perceived health-related quality of life among in iduals who are normal weight, overweight and obese in the general population, with particular emphasis on mental health. Method.A cross-sectional study was conducted among the general adult population in Queensland, Australia. Participants (n = 1212) were selected randomly for computer-assisted telephone interview in July 2007. The s le ranged between 18 and 93 years, with a mean age of 51.10 years (s.d. = 15.92). Demographic and physical and mental health (SF-12) data were collected. Self-reported height and weight were used to classify participants into three groups based on their body mass index: normal weight overweight obese. The associations between body mass index categories and SF-12 scores were investigated. Results.In this population s le, excess weight was associated with poorer physical health. In addition, significant associations were observed between excess weight and poor mental health for particular age groups. Obesity had a significant association with poor mental wellbeing for in iduals who are aged 45 to 54 years. No sex differences were observed. Conclusion.The results provide additional evidence of the relationship between excess weight and mental wellbeing and highlight the need for health professionals to be cognisant of the potential for in iduals who are obese to have a higher risk of experiencing mental health problems. What is known about the topic?The body mass index of the general population is rising steadily. Being overweight or obese has a detrimental effect on physical health and is a major cause of preventable death. However, there are conflicting findings regarding the implications of excess weight on an in iduals’ mental health. What does this paper add?This paper substantiates the relationship between body mass index and health-related quality of life in the general adult population. Obesity was associated with poor mental wellbeing for in iduals between the ages of 45 and 54. What are the implications for practice?This study underscores the need for mental health and wellbeing to become part of standard assessment practice for in iduals who are overweight or obese, particularly those aged between 45 and 54 years.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 08-2018
DOI: 10.1007/S00590-018-2280-1
Abstract: Accelerated rehabilitation protocols for medial opening wedge high tibial osteotomy (MOW HTO) using intraosseous implants have not previously been described. The present study provides early clinical and radiological outcomes of MOW HTO using a polyetheretherketone (PEEK) intraosseous system, in combination with an early weight-bearing protocol. Twenty consecutive knees (17 patients) underwent navigated MOW HTO using a PEEK implant with accelerated rehabilitation. Time to union and maintenance of correction were assessed radiographically for 12 months post-operative. Patient outcomes were monitored for a mean follow-up of 38 months (range 23-42) using standardised instruments (WOMAC, IKDC and Lysholm scores). All knees were corrected to valgus. The mean time to unassisted weight-bearing was 55 days (SD 24, range 21-106). Bone union occurred in 95% of knees by 6 months, with correction maintained for 15 knees at 12 months post-operative. Knees for which correction was lost within 1 year of surgery had significantly greater preoperative varus alignment. Implant survivorship was 95% and 80% at 12 and 38 months post-operative, respectively. Significant improvements in patient-reported satisfaction, knee function and return to daily activities from preoperative to 38 months post-operative were reported (WOMAC 36 v 0 IKDC 35.6 v 96 Lysholm 44.5 v 100). Accelerated rehabilitation following MOW HTO with an intraosseous PEEK implant did not delay bone union, with significantly improved functional outcomes within 3 months post-operative. Early findings suggest that this approach may be suitable for a defined patient subset, with consideration for the extent of preoperative genu varum.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.DIAGMICROBIO.2012.10.011
Abstract: Melioidosis is caused by the Gram-negative bacterium Burkholderia pseudomallei. The gold standard for diagnosis is culture, which requires at least 3-4 days to obtain a result, hindering successful treatment of acute disease. An indirect haemagglutination assay (IHA) is often used but lacks sensitivity. Approximately half of patients later confirmed culture positive are not detected by IHA at presentation and a subset of patients persistently continue to be IHA negative. More rapid and reliable serologic testing for melioidosis is essential and will improve diagnosis and patient outcome. We have developed an ELISA and a quantitative immuno-polymerase chain reaction assay capable of detecting melioidosis-specific antibodies and demonstrate their validity with IHA-negative sera from patients with melioidosis. These new sensitive assays are based upon a secreted antigenic fraction from B. pseudomallei and will be ideal for the diagnosis of melioidosis in patients in nonendemic regions returning from endemic tropical areas and for seroepidemiologic surveys.
Publisher: American Society for Microbiology
Date: 07-2002
DOI: 10.1128/IAI.70.7.3953-3958.2002
Abstract: Cytokine mRNA levels were assessed in Burkholderia pseudomallei -susceptible BALB/c mice and B. pseudomallei -resistant C57BL/6 mice following administration of a sublethal dose of less virulent (LV) B. pseudomallei , a candidate immunogen tested for protection against a highly virulent (HV) challenge. Compared on the basis of the bacterial loads, the cytokine patterns induced by HV and LV B. pseudomallei were similar, involving gamma interferon, interleukin-10, and other cytokines. Partial cross-protection between B. pseudomallei strains is shown to be associated with cytokine profiles involving both type 1 and type 2 cytokines.
Publisher: Public Library of Science (PLoS)
Date: 26-12-2019
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.NUCMEDBIO.2006.04.002
Abstract: (99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. S les were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.
Publisher: American Society for Microbiology
Date: 11-2007
DOI: 10.1128/CVI.00197-07
Abstract: The serological diagnosis of melioidosis is carried out using the indirect hemagglutination assay. We looked at the reactivity of sera from culture-proven cases of melioidosis from north Queensland against antigens derived from Burkholderia pseudomallei , B. thailandensis , and B. cepacia . Cross-reactivity between sera from culture-positive cases of melioidosis and B. thailandensis was demonstrated.
Location: Taiwan, Province of China
No related grants have been discovered for Jodie Morris.