Prevention and treatment of cardiovascular instability during spinal anaesthesia for caesarean section

Spinal anaesthesia is the method of choice for caesarean section. There is however a significant associated morbidity and mortality in South Africa, particularly in inexperienced hands. This review provides recommendations for safe practice for anaesthetists at all levels of expertise, with particular reference to the management of haemodynamic instability. S Afr Med J 2004; 94: 367-372

A qualitative study exploring therapists' experiences of implementing a complex intervention promoting meaningful activity for residents in care homes

Objectives: To explore the experiences of occupational therapists and physiotherapists and to reveal any factors that can facilitate delivering a complex care home intervention promoting meaningful activity. Design: Qualitative interview study using data from three focus groups conducted longitudinally post intervention implementation. Data were analysed thematically. Setting: Three residential care homes in South London, UK. Subjects: All therapists involved in the implementation of the intervention: three occupational therapists and three physiotherapists. Results: Three interconnected themes emerged from the analysis: (1) developing trusting relationships, (2) empowering staff and (3) remaining flexible. Therapists described how successfully implementing a complex care home intervention was dependant on developing trusting relationships with care staff. This enabled the therapists to empower care staff to take ownership of the intervention and help embed it in care home culture, facilitating long-term change. The therapists described how remaining flexible in their approach helped keep care staff engaged for the duration of implementation. Conclusion: This study has revealed several important factors that can help facilitate therapists delivering complex interventions in care homes

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

A practical guide to photoacoustic tomography in the life sciences

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs

Alcohol consumption and body composition in a population-based sample of elderly Australian men

Background: Alcohol is calorie dense, and impacts&nbsp;activity, appetite and lipid processing. The aim of this&nbsp;study was to therefore investigate the association between&nbsp;alcohol consumption and components of body composition&nbsp;including bone, fat and lean tissue.Methods: Participants were recruited from a randomly&nbsp;selected, population-based sample of 534 men aged&nbsp;65 years and older enrolled in the Geelong Osteoporosis&nbsp;Study. Alcohol intake was ascertained using a food&nbsp;frequency questionnaire and the sample categorised as nondrinkers or alcohol users who consumed B2, 3&ndash;4 or C5&nbsp;standard drinks on a usual drinking day. Bone mineral&nbsp;density (BMD), lean body mass and body fat mass were&nbsp;measured using dual energy X-ray absorptiometry; overall&nbsp;adiposity (%body fat), central adiposity (%truncal fat) and&nbsp;body mass index (BMI) were calculated. Bone quality was&nbsp;determined by quantitative heel ultrasound (QUS).Results: There were 90 current non-drinkers (16.9 %),&nbsp;266 (49.8 %) consumed 1&ndash;2 drinks/day, 104 (19.5 %) 3&ndash;4&nbsp;drinks/day and 74 (13.8 %) C5 drinks/day. Those consuming C5 drinks/day had greater BMI (?4.8 %), fat mass&nbsp;index (?20.1 %), waist circumference (?5.0 %), %body&nbsp;fat (?15.2 %) and proportion of trunk fat (?5.3 %) and&nbsp;lower lean mass (-5.0 %) than non-drinkers after adjustment for demographic and lifestyle factors. Furthermore,&nbsp;they were more likely to be obese than non-drinkers&nbsp;according to criteria based on BMI (OR = 2.83, 95 %CI&nbsp;1.10&ndash;7.29) or waist circumference (OR = 3.36, 95 %CI&nbsp;1.32&ndash;8.54). There was an inverse relationship between&nbsp;alcohol consumption and QUS parameters and BMD at the&nbsp;mid forearm site; no differences were detected for BMD at&nbsp;other skeletal sites.Conclusion:&nbsp;Higher alcohol intake was associated with&nbsp;greater total and central adiposity and reduced bone&nbsp;quality.<br /

Development and Clinical Evaluation of a Rapid Serodiagnostic Test for Toxoplasmosis of Cats Using Recombinant SAG1 Antigen

Rapid serodiagnostic methods for Toxoplasma gondii infection in cats are urgently needed for effective control of transmission routes toward human infections. In this work, 4 recombinant T. gondii antigens (SAG1, SAG2, GRA3, and GRA6) were produced and tested for the development of rapid diagnostic test (RDT). The proteins were expressed in Escherichia coli, affinity-purified, and applied onto the nitrocellulose membrane of the test strip. The recombinant SAG1 (rSAG1) showed the strongest antigenic activity and highest specificity among them. We also performed clinical evaluation of the rSAG1-loaded RDT in 182 cat sera (55 household and 127 stray cats). The kit showed 0.88 of kappa value comparing with a commercialized ELISA kit, which indicated a significant correlation between rSAG1-loaded RDT and the ELISA kit. The overall sensitivity and specificity of the RDT were 100% (23/23) and 99.4% (158/159), respectively. The rSAG1-loaded RDT is rapid, easy to use, and highly accurate. Thus, it would be a suitable diagnostic tool for rapid detection of antibodies in T. gondii-infected cats under field conditions

Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon

Using data collected by the CLEO detector in the Upsilon(4S) region, we report new measurements of the exclusive decays of B mesons into final states of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes with one, two and three pions and an upper limit for the two body decay Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one and two pions and an upper limit for the two body decay Sigma_c p-bar. Measurements of these modes shed light on the mechanisms involved in B decays to baryons.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Prion Shedding from Olfactory Neurons into Nasal Secretions

This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrPSc, was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrPSc co-localized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 103.9 median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrPSc amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants

Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons

Using data recorded by the CLEO II and CLEO II.V detector configurations at CESR, we report new measurements of the masses of the Sigma_c^{++} and Sigma_c^0 charmed baryons, and the first measurements of their intrinsic widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) = 167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid Communications. Reference [13] correcte