Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

OBJECTIVE: To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance.

DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes.

MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic-hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry.

RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P=0.022) and central abdominal fat mass (P=0.034), and with blood glucose concentration in non-obese subjects (P=0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P=0.013) and insulin (P=0.034), and with body fat mass (P=0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P=0.009) and energy expenditure (P=0.013).

CONCLUSION/INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

Cancer patient preferences for communication of prognosis in the metastatic setting

PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.

Nutrient intake and plate waste from an Australian residential care facility

Objective: To determine the plate waste, energy and selected-nutrient intake, from elderly residents living in a high-level care (HLC) and low-level care (LLC) facility.

Design: Three, single, whole day assessments of plate waste, energy, and selected nutrients, using a visual rating plate waste scale.

Setting: Long-term residential care establishment.

Subjects: One hundred and sixty-nine (93 HLC and 76 LLC) individual daily intakes.

Main findings: The mean energy wasted throughout the whole day was 17%. The energy wasted from main meals (16%) was significantly less than the energy wasted at mid-meals (22%, P=0.049). The lowest mean energy wastage occurred at breakfast (8%) compared to lunch (22%) and dinner (25%, P<0.001). The mean (s.d.) daily energy served and consumed was 8.1 (2.0) and 6.6 (2.2) MJ, respectively. There was no difference in energy served or consumed between HLC and LLC residents. On the observation day, 60% of residents consumed less than their estimated energy requirement. The mean calcium intake was 796 (346) mg, and the median (inter-quartile range) vitamin D intake was 1.78 (2.05) μg.

Conclusion: On 1 day, more than half the residents surveyed were at risk of consuming an inadequate energy intake, which over-time, may result in body weight loss. Although wastage was not excessive and energy served was adequate, the amount of food eaten was insufficient to meet energy and calcium requirements for a significant number of residents and it is not possible to consume sufficient vitamin D through food sources.

A novel zebrafish jak2a V581F model shared features of human JAK2 V617F polycythemia vera

Objective : The Janus kinase 2 (JAK2) is important for embryonic primitive hematopoiesis. A gain-of-function JAK2 (JAK2^V617F) mutation in human is pathogenetically linked to polycythemia vera (PV). In this study, we generated a zebrafish ortholog of human JAK2^V617F (referred herewith jak2a^V581F) by site-directed mutagenesis and examined its relevance as a model of human PV.

Materials and Methods : Zebrafish embryos at one-cell stage were injected with jak2a^V581F mRNA (200pg/embryo). In some experiments, the embryos were treated with a specific JAK2 inhibitor, TG101209. The effects of jak2a stimulation on hematopoiesis, jak/stat signaling, and erythropoietin signaling were evaluated at 18-somites.

Results : Injection with jak2a^V581F mRNA significantly increased erythropoiesis, as enumerated by flow cytometry based on gfp+ population in dissociated Tg(gata1:gfp) embryos. The response was reduced by stat5.1 morpholino coinjection (control: 4.37% ± 0.08%; jak2a^V581F injected: 5.71% ± 0.07%, coinjecting jak2a^V581F mRNA and stat5.1 morpholino: 4.66% ± 0.13%; p < 0.01). jak2a^V581F mRNA also upregulated gata1 (1.83 ± 0.08 fold; p = 0.005), embryonic α-hemoglobin (1.61 ± 0.12 fold; p = 0.049), and β-hemoglobin gene expression (1.65 ± 0.13–fold; p = 0.026) and increased stat5 phosphorylation. These responses were also ameliorated by stat5.1 morpholino coinjection or treatment with a specific JAK2 inhibitor, TG101209. jak2a^V581F mRNA significantly reduced erythropoietin gene (0.24 ± 0.03 fold; p = 0.006) and protein expression (control: 0.633 ± 0.11; jak2a^V581F mRNA: 0.222 ± 0.07 mIU/mL; p = 0.019).

Conclusion : The zebrafish jak2a^V581F model shared many features with human PV and might provide us with mechanistic insights of this disease.

The effect of surface and hydrodynamic forces on the shape of a fluid drop approaching a solid surface

This paper describes an experiment designed to measure surface and hydrodynamic forces between a mercury drop and a flat mica surface immersed in an aqueous medium. An optical interference technique allows measurement of the shape of the mercury drop as well as its distance from the mica, for various conditions of applied potential, applied pressure, and solution conditions. This enables a detailed exploration of the surface forces, particularly double-layer forces, between mercury and mica. A theoretical analysis of drop shape under the influence of surface forces shows that deformation of the drop is a sensitive indicator of the forces, as well as being a very important factor in establishing the overall interaction between the solid and the fluid.

The impact of climate variability and change on cryptosporidiosis and giardiasis rates in New Zealand

Aim: To investigate the spatial relationship between climate variability and cryptosporidiosis and giardiasis notifications in New Zealand between 1997 and 2006.

Methods: Negative binomial regression was used to analyse spatial relationships between cryptosporidiosis and giardiasis notifications in New Zealand between 1997 and 2006, and climatological average rainfall and temperature at the Census Area Unit (CAU) level. The quality of domestic water supplies, urban-rural status and deprivation were included as covariates.

Main results: Giardiasis: There was a positive association between rainfall and giardiasis and between temperature and giardiasis.

Cryptosporidiosis: There was a positive association between rainfall and cryptosporidiosis and a negative association between temperature and cryptosporidiosis. The effect of rainfall was modified by the quality of the domestic water supply.

Conclusions: These findings suggest that climate variability affects protozoan disease rates in New Zealand. However, predicting the effect of climate change from this study is difficult, as these results suggest that the projected increases in temperature and rainfall may have opposing effects on cryptosporidiosis rates. Nevertheless, water supply quality appeared to modify the impact of increased rainfall on cryptosporidiosis rates. This finding suggests that improving water supply quality in New Zealand could reduce vulnerability to the impact of climate change on protozoan diseases.

TMS stimulus-response asymmetry in left- and right handed individuals

There have been inconsistencies in the literature regarding asymmetrical neural control and results of experiments using TMS techniques. Therefore, the aim of this study was to further our understanding of the neural relationships that may underlie performance asymmetry with respect to the distal muscles of the hand using a TMS stimulus–response curve technique. Twenty-four male subjects (12 right handed, 12 left handed) participated in a TMS stimulus–response (S–R) curve trial. Focal TMS was applied over the motor cortex to find the optimal position for the first dorsal interossei muscle and to determine rest threshold (RTh). Seven TMS intensities ranging from 90 to 150 % of RTh were delivered in 10 % increments. One single TMS block consisted of 16 stimuli at each intensity. Peak-to-peak amplitudes were measured and the S–R curve generated. In right-handed subjects, the mean difference in slopes between the right and left hand was −0.011 ± 0.03, while the mean difference between hands in left-handed subjects was −0.049 ± 0.08. Left-handed normalized data in right handers displayed a mean of 1.616 ± 1.019 (two-tailed t test p < 0.05). The left-handed group showed a significant change in the normalized slope as indicated by a mean of 1.693 ± 0.149 (two-tailed t test p < 0.00006). The results found in this study reinforce previous work which suggests that there is an asymmetry in neural drive that exists in both left- and right-handed individuals. However, the results show that the non-dominant motor hemisphere displays a greater amount of excitability than the dominant, which goes against the conventional dogma. This asymmetry indicates that the non-dominant hemisphere may have a higher level of excitation or a lower level of inhibition for both groups of participants.

Leadership and teamwork in medical emergencies: performance of nursing students and registered nurses in simulated patient scenarios

Aims and objectives: To examine nursing students' and registered nurses' teamwork skills whilst managing simulated deteriorating patients. Background: Studies continue to show the lack of timely recognition of patient deterioration. Management of deteriorating patients can be influenced by education and experience. Design: Mixed methods study conducted in two universities and a rural hospital in Victoria, and one university in Queensland, Australia. Methods: Three simulation scenarios (chest pain, hypovolaemic shock and respiratory distress) were completed in teams of three by 97 nursing students and 44 registered nurses, equating to a total of 32 student and 15 registered nurse teams. Data were obtained from (1) Objective Structured Clinical Examination rating to assess performance; (2) Team Emergency Assessment Measure scores to assess teamwork; (3) simulation video footage; (4) reflective interview during participants' review of video footage. Qualitative thematic analysis of video and interview data was undertaken. Results: Objective structured clinical examination performance was similar across registered nurses and students (mean 54% and 49%); however, Team Emergency Assessment Measure scores differed significantly between the two groups (57% vs 38%, t = 6·841, p < 0·01). In both groups, there was a correlation between technical (Objective Structured Clinical Examination) and nontechnical (Team Emergency Assessment Measure) scores for the respiratory distress scenario (student teams: r = 0·530, p = 0·004, registered nurse teams r = 0·903, p < 0·01) and hypovolaemia scenario (student teams: r = 0·534, p = 0·02, registered nurse teams: r = 0·535, p = 0·049). Themes generated from the analysis of the combined quantitative and qualitative data were as follows: (1) leadership and followership behaviours; (2) help-seeking behaviours; (3) reliance on previous experience; (4) fixation on a single detail; and (5) team support. Conclusions: There is scope to improve leadership, team work and task management skills for registered nurses and nursing students. Simulation appears to be beneficial in enabling less experienced staff to assess their teamwork skills. Relevance to clinical practice: There is a need to encourage less experienced staff to become leaders and for all staff to develop improved teamwork skills for medical emergencies. © 2014 John Wiley & Sons Ltd.

Plantations, not farmlands, cause biotic homogenisation of ground-active beetles in South-Eastern Australia

Following landscape change, species invasions and extinctions may lead to biotic homogenisation, resulting in increased taxonomic and functional similarity between previously distinct biotas. Biotic homogenisation is more likely to occur in landscapes where the matrix contrasts strongly with native vegetation patches. To test this, we examined the distribution of ground-active beetles in a landscape of remnant Eucalyptus open woodland patches where large areas of lower contrast matrix (farmland) are being transformed to high-contrast pine plantations in south-eastern Australia. We sampled beetles from 30 sites including six replicates of five categories; (1) remnants adjacent to farmland, (2) remnants adjacent to plantation, (3) farmland, (4) plantation, and, (5) remnants between pine plantation and farmland. Community composition in the pine matrix was similar to native patches embedded in pine (ANOSIM, Global R=. 0.49, P<. 0.000), which we suggest is due to biotic homogenisation. Remnant patches with edges of both farmland and pine plantation did not represent an intermediate community composition between patches surrounded by either matrix type, but rather a unique habitat with unique species. Farmland supported the greatest number of individuals (. F=. 9.049, df. =. 25, P<. 0.000) and species (. F=. 5.875, df. =. 25, P=. 0.002), even compared to native remnant patches. Our results suggest that matrix transformations can reduce species richness and homogenise within-patch populations. This may increase the risk of species declines in fragmented landscapes where plantations are not only replacing native vegetation patches, but also other matrix types that may better support biodiversity. Our findings are particularly concerning given expanding plantation establishment worldwide.

Leadership and teamwork in medical emergencies: Performance of nursing students and registered nurses in simulated patient scenarios

Aims and objectives: To examine nursing students' and registered nurses' teamwork skills whilst managing simulated deteriorating patients. Background: Studies continue to show the lack of timely recognition of patient deterioration. Management of deteriorating patients can be influenced by education and experience. Design: Mixed methods study conducted in two universities and a rural hospital in Victoria, and one university in Queensland, Australia. Methods: Three simulation scenarios (chest pain, hypovolaemic shock and respiratory distress) were completed in teams of three by 97 nursing students and 44 registered nurses, equating to a total of 32 student and 15 registered nurse teams. Data were obtained from (1) Objective Structured Clinical Examination rating to assess performance; (2) Team Emergency Assessment Measure scores to assess teamwork; (3) simulation video footage; (4) reflective interview during participants' review of video footage. Qualitative thematic analysis of video and interview data was undertaken. Results: Objective structured clinical examination performance was similar across registered nurses and students (mean 54% and 49%); however, Team Emergency Assessment Measure scores differed significantly between the two groups (57% vs 38%, t = 6·841, p < 0·01). In both groups, there was a correlation between technical (Objective Structured Clinical Examination) and nontechnical (Team Emergency Assessment Measure) scores for the respiratory distress scenario (student teams: r = 0·530, p = 0·004, registered nurse teams r = 0·903, p < 0·01) and hypovolaemia scenario (student teams: r = 0·534, p = 0·02, registered nurse teams: r = 0·535, p = 0·049). Themes generated from the analysis of the combined quantitative and qualitative data were as follows: (1) leadership and followership behaviours; (2) help-seeking behaviours; (3) reliance on previous experience; (4) fixation on a single detail; and (5) team support. Conclusions: There is scope to improve leadership, team work and task management skills for registered nurses and nursing students. Simulation appears to be beneficial in enabling less experienced staff to assess their teamwork skills. Relevance to clinical practice: There is a need to encourage less experienced staff to become leaders and for all staff to develop improved teamwork skills for medical emergencies.

Milled non-mulberry silk fibroin microparticles as biomaterial for biomedical applications

Silk fibroin has been widely employed in various forms as biomaterials for biomedical applications due to its superb biocompatibility and tunable degradation and mechanical properties. Herein, silk fibroin microparticles of non-mulberry silkworm species (Antheraea assamensis, Antheraea mylitta and Philosamia ricini) were fabricated via a top-down approach using a combination of wet-milling and spray drying techniques. Microparticles of mulberry silkworm (Bombyx mori) were also utilized for comparative studies. The fabricated microparticles were physico-chemically characterized for size, stability, morphology, chemical composition and thermal properties. The silk fibroin microparticles of all species were porous (∼5μm in size) and showed nearly spherical morphology with rough surface as revealed from dynamic light scattering and microscopic studies. Non-mulberry silk microparticles maintained the typical silk-II structure with β-sheet secondary conformation with higher thermal stability. Additionally, non-mulberry silk fibroin microparticles supported enhanced cell adhesion, spreading and viability of mouse fibroblasts than mulberry silk fibroin microparticles (p<0.001) as evidenced from fluorescence microscopy and cytotoxicity studies. Furthermore, in vitro drug release from the microparticles showed a significantly sustained release over 3 weeks. Taken together, this study demonstrates promising attributes of non-mulberry silk fibroin microparticles as a potential drug delivery vehicle/micro carrier for diverse biomedical applications.

Global brachiopod palaeobiogeographical evolution from Changhsingian (Late Permian) to Rhaetian (Late Triassic)

Previous studies suggest that the end-Permian mass extinction caused a dramatic drop of marine biodiversity near the Permian-Triassic boundary. However, it is unclear how profoundly this severe extinction might have changed the global provincialism, and how global provincialism responded to the protracted process of this extinction and subsequent recovery through the Triassic. In this paper, we carried out quantitative time-series analyses of global brachiopod palaeobiogeography over a timespan of nine consecutive stages/substages from the latest Permian Changhsingian to the latest Triassic Rhaetian based on a global brachiopod database of 483 genera and 2459 species from 1425 localities. Our results suggest that the extinction resulted in a global 'biogeographical eclipse' in the ensuing Early Triassic Griesbachian and Dienerian times in that neither biogeographic realm nor province could be recognized. It was characterized by an extreme low-diversity, mostly dwarfed and nearly globally distributed brachiopod fauna, coupled with persistently high sea surface temperature and a flattened global latitudinal thermal gradient. Global provincialization emerged again during the Olenekian at province level and reached its peak stage during the Carnian when three realms and six provinces were clearly recognized. Global provincialism became weakened again in the latest Triassic Rhaetian, marked by three general realms, but no province distinguished. Our analyses suggest that both palaeolatitude-related thermal gradient and the presence of Pangea (a profound geographic barrier) were most effective in explaining the spatial patterns. In addition, oceanic currents along the northwestern coast of Pangea also played an important (albeit regional) role in linking southern North and Central America brachiopod faunas with those of the Boreal Realm. This study also revealed that the brachiopod biodiversity center moved northwards over the studied interval, accompanied and hence accountable for by the northward drift of a large number of tectonic blocks in the Palaeotethys and Neotethys during the Triassic.