Synthetic studies of roquefortine C: synthesis of isoroquefortine C and a heterocycle

The syntheses of isoroquefortine C and a related heterocycle were achieved by implementation of both intra- and intermolecular vinyl amidation reactions. These accomplishments represent a significant advance in the use of these strategies in the generation of complex molecules.     

Encouraging patients to self‐care – the preliminary development and validation of the VeLUSET©, a self‐efficacy tool for venous leg ulcer patients,aged 60 years and over

Venous leg ulceration has a high recurrence rate. Patients with healed or frequently recurring venous ulceration are required to perform self‐care behaviours to prevent recurrence or promote healing, but evidence suggests that many find these difficult to perform. Bandura's self‐efficacy theory is a widely used and robust behaviour change model and underpins many interventions designed to promote self‐care in a variety of chronic conditions. By identifying areas where patients may experience difficulty in performing self‐care, interventions can be developed to strengthen their self‐efficacy beliefs in performing these activities successfully. There are currently a variety of self‐efficacy scales available to measure self‐efficacy in a variety of conditions; but not a disease‐specific scale for use with venous ulcer patients. The aim of this study, therefore, was to develop and validate a disease‐specific, patient‐focused self‐efficacy scale for patients with healed venous leg ulceration. This scale will need further validation studies; however, it is ready for use in clinical practice and will enable practitioners to identify those patients who may need additional support in performing self‐care activities to prevent recurrence.     

Soil Dust Aerosols and Wind as Predictors of Seasonal Meningitis Incidence in Niger

Background: Epidemics of meningococcal meningitis are concentrated in sub-Saharan Africa during the dry season, a period when the region is affected by the Harmattan, a dry and dusty northeasterly trade wind blowing from the Sahara into the Gulf of Guinea.Objectives: We examined the potential of climate-based statistical forecasting models to predict seasonal incidence of meningitis in Niger at both the national and district levels.Data and methods: We used time series of meningitis incidence from 1986 through 2006 for 38 districts in Niger. We tested models based on data that would be readily available in an operational framework, such as climate and dust, population, and the incidence of early cases before the onset of the meningitis season in January–May. Incidence was used as a proxy for immunological state, susceptibility, and carriage in the population. We compared a range of negative binomial generalized linear models fitted to the meningitis data.Results: At the national level, a model using early incidence in December and averaged November–December zonal wind provided the best fit (pseudo-R² = 0.57), with zonal wind having the greatest impact. A model with surface dust concentration as a predictive variable performed indistinguishably well. At the district level, the best spatiotemporal model included zonal wind, dust concentration, early incidence in December, and population density (pseudo-R² = 0.41).Conclusions: We showed that wind and dust information and incidence in the early dry season predict part of the year-to-year variability of the seasonal incidence of meningitis at both national and district levels in Niger. Models of this form could provide an early-season alert that wind, dust, and other conditions are potentially conducive to an epidemic.Citation: Pérez García-Pando C, Stanton MC, Diggle PJ, Trzaska S, Miller RL, Perlwitz JP, Baldasano JM, Cuevas E, Ceccato P, Yaka P, Thomson MC. 2014. Soil dust aerosols and wind as predictors of seasonal meningitis incidence in Niger. Environ Health Perspect 122:679–686; http://dx.doi.org/10.1289/ehp.1306640     

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action

Purpose

Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life.

Methods

Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model.

Results

In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model.

Conclusions

Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.     

Crossed responses found in human trapezius muscles are not H‐reflexes

Introduction: We sought to confirm the presence of crossed short‐latency reflexes in trapezius. Methods: Mmax and Hmax were measured in the ipsilateral trapezius in 10 subjects by percutaneous electrical stimulation of the accessory nerve and the cervical nerves of C3/4 respectively. Repeated stimulation of the C3/4 cervical nerves was performed during 3 different tasks (relaxation, contraction of ipsilateral side, contraction of contralateral side). Results: Ipsilaterally, responses increased significantly with an increase in the prestimulus electromyogram (EMG) and decreased significantly with a decrease in prestimulus EMG. Contralateral potentials increased significantly with contraction of the trapezius ipsilateral to the stimulus compared with contraction of the muscle in which they were recorded and decreased significantly with increasing distance from the ipsilateral side. Conclusions: We found ipsilateral and contralateral responses consistent with previous findings. However, we conclude that the contralateral response in trapezius is not a crossed reflex. Muscle Nerve 49 :362–369, 2014     

Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation

Parent‐of‐origin–dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1–6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25‐hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = –0.34 and –0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle‐bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.     

Regulatory T-cells in helminth infection: induction,function and therapeutic potential

Helminth parasites infect an alarmingly large proportion of the world's population, primarily within tropical regions, and their ability to down-modulate host immunity is key to their persistence. Helminths have developed multiple mechanisms that induce a state of hyporesponsiveness or immune suppression within the host; of particular interest are mechanisms that drive the induction of regulatory T-cells (Tregs). Helminths actively induce Tregs either directly by secreting factors, such as the TGF-β mimic Hp-TGM, or indirectly by interacting with bystander cell types such as dendritic cells and macrophages that then induce Tregs. Expansion of Tregs not only enhances parasite survival but, in cases such as filarial infection, Tregs also play a role in preventing parasite-associated pathologies. Furthermore, Tregs generated during helminth infection have been associated with suppression of bystander immunopathologies in a range of inflammatory conditions such as allergy and autoimmune disease. In this review, we discuss evidence from natural and experimental infections that point to the pathways and molecules involved in helminth Treg induction, and postulate how parasite-derived molecules and/or Tregs might be applied as anti-inflammatory therapies in the future.