Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis

ImportanceSudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality.ObjectiveTo estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients.ResultsIn the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50 000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT.

Conclusion and Relevance

In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.     

Health and Masculinities Shaped by Agency within Structures among Young Unemployed Men in a Northern Swedish Context

AimThe aim of our paper was to explore expressions of life choices and life chances (aspects of agency within structures) related to power and experiences of health among early unemployed adolescent young men during the transition period to adulthood. These expressions of agency within structure were interpreted in the light of Cockerham’s Health Lifestyles Theory. Furthermore, social constructions of masculinities were addressed in our analysis.MethodsRepeated interviews with ten young men in a cohort of school leavers were analyzed with qualitative content analysis.ConclusionsQualitative research could contribute to develop the understanding of the agency within structure relationships. Future studies need to pay attention to experiences of health among young people at the margin of the labor market in various milieus – and to analyze these in relation to gender constructions and within the frame-work of agency within structure.     

Drought‐stress and plant resistance affect herbivore performance and proteome: the case of the green peach aphid Myzus persicae (Hemiptera: Aphididae)

Little is known about the simultaneous effects of drought stress and plant resistance on herbivorous insects. By subjecting the green peach aphid Myzus persicae Sulzer to well‐watered and drought‐stressed plants of both susceptible and resistant peach (Prunus persica), the effects of both stressors on aphid performance and proteomics are tested. Overall, the influence of the water treatment on aphid performance is less pronounced than the effect of host plant genetic resistance. On the susceptible cultivar, aphid survival, host acceptance and ability to colonize the plant do not depend on water treatment. On the resistant cultivar, aphid survival and ability to colonize are higher on drought‐stressed than on well‐watered plants. A study examining the pattern of protein expression aiming to explain the variation in aphid performance finds higher protein expression in aphids on the drought‐stressed susceptible cultivars compared with the well‐watered ones. In the susceptible cultivar, the regulated proteins are related to energy metabolism and exoskeleton functionality, whereas, in the resistant cultivar, the proteins are involved with the cytoskeleton. Comparison of the protein expression ratios for resistant versus susceptible plants reveals that four proteins are down‐regulated in well‐watered plants and 15 proteins are down‐regulated in drought‐stressed plants. Drought stress applied to the susceptible cultivar induces the regulation of proteins in M. persicae that enable physiological adaptation to maintain an almost unaltered aphid performance. By contrast, for aphids on the resistant cultivar subjected to drought stress, the down‐regulation of proteins responds to an induced host susceptibility effect.     

αII-Spectrin Regulates Invadosome Stability and Extracellular Matrix Degradation

Invadosomes are actin-rich adhesion structures involved in tissue invasion and extracellular matrix (ECM) remodelling. αII-Spectrin, an ubiquitous scaffolding component of the membrane skeleton and a partner of actin regulators (ABI1, VASP and WASL), accumulates highly and specifically in the invadosomes of multiple cell types, such as mouse embryonic fibroblasts (MEFs) expressing SrcY527F, the constitutively active form of Src or activated HMEC-1 endothelial cells. FRAP and live-imaging analysis revealed that αII-spectrin is a highly dynamic component of invadosomes as actin present in the structures core. Knockdown of αII-spectrin expression destabilizes invadosomes and reduces the ability of the remaining invadosomes to digest the ECM and to promote invasion. The ECM degradation defect observed in spectrin-depleted-cells is associated with highly dynamic and unstable invadosome rings. Moreover, FRAP measurement showed the specific involvement of αII-spectrin in the regulation of the mobile/immobile β3-integrin ratio in invadosomes. Our findings suggest that spectrin could regulate invadosome function and maturation by modulating integrin mobility in the membrane, allowing the normal processes of adhesion, invasion and matrix degradation. Altogether, these data highlight a new function for spectrins in the stability of invadosomes and the coupling between actin regulation and ECM degradation.     

A Nuclear Marker for Mammalian Cells and Its Use with Intracerebral Transplants

The Hoechst dye staining method has been successfully applied to the central nervous system in mammals and its use has been demonstrated in intracerebral transplantation. The technique is rapid, simple and based on intrinsic nuclear properties. It was found to be permanent and valid whatever the animal strains or ages, allowing the distinction of rat cells from those of mouse, studied either separately or in a cross-transplantation model. It permitted the detection of grafted cells in the area of transplantation and the observation of early dispersion around the implantation site. Moreover, it can be combined with immunohistochemistry as demonstrated by a myelin marker in a relevant model. Immunodetection can thus help to directly observe grafted cells, at distance from the locus of transplantation, confirming their presence in the graft-type myelin patches.

Because of its rapid performance, this technique can be used systematically after transplantation to check for the presence of grafted cells in the host.     

Molecular modelling of protein-carbohydrate interactions. Understanding the specificities of two legume lectins towards oligosaccharides

By means of a series of new molecular modelling tools, the conformationalbehaviour of mannose-containing di- and trisaccharides boundto either concanavalin A or Lathyrus ochrus isolectin I (LOLI)has been assessed. Tools for estimating and analysing eitherthe ‘rigid’ or the ‘relaxed’ potentialenergy surfaces, representing the conformational space availablefor carbohydrates once interacting with lectins, are reportedfor the first time. Restrictions of conformational space arepredicted to occur with different magnitudes, depending on thenature of the glycosidic linkages, as well as the size of thecarbohydrates. Results from these molecular modelling studiesare compared to existing structural data. Not only could theobserved conformations and orientations of carbohydrates incrystalline lectin–oligosaccharides complexes be reproduced,but several other likely situations were also predicted to occur.Entropy calculations have been performed for comparison withexperimental thermodynamics data. The results of the simulationcan also help giving an explanation of some observed affinityconstants at the molecular level. concanavalin A Lathyrus ochrus lectin-oligosaccharide molecular modelling     

Does Manganese Protect Cultured Human Skin Fibroblasts Against Oxidative Injury by Uva, Dithranol and Hydrogen Peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H₂O₂ cytotoxicity.     

Multi-year sampling provides insight into the bet-hedging capacity of the soil-stored seed reserve of a threatened Acacia species from Western Australia

This multi-year study examined temperature requirements for dormancy release in physically dormant seeds of the threatened legume Acacia awestoniana (Fabaceae) from Western Australia. Seeds were collected from a single site in three consecutive years and exposed to multiple laboratory-based ‘fire’-related temperature treatments (intensity × duration). Experiments were conducted on seeds freshly collected and after 12 months storage under dry laboratory conditions in order to separate the influence of the maternal environment from post-harvest storage conditions on thresholds for dormancy release. Initial seed viability and non-dormant seed fraction did not differ between seed cohorts but there was a clear effect of storage on seed response: fresh seeds from 2016 demonstrated greater thermal resilience than stored seeds collected in the same year. Equally, there was a strong inter-annual response to treatments from fresh seeds collected in 2016 and 2017 attributed to the influence of the maternal environment during seed development. Seeds collected in 2015 and 2016 and stored for 12 months also demonstrated significant differences in their response to treatments, with 2015 seeds responding more favourably to treatment conditions than those from 2016. Plastic responses to external stimuli provide seeds with a strong bet-hedging capacity and the potential to cope with high levels of environmental heterogeneity, especially a mosaic of fire conditions. Such data provide insight for the management, conservation and restoration of this and similar threatened plant species in fire-prone ecosystems in the face of a rapidly changing climate and expected associated changes in the fire regime.