How do I sound to me? Perceived changes in communication in Parkinson's disease

Objective: To examine self and carer perceived changes in communication associated with Parkinson's disease and relate these to speech intelligibility, gender, age and other disease measures. Design: Cross-sectional survey of a hospital- and community-based sample of 176 people with Parkinson's disease and their carers using a questionnaire based on semantic differential techniques. Participants: One hundred and four people with Parkinson's disease with no history of communication difficulties prior to onset of their Parkinson's disease and 45 primary carers who returned completed questionnaires. Main outcome measures: Differences in ratings for `before' the onset of Parkinson's disease versus present status. Results: There was a strong perception of negative impact on communication between `before' and `now', irrespective of age and gender and largely independent of disease severity and duration, intelligibility and cognitive status. Activities of daily living (assessed by Unified Parkinson's Disease Rating Scale (UPDRS) II) and depression rating scale scores had the strongest association with change (adjusted R 2 0.27). There was a significant correlation between the rank order of perceived change in features examined in people with Parkinson's disease versus their carers, though in general carers rated change as having less impact. Conclusions: Parkinson's disease exercises a strong influence on communication even before apparent alterations to intelligibility or motor status

The Next Generation of Science Educators: Museum Volunteers

There is a growing need for science educators and communicators who can support public understanding of complex science issues. Furthermore, little is known about how to nurture career aspirations for teaching science. This study examined the influence of youth volunteer experiences on career aspirations through a lens of science identity. Twenty-one participants were interviewed about high school volunteer experiences at a science museum. Data were coded for factors related to science identity (recognition, competence, and performance) and career aspirations. Results showed that the museum program contributed to the development of youth volunteers’ science identities through experiences that bolstered individuals’ science recognition, science competence, and science performance. Further analyses revealed the program’s impact on the development of individuals’ career interests in the areas of science communication and teaching. The results showed that after participating in the volunteer program, individuals indicated increased interests in communicating science to the public, teaching in informal science settings, and teaching in K-12 settings. These findings suggest that museum volunteer programs with an explicit focus on communicating science to the public may be optimal places to cultivate the next generation of science educators and communicators

Sampling re-design increases power to detect change in the Great Barrier Reef’s inshore water quality

Monitoring programs are fundamental to understanding the state and trend of aquatic ecosystems. Sampling designs are a crucial component of monitoring programs and ensure that measurements evaluate progress toward clearly stated management objectives, which provides a mechanism for adaptive management. Here, we use a well-established marine monitoring program for inshore water quality in the Great Barrier Reef (GBR), Australia to investigate whether a sampling re-design has increased the program’s capacity to meet its primary objectives. Specifically, we use bootstrap resampling to assess the change in statistical power to detect temporal water quality trends in a 15-year inshore marine water quality data set that includes data from both before and after the sampling re-design. We perform a comprehensive power analysis for six water quality analytes at four separate study areas in the GBR Marine Park and find that the sampling re-design (i) increased power to detect trends in 23 of the 24 analyte-study area combinations, and (ii) resulted in an average increase in power of 34% to detect increasing or decreasing trends in water quality analytes. This increase in power is attributed more to the addition of sampling locations than increasing the sampling rate. Therefore, the sampling re-design has substantially increased the capacity of the program to detect temporal trends in inshore marine water quality. Further improvements in sampling design need to focus on the program’s capability to reliably detect trends within realistic timeframes where inshore improvements to water quality can be expected to occur

The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β

The transcription factor BMAL1 is a clock protein that generates daily or circadian rhythms in physiological functions including the inflammatory response of macrophages. Intracellular metabolic pathways direct the macrophage inflammatory response, however whether the clock is impacting intracellular metabolism to direct this response is unclear. Specific metabolic reprogramming of macrophages controls the production of the potent pro-inflammatory cytokine IL-1β. We now describe that the macrophage molecular clock, through Bmal1, regulates the uptake of glucose, its flux through glycolysis and the Krebs cycle, including the production of the metabolite succinate to drive Il-1β production. We further demonstrate that BMAL1 modulates the level and localisation of the glycolytic enzyme PKM2, which in turn activates STAT3 to further drive Il-1β mRNA expression. Overall, this work demonstrates that BMAL1 is a key metabolic sensor in macrophages, and its deficiency leads to a metabolic shift of enhanced glycolysis and mitochondrial respiration, leading to a heightened pro-inflammatory state. These data provide insight into the control of macrophage driven inflammation by the molecular clock, and the potential for time-based therapeutics against a range of chronic inflammatory diseases

Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

International Public Health Research Involving Interpreters: a Case Study from Bangladesh

Background: Cross-cultural and international research are important components of public health research, but the challenges of language barriers and working with interpreters are often overlooked, particularly in the case of qualitative research. Methods: A case-study approach was used to explore experiences of working with an interpreter in Bangladesh as part of a research project investigating women's experiences of emergency obstetric care. The case study: Data from the researcher's field notes provided evidence of experiences in working with an interpreter and show how the model of interviewing was adapted over time to give a more active role to the interpreter. The advantages of a more active role were increased rapport and "flow" in interviews. The disadvantages included reduced control from the researcher's perspective. Some tensions between the researcher and interpreter remained hard to overcome, irrespective of the model used. Independent transcription and translation of the interviews also raised questions around accuracy in translation. Conclusion: The issues examined in this case study have broader implications for public health research. Further work is needed in three areas: 1) developing effective relationships with interpreters; 2) the impact of the interpreter on the research process; and 3) the accuracy of the translation and level of analysis needed in any specific public health research. Finally, this paper highlights the importance to authors of reflecting on the potential impact of translation and interpretation on the research process when disseminating their research

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.<p></p> Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.<p></p> Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.<p></p> Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.<p></p&gt