Climate Variability, Social and Environmental Factors, and Ross River Virus Transmission: Research Development and Future Research Needs

Background: Arbovirus diseases have emerged as a global public health concern. However, the impact of climatic, social and environmental variability on the transmission of arbovirus diseases remains to be determined. Objective: We provided an overview of research development and future research directions about the inter-relationship between climate variability, social and environmental factors and the transmission of Ross River virus (RRV) – the most common and widespread arbovirus disease in Australia. Methods: We conducted a systematic literature search on climatic, social and environmental factors and RRV disease. Potentially relevant studies were identified from a series of electronic searches. Databases searched were the MEDLINE (via EBSCOhost), Current Contents Connect (via ISI Web of Knowledge) and ScienceDirect. We critically reviewed key predictors of RRV transmission through an integration of our own research with literature. Results: The body of evidence reveals that the transmission cycles of RRV disease appeared to be sensitive to climate variability. Rainfall, temperature and high tides were among major determinants of the transmission of RRV disease at macro level. However, the nature and magnitude of the inter-relationship between climate variability, mosquito density and the transmission of RRV disease varied with geographic area and socio-environmental condition. Projected anthropogenic global climatic change may result in an increase in RRV infections. Conclusions: The analysis indicates that there is a complex relationship between climate variability, social and environmental factors and Ross River virus transmission. Different strategies should be adopted for the control and prevention of Ross River virus disease at different levels. These research findings could be used as an additional tool to support decision-making in disease control/surveillance and risk management

Assessing psychological flexibility in test situations: The test anxiety acceptance and action questionnaire for adolescents

Acceptance-based interventions such as acceptance and commitment therapy motivated the development of measures of psychological flexibility. As an anxiety-based condition, test anxiety can be conceptualized as an experiential avoidance condition. Given the need to evaluate acceptance and action processes in test anxiety and the lack of such an instrument, the present study aimed to explore the factor structure and psychometric properties of the Test Anxiety-Acceptance and Action Questionnaire for Adolescents (TA-AAQ-A), adapted from the Social Anxiety-Acceptance and Action Questionnaire. The sample comprised 827 adolescents (12-18 years old) from 10 Portuguese schools. Confirmatory factor analysis indicated a well-adjusted 12-item single-factor measure, invariant across genders. Results also showed high internal consistency and temporal stability, and good convergent validity. Findings suggest the TA-AAQ-A is a reliable and valid measure for the assessment of adolescents' psychological flexibility in test situations

Determinants of Functional Coupling between Astrocytes and Respiratory Neurons in the Pre-Bötzinger Complex

Respiratory neuronal network activity is thought to require efficient functioning of astrocytes. Here, we analyzed neuron-astrocyte communication in the pre-Bötzinger Complex (preBötC) of rhythmic slice preparations from neonatal mice. In astrocytes that exhibited rhythmic potassium fluxes and glutamate transporter currents, we did not find a translation of respiratory neuronal activity into phase-locked astroglial calcium signals. In up to 20% of astrocytes, 2-photon calcium imaging revealed spontaneous calcium fluctuations, although with no correlation to neuronal activity. Calcium signals could be elicited in preBötC astrocytes by metabotropic glutamate receptor activation or after inhibition of glial glutamate uptake. In the latter case, astrocyte calcium elevation preceded a surge of respiratory neuron discharge activity followed by network failure. We conclude that astrocytes do not exhibit respiratory-rhythmic calcium fluctuations when they are able to prevent synaptic glutamate accumulation. Calcium signaling is, however, observed when glutamate transport processes in astrocytes are suppressed or neuronal discharge activity is excessive

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and beta-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated beta-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assay

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Power grip, pinch grip, manual muscle testing or thenar atrophy - which should be assessed as a motor outcome after carpal tunnel decompression? A systematic review

<p>Abstract</p> <p>Background</p> <p>Objective assessment of motor function is frequently used to evaluate outcome after surgical treatment of carpal tunnel syndrome (CTS). However a range of outcome measures are used and there appears to be no consensus on which measure of motor function effectively captures change. The purpose of this systematic review was to identify the methods used to assess motor function in randomized controlled trials of surgical interventions for CTS. A secondary aim was to evaluate which instruments reflect clinical change and are psychometrically robust.</p> <p>Methods</p> <p>The bibliographic databases Medline, AMED and CINAHL were searched for randomized controlled trials of surgical interventions for CTS. Data on instruments used, methods of assessment and results of tests of motor function was extracted by two independent reviewers.</p> <p>Results</p> <p>Twenty-two studies were retrieved which included performance based assessments of motor function. Nineteen studies assessed power grip dynamometry, fourteen studies used both power and pinch grip dynamometry, eight used manual muscle testing and five assessed the presence or absence of thenar atrophy. Several studies used multiple tests of motor function. Two studies included both power and pinch strength and reported descriptive statistics enabling calculation of effect sizes to compare the relative responsiveness of grip and pinch strength within study samples. The study findings suggest that tip pinch is more responsive than lateral pinch or power grip up to 12 weeks following surgery for CTS.</p> <p>Conclusion</p> <p>Although used most frequently and known to be reliable, power and key pinch dynamometry are not the most valid or responsive tools for assessing motor outcome up to 12 weeks following surgery for CTS. Tip pinch dynamometry more specifically targets the thenar musculature and appears to be more responsive. Manual muscle testing, which in theory is most specific to the thenar musculature, may be more sensitive if assessed using a hand held dynamometer – the Rotterdam Intrinsic Handheld Myometer. However further research is needed to evaluate its reliability and responsiveness and establish the most efficient and psychometrically robust method of evaluating motor function following surgery for CTS.</p

Adenosine and lymphocyte regulation

Adenosine is a potent extracellular messenger that is produced in high concentrations under metabolically unfavourable conditions. Tissue hypoxia, consequent to a compromised cellular energy status, is followed by the enhanced breakdown of ATP leading to the release of adenosine. Through the interaction with A2 and A3 membrane receptors, adenosine is devoted to the restoration of tissue homeostasis, acting as a retaliatory metabolite. Several aspects of the immune response have to be taken into consideration and even though in general it is very important to dampen inflammation, in some circumstances, such as the case of cancer, it is also necessary to increase the activity of immune cells against pathogens. Therefore, adenosine receptors that are defined as ‘sensors–of metabolic changes in the local tissue environment may be very important targets for modulation of immune responses and drugs devoted to regulating the adenosinergic system are promising in different clinical situations

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Forest Plant and Bird Communities in the Lau Group, Fiji

We examined species composition of forest and bird communities in relation to environmental and human disturbance gradients on Lakeba (55.9 km²), Nayau (18.4 km²), and Aiwa Levu (1.2 km²), islands in the Lau Group of Fiji, West Polynesia. The unique avifauna of West Polynesia (Fiji, Tonga, Samoa) has been subjected to prehistoric human-caused extinctions but little was previously known about this topic in the Lau Group. We expected that the degree of human disturbance would be a strong determinant of tree species composition and habitat quality for surviving landbirds, while island area would be unrelated to bird diversity.All trees > 5 cm diameter were measured and identified in 23 forest plots of 500 m² each. We recognized four forest species assemblages differentiated by composition and structure: coastal forest, dominated by widely distributed species, and three forest types with differences related more to disturbance history (stages of secondary succession following clearing or selective logging) than to environmental gradients (elevation, slope, rockiness). Our point counts (73 locations in 1 or 2 seasons) recorded 18 of the 24 species of landbirds that exist on the three islands. The relative abundance and species richness of birds were greatest in the forested habitats least disturbed by people. These differences were due mostly to increased numbers of columbid frugivores and passerine insectivores in forests on Lakeba and Aiwa Levu. Considering only forested habitats, the relative abundance and species richness of birds were greater on the small but completely forested (and uninhabited) island of Aiwa Levu than on the much larger island of Lakeba.Forest disturbance history is more important than island area in structuring both tree and landbird communities on remote Pacific islands. Even very small islands may be suitable for conservation reserves if they are protected from human disturbance