3,251 research outputs found

    An audit of antenatal education facilitated by physiotherapists in Western Australian public hospitals

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    This paper reports on the delivery of antenatal education by physiotherapists in Western Australia in 2012, including the location of antenatal education providers, number of mothers attending, qualifications of physiotherapists involved, allocation of physiotherapy hours, the content of the education, and strategies used to enhance learning in the classes. A survey was emailed to the physiotherapists in 31 hospitals with maternity services that were funded by the Department of Health Western Australia. Antenatal education facilitated by a physiotherapist was provided at 25/30 (83.3%) hospitals. Four physiotherapists had postgraduate women’s health qualifications and all the antenatal education classes provided information about pelvic floor muscle exercises. There was a wide variation in pelvic floor muscle exercise prescription. Fewer than 50% of first-time mothers who give birth in the public sector have attended physiotherapy facilitated antenatal education classes

    High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours

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    <p>Abstract</p> <p>Background</p> <p>Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS) is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information.</p> <p>Methods</p> <p>Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe). Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping.</p> <p>Results</p> <p>Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours. Classification accuracy was 90%. Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%. Supratentorial primitive neuro-ectodermal tumours had metabolite profiles in keeping with other primitive neuro-ectodermal tumours whilst ependymomas (n = 2) had metabolite profiles intermediate between pilocytic astrocytomas (n = 10) and primitive neuro-ectodermal tumours.</p> <p>Conclusion</p> <p>HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.</p

    Measurement of low‐density lipoprotein cholesterol levels in primary and secondary prevention patients: Insights from the PALM registry

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    Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low-density lipoprotein cholesterol ( LDL -C) to identify untreated patients with LDL -C ≥190 mg/dL, assess lipid-lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL -C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL -C levels measured in the 2 years before enrollment. Patients without chart-documented LDL -C levels were more often women, nonwhite, uninsured, and non-college graduates (all P\u3c0.01). Patients without prior lipid testing were less likely to receive statin treatment (72.6% versus 76.0%; P=0.0034), a high-intensity statin (21.5% versus 24.3%; P=0.016), nonstatin lipid-lowering therapy (24.8% versus 27.3%; P=0.037), and had higher core laboratory LDL -C levels at enrollment (median 97 versus 92 mg/dL; P\u3c0.0001) than patients with prior LDL -C testing. Of 166 individuals with core laboratory LDL -C levels ≥190 mg/dL, 36.1% had no LDL -C measurement in the prior 2 years, and 57.2% were not on a statin at the time of enrollment. Conclusions In routine clinical practice, LDL -C testing is associated with higher-intensity lipid-lowering treatment and lower achieved LDL -C level

    Introduction of Macromolecules into Bovine Adrenal Medullary Chromaffin Cells and Rat Pheochromocytoma Cells (PC12) by Permeabilization with Streptolysin O: Inhibitory Effect of Tetanus Toxin on Catecholamine Secretion

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    Conditions are described for controlled plasma membrane permeabilization of rat pheochromocytoma cells (PC12) and cultured bovine adrenal chromaffin cells by Streptolysin O (SLO). The transmembrane pores created by SLO invoke rapid efflux of intracellular 86Rb+ and ATP, and also permit passive diffusion of proteins, including immunoglobulins, into the cells. SLO-permeabilized PC12 cells release [3H]dopamine in response to micromolar concentrations of free Ca2+. Permeabilized adrenal chromaffin cells present a similar exocytotic response to Ca2+ in the presence of Mg2+/ ATP. Permeabilized PC12 cells accumulate antibodies against synaptophysin and calmodulin, but neither antibody reduces the Ca2+-dependent secretory response. Reduced tetanus toxin, although ineffective when applied to intact chromaffin cells, inhibits Ca2+-induced exocytosis by both types of permeabilized cells studied. Omission of dithiothreitol, toxin inactivation by boiling, or preincubation with neutralizing antibodies abolishes the inhibitory effect. The data indicate that plasma membrane permeabilization by Streptolysin O is a useful tool to probe and define cellular components that are involved in the final steps of exocytosis

    The effects of exurbanization on the food and habitat of pileated woodpeckers

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    *Background/Question/Methods* &#xd;&#xa;_Dryocopus pileatus_ (pileated woodpeckers) are the largest woodpeckers in the United States. They require large trees for roosting, nesting, and feeding and these trees must be dead or dying for ease of excavation and presence of the woodpeckers&#x27; main prey of ants and grubs. Because of these habitat requirements, pileated woodpeckers are used as an indicator species for mature forests. However, their status in exurban areas, or places of low-density development beyond the suburban fringe, is poorly known. Because exurbanization covers a large and growing portion of the eastern U.S.A., we examined how pileated woodpeckers and their habitat vary across a gradient of exurbanization. We tested the hypothesis that presence of pileated woodpeckers is positively correlated with forest structure and food availability, in exurban and forested areas. We conducted the study in Sewanee, Tennessee, U.S.A., establishing 30 randomly located sample points evenly divided between exurban and forested areas. At each point we assessed pileated woodpecker presence through visual and vocal surveys; forest structure through measures of downed wood, standing trees, and understory density; and food availability through presence of ants and grubs in soil cores and pitfall traps.&#xd;&#xa;&#xd;&#xa;*Results/Conclusions* &#xd;&#xa;We found no difference between the presence of pileated woodpeckers, amount and rot class of dead wood, and ant and grub abundance between exurban and forested areas. Mean tree diameter was larger in exurban areas most likely because many small trees had been removed by human landscaping. These data suggest that some exurban areas may provide habitat for pileated woodpeckers. However, more studies are needed to examine the breeding success and survival rates of pileated woodpeckers in exurban and forested areas. Because the mature forest characteristics that pileated woodpeckers prefer can be found in exurban areas, it is possible that other species requiring these characteristics could also find usable habitat in exurban areas. This could apply most specifically to those secondary cavity-nesting species that use old pileated woodpecker nesting cavities. More studies should be conducted to further explore the effects of exurbanization on other species that are thought of as indicating mature forests

    Biochemical analysis of novel NAA10 variants suggests distinct pathogenic mechanisms involving impaired protein N-terminal acetylation

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    NAA10 is the catalytic subunit of the N-terminal acetyltransferase complex, NatA, which is responsible for N-terminal acetylation of nearly half the human proteome. Since 2011, at least 21 different NAA10 missense variants have been reported as pathogenic in humans. The clinical features associated with this X-linked condition vary, but commonly described features include developmental delay, intellectual disability, cardiac anomalies, brain abnormalities, facial dysmorphism and/or visual impairment. Here, we present eight individuals from five families with five different de novo or inherited NAA10 variants. In order to determine their pathogenicity, we have performed biochemical characterisation of the four novel variants c.16G>C p.(A6P), c.235C>T p.(R79C), c.386A>C p.(Q129P) and c.469G>A p.(E157K). Additionally, we clinically describe one new case with a previously identified pathogenic variant, c.384T>G p.(F128L). Our study provides important insight into how different NAA10 missense variants impact distinct biochemical functions of NAA10 involving the ability of NAA10 to perform N-terminal acetylation. These investigations may partially explain the phenotypic variability in affected individuals and emphasise the complexity of the cellular pathways downstream of NAA10.publishedVersio

    The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

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    The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro
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