National Indigenous Palliative Care Needs Study

This study involved extensive consultation with the community to identify the needs of Aboriginal and Torres Strait Islander peoples in palliative care

IMMUNE MODULATION OF THE MYCOBACTERIUM TUBERCULOSIS GRANULOMATOUS RESPONSE

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial cord factor trehalose-6’6-dimycolate (TDM) on granuloma formation. Investigations using knock-out mice suggest that TNF-a is involved in the initiation of the granulomatous response, complement factor C5a generates granuloma cohesiveness, and IL-6 is necessary for maintenance of an established granulomatous responses. Studies were next performed to determine the ability of lactoferrin to modulate the immune response and pathology to mycobacterial cord factor. Lactoferrin is an iron-binding glycoprotein with immunomodulatory properties that decrease tissue damage and promote Th1 responses. Mice challenged with TDM and treated with lactoferrin had decreased size and numbers of granulomas at the peak of the granulomatous response, accompanied by increased IL-10 and TGF-b production. Finally, the ability of lactoferrin to serve as a novel therapeutic for the treatment of TB was performed by aerosol challenging mice with MTB and treating them with lactoferrin added to the drinking water. Mice given tap water had lung log10 CFUs of 7.5 ± 0.3 at week 3 post-infection. Lung CFUs were significantly decreased in mice given lactoferrin starting the day of infection (6.4 ± 0.7) and mice started therapeutically on lactoferrin at day 7 after established infection (6.5 ± 0.4). Total lung inflammation in lactoferrin treated mice was significantly decreased, with fewer areas of macrophages, increased total lymphocytes, and increased numbers of CD4+ and CD8+ cells. The lungs of lactoferrin treated mice had increased CD4+ IFN-g+ cells and IL-17 producing cells on ELISpot analysis. It is hypothesized that lactoferrin decreases bacterial burden during MTB infection by early induction of Th1 responses

Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions

Blood oligosaccharides are attached to many proteins after translation, forming glycoproteins. Glycosylation refers to an enzyme-mediated modification that alters protein function, for example, their life span or their interactions with other proteins (1). By contrast, glycation refers to a monosaccharide (usually glucose) attaching nonenzymatically to the amino group of a protein. Glycated hemoglobin is formed by the condensation of glucose with select amino acid residues, commonly lysine, in hemoglobin to form an unstable Schiff base (aldimine, pre-HbA1c) (Fig. 1). The Schiff base may dissociate or may undergo an Amadori rearrangement to form a stable ketoamine. Figure 1 Formation of glycated protein. A reversible interaction between a primary amino group (depicted as NH2) of a protein and the carbonyl group of d-glucose yields a labile intermediate, called a Schiff base. This can undergo a slow and spontaneous Amadori rearrangement to form a stable ketoamine. HbA1c is formed if glucose attaches to the N-terminal valine of the β-chain of hemoglobin. If the glucose attaches to proteins in the plasma, fructosamine or glycated albumin results. RBC, red blood cell. Glycated hemoglobin, particularly HbA1c, has for decades been widely incorporated into the management (and, more recently, the diagnosis) of patients with diabetes. An important attribute is that glycation occurs continuously over the lifetime of the protein, so the concentration of the glycated protein reflects the average blood glucose value over a period of time. This contrasts with the measurement of blood glucose, which reveals the glucose concentration at the instant blood is sampled and which is acutely altered by multiple factors such as hormones, illness, food ingestion, and exercise (2). While HbA1c is by far the most extensively used—and studied—glycated protein (2–4), other glycated proteins that have been evaluated in clinical studies include fructosamine, glycated albumin, and

Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P < .05). Cavities contained significantly more T-regulatory cells (14.8%) than found in lipid pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis

Lactoferrin Augmentation of the BCG Vaccine Leads to Increased Pulmonary Integrity

The goal of vaccination to prevent tuberculosis disease (TB) is to offer long-term protection to the individual and the community. In addition, the success of any protective TB vaccine should include the ability to limit cavitary formation and disease progression. The current BCG vaccine protects against disseminated TB disease in children by promoting development of antigenic-specific responses. However, its efficacy is limited in preventing postprimary pulmonary disease in adults that is responsible for the majority of disease and transmission. This paper illustrates the use of lactoferrin as an adjuvant to boost efficacy of the BCG vaccine to control organism growth and limit severe manifestation of pulmonary disease. This resulting limitation in pathology may ultimately, limit spread of bacilli and subsequent transmission of organisms between individuals. The current literature is reviewed, and data is presented to support molecular mechanisms underlying lactoferrin's utility as an adjuvant for the BCG vaccine

Lactoferrin Augmentation of the BCG Vaccine Leads to Increased Pulmonary Integrity

The goal of vaccination to prevent tuberculosis disease (TB) is to offer long-term protection to the individual and the community. In addition, the success of any protective TB vaccine should include the ability to limit cavitary formation and disease progression. The current BCG vaccine protects against disseminated TB disease in children by promoting development of antigenic-specific responses. However, its efficacy is limited in preventing postprimary pulmonary disease in adults that is responsible for the majority of disease and transmission. This paper illustrates the use of lactoferrin as an adjuvant to boost efficacy of the BCG vaccine to control organism growth and limit severe manifestation of pulmonary disease. This resulting limitation in pathology may ultimately, limit spread of bacilli and subsequent transmission of organisms between individuals. The current literature is reviewed, and data is presented to support molecular mechanisms underlying lactoferrin&apos;s utility as an adjuvant for the BCG vaccine

Enhancing the Behaviour Change Wheel with synthesis, stakeholder involvement and decision-making: a case example using the 'Enhancing the Quality of Psychological Interventions Delivered by Telephone' (EQUITy) research programme.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-14Publication status: PublishedFunder: Programme Grants for Applied Research; Grant(s): RP-PG-1016-20010BackgroundUsing frameworks such as the Behaviour Change Wheel to develop behaviour change interventions can be challenging because judgement is needed at various points in the process and it is not always clear how uncertainties can be resolved. We propose a transparent and systematic three-phase process to transition from a research evidence base to a behaviour change intervention. The three phases entail evidence synthesis, stakeholder involvement and decision-making. We present the systematic development of an intervention to enhance the quality of psychological treatment delivered by telephone, as a worked example of this process.MethodIn phase 1 (evidence synthesis), we propose that the capabilities (C), opportunities (O) and motivations (M) model of behaviour change (COM-B) can be used to support the synthesis of a varied corpus of empirical evidence and to identify domains to be included in a proposed behaviour change intervention. In phase 2 (stakeholder involvement), we propose that formal consensus procedures (e.g. the RAND Health/University of California-Los Angeles Appropriateness Methodology) can be used to facilitate discussions of proposed domains with stakeholder groups. In phase 3 (decision-making), we propose that behavioural scientists identify (with public/patient input) intervention functions and behaviour change techniques using the acceptability, practicability, effectiveness/cost-effectiveness, affordability, safety/side-effects and equity (APEASE) criteria.ResultsThe COM-B model was a useful tool that allowed a multidisciplinary research team, many of whom had no prior knowledge of behavioural science, to synthesise effectively a varied corpus of evidence (phase 1: evidence synthesis). The RAND Health/University of California-Los Angeles Appropriateness Methodology provided a transparent means of involving stakeholders (patients, practitioners and key informants in the present example), a structured way in which they could identify which of 93 domains identified in phase 1 were essential for inclusion in the intervention (phase 2: stakeholder involvement). Phase 3 (decision-making) was able to draw on existing Behaviour Change Wheel resources to revisit phases 1 and 2 and facilitate agreement among behavioural scientists on the final intervention modules. Behaviour changes were required at service, practitioner, patient and community levels.ConclusionFrameworks offer a foundation for intervention development but require additional elucidation at each stage of the process. The decisions adopted in this study are designed to provide an example on how to resolve challenges while designing a behaviour change intervention. We propose a three-phase process, which represents a transparent and systematic framework for developing behaviour change interventions in any setting

Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals.

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 ( Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement