Propofol Related Infusion Syndrome: A Subtle Adversary

Propofol Related Infusion Syndrome (PRIS) was first described in 1998. It has a strange collection of symptoms, including marked bradycardia, persistent, recalcitrant metabolic acidosis, liver enlargement, rhabdomyolysis, and lipemic blood. We present two recent patients who appeared to have had PRIS. Creatinine kinase seems to be an early detector of PRIS. If PRIS is recognized early, this complex metabolic process seems to be completely reversible

Supporting well-being in retirement through meaningful social roles: Systematic review of intervention studies

Context The marked demographic change toward greater proportions of older people in developed nations poses significant challenges for health and social care. Several studies have demonstrated an association between social roles in later life and positive health and well-being outcomes. After retiring from work, people may lose roles that provide purpose and social contacts. The outcomes of interventions to promote social roles in retirement have not been systematically reviewed. Methods We examined three research questions: (1) What kinds of intervention have been developed to promote social roles in retirement? (2) How much have they improved perceived roles? (3) Have these roles improved health or well-being? We included those studies that evaluated the provision of social roles; used a control or comparison group; targeted healthy retirement-transition adults who were living in the community; provided an abstract written in English; took place in a highly developed nation; and reported social role, health, or well-being outcomes. We searched eight electronic databases and combined the results with hand searches. Findings Through our searches, we identified 9,062 unique publications and eleven evaluative studies of acceptable quality, which reported seven interventions that met our inclusion criteria. These interventions varied in year of inception and scope, but only two were based outside North America. The studies rarely reported the quality or meaning of roles. Only three studies used random allocation, thus limiting inferences of causality from these studies. Interventions providing explicit roles and using supportive group structures were somewhat effective in improving one or more of the following: life satisfaction, social support and activity, physical health and activity, functional health, and cognition. Conclusions Social role interventions may improve health and well-being for people in retirement transition. Future research should improve the quality of intervention and assessment and look at which interventions are most effective and acceptable in facilitating social roles for diverse older populations. © 2013 Milbank Memorial Fund

Are behavioral interventions effective in increasing physical activity at 12 to 36 months in adults aged 55 to 70 years? a systematic review and meta-analysis

Background - Retirement represents a major transitional life stage in middle to older age. Changes in physical activity typically accompany this transition, which has significant consequences for health and well-being. The aim of this systematic review was to evaluate the evidence for the effect of interventions to promote physical activity in adults aged 55 to 70 years, focusing on studies that reported long-term effectiveness. This systematic review adheres to a registered protocol (PROSPERO CRD42011001459). Methods - Randomized controlled trials of interventions to promote physical activity behavior with a mean/median sample age of 55 to 70 years, published between 2000 and 2010, were identified. Only trials reporting the long-term effect (≥ 12 months) on objective or self-reported physical activity behavior were included. Trials reporting physiological proxy measures of physical activity were excluded. Meta-analyses were conducted when trials provided sufficient data and sensitivity analyses were conducted to identify potential confounding effects of trials of poor methodological quality or with attrition rates ≥ 30%. Results - Of 17,859 publications identified, 32 were included which reported on 21 individual trials. The majority of interventions were multimodal and provided physical activity and lifestyle counselling. Interventions to promote physical activity were effective at 12 months (standardized mean difference (SMD) = 1.08, 95% confidence interval (CI) = 0.16 to 1.99, pedometer step-count, approximating to an increase of 2,197 steps per day; SMD = 0.19, 95% CI = 0.10 to 0.28, self-reported physical activity duration outcome), but not at 24 months based on a small subset of trials. There was no evidence for a relationship between intervention effectiveness and mode of delivery or number of intervention contacts; however, interventions which involved individually tailoring with personalized activity goals or provision of information about local opportunities in the environment may be more effective. Conclusions - Interventions in adults aged 55 to 70 years led to long term improvements in physical activity at 12 months; however, maintenance beyond this is unclear. Identified physical activity improvements are likely to have substantial health benefits in reducing the risk of age-related illnesses. These findings have important implications for community-based public health interventions in and around the retirement transition

State-Dependent Firing Determines Intrinsic Dendritic Ca2+ Signaling in Thalamocortical Neurons

Activity-dependent dendritic Ca(2+) signals play a critical role in multiple forms of non-linear cellular output and plasticity. In thalamocortical neurons, despite the well-established spatial separation of sensory and cortical inputs onto proximal and distal dendrites respectively, little is known about the spatio-temporal dynamics of intrinsic dendritic Ca(2+) signalling during the different state-dependent firing patterns that are characteristic of these neurons. Here we demonstrate that T-type Ca(2+) channels are expressed throughout the entire dendritic tree of rat thalamocortical neurons and that they mediate regenerative propagation of low threshold spikes, typical of, but not exclusive to sleep states, resulting in global dendritic Ca(2+) influx. In contrast, actively backpropagating action potentials, typical of wakefulness, result in smaller Ca(2+) influxes that can temporally summate to produce dendritic Ca(2+) accumulations which are linearly related to firing frequency but spatially confined to proximal dendritic regions. Furthermore, dendritic Ca(2+) transients evoked by both action potentials and low threshold spikes are shaped by Ca(2+) uptake by sarco/endoplasmic reticulum Ca(2+) ATP-ases, but do not rely upon Ca(2+)-induced Ca(2+) release. Our data demonstrate that thalamocortical neurons are endowed with intrinsic dendritic Ca(2+) signalling properties that are spatially and temporally modified in a behavioural state-dependent manner, and suggest that backpropagating action potentials faithfully inform proximal sensory but not distal corticothalamic synapses of neuronal output whereas corticothalamic synapses only “detect” Ca(2+) signals associated with low threshold spikes

Antagonistic Mixing in Micelles of Amphiphilic Polyoxometalates and Hexaethylene Glycol Monododecyl Ether

International audienceHypothesis: Polyoxometalates (POMs) are metal oxygen clusters with a range of interesting magnetic and catalytic properties. POMs with attached hydrocarbon chains show amphiphilic behaviour so we hypothesised that mixtures of a nonionic surfactant and anionic surfactants with a polyoxometalate cluster as headgroup would form mixed micelles, giving control of the POM density in the micelle, and which would differ in size and shape from micelles formed by the individual surfactants. Due to the high charge and large size of the POM, we suggested that these would be nonideal mixtures due to the complex interactions between the two types of surfactants. The nonideality and the micellar composition may be quantified using regular solution theory. With supplementary information provided by small-angle neutron scattering (SANS), an understanding of this unusual binary surfactant system can be established.Experiments: A systematic study was performed on mixed surfactant systems containing polyoxometalate-headed amphiphiles (K10[P2W17O61OSi2(CnH(2n+1))2], abbreviated as P2W17-2Cn, where n = 12, 14 or 16) and hexaethylene glycol monododecyl ether (C12EO6). Critical micelle concentrations (CMCs) of these mixtures were measured and used to calculate the interaction parameters based on regular solution theory, enabling prediction of micellar composition. Predictions were compared to micelle structures obtained from SANS. A phase diagram was also established.Findings: The CMCs of these mixtures suggest unusual unfavourable interactions between the two species despite formation of mixed micelles. Micellar compositions obtained from SANS concurred with those calculated using the averaged interaction parameters for P2W17-2Cn/C12EO6 (n = 12 and 14). We attribute the unfavourable interactions to a combination of different phenomena: counterion-mediated interactions between P2W17 units and the unfolding of the ethylene oxide headgroups of the nonionic surfactant, yet micelles still form in these systems due to the hydrophobic interactions between surfactant tails

A 3D ex vivo mandible slice system for longitudinal culturing of transplanted dental pulp progenitor cells

Harnessing mesenchymal stem cells for tissue repair underpins regenerative medicine. However, how the 3D tissue matrix maintains such cells in a quiescent state whilst at the same time primed to respond to tissue damage remains relatively unknown. Developing more physiologically relevant 3D models would allow us to better understand the matrix drivers and influence on cell-lineage differentiation in situ. In this study, we have developed an ex vivo organotypic rat mandible slice model; a technically defined platform for the culture and characterization of dental pulp progenitor cells expressing GFP driven by the β-actin promoter (cGFP DPPCs). Using confocal microscopy we have characterized how the native environment influences the progenitor cells transplanted into the dental pulp. Injected cGFP-DPPCs were highly viable and furthermore differentially proliferated in unique regions of the mandible slice; in the dentine region, cGFP-DPPCs showed a columnar morphology indicative of expansion and lineage differentiation. Hence, we demonstrated the systematic capacity for establishing a dental pulp cell-micro-community, phenotypically modified in the tooth (the “biology”); and at the same time addressed technical challenges enabling the mandible slice to be accessible on platforms for high-content imaging (the biology in a “multiplex” format)

Post transition metal substituted Keggin-type POMs as thin film chemiresistive sensors for H2O and CO2 detection

Chemiresitive sensing allows the affordable and facile detection of small molecules such as H2O and CO2. Herein, we report a novel class of Earth-abundant post transition metal substituted Keggin polyoxometalates (POMs) for chemiresistive sensing applications, with conductivities up to 0.01 S cm−1 under 100% CO2 and 65% Relative Humidity (RH)

Systematic whole-genome sequencing reveals an unexpected diversity among actinomycetoma pathogens and provides insights into their antibacterial susceptibilities

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the β-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment

Mirubactin C rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a protein machine called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg(2+) concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening > 2,000 extracts from a diverse collection of actinobacteria, we identified a compound, mirubactin C, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed using synthetic mirubactin C. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin C rescuing activity is not due simply to iron sequestration. The results support an emerging view that the functions of bacterial siderophores extend well beyond simply iron binding and uptake

Rescue of a chimeric rinderpest virus with the nucleocapsid protein derived from peste-des-petits-ruminants virus: use as a marker vaccine

The nucleocapsid (N) protein of all morbilliviruses has a highly conserved central region that is thought to interact with and encapsidate the viral RNA. The C-terminal third of the N protein is highly variable among morbilliviruses and is thought to be located on the outer surface and to be available to interact with other viral proteins such as the phosphoprotein, the polymerase protein and the matrix protein. Using reverse genetics, a chimeric rinderpest virus (RPV)/peste-des-petits-ruminants virus (PPRV) was rescued in which the RPV N gene open reading frame had been replaced with that of PPRV (RPV–PPRN). The chimeric virus maintained efficient replication in cell culture. Cattle vaccinated with this chimeric vaccine showed no adverse reaction and were protected from subsequent challenge with wild-type RPV, indicating it to be a safe and efficacious vaccine. The carboxyl-terminal variable region of the rinderpest N protein was cloned and expressed in Escherichia coli. The expressed protein was used to develop an indirect ELISA that could clearly differentiate between RPV- and PPRV-infected animals. The possibility of using this virus as a marker vaccine in association with a new diagnostic ELISA in the rinderpest eradication programme is discussed