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A systematic review of barriers and enablers to South Asian women’s attendance for asymptomatic screening of breast and cervical cancers in emigrant countries
Get PDFObjectives The aim of this review was to identify the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance in South Asian populations, in order to improve uptake and propose priorities for further research. Design A systematic review of the literature for inductive, comparative, prospective and intervention studies. We searched the following databases: MEDLINE/In-Process, Web of Science, EMBASE, SCOPUS, CENTRAL, CDSR, CINAHL, PsycINFO and PsycARTICLES from database inception to 23 January 2018. The review included studies on the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance and cervical smear testing (Papanicolaou test) in South Asian populations and those published in the English language. The framework analysis method was used and themes were drawn out following the thematic analysis method. Settings Asymptomatic breast or cervical screening. Participants South Asian women, including Bangladeshi, Indian, Pakistani, Sri Lankan, Bhutanese, Maldivian and Nepali populations. Results 51 included studies were published between 1991 and 2018. Sample sizes ranged from 25 to 38 733 and participants had a mean age of 18 to 83 years. Our review showed that South Asian women generally had lower screening rates than host country women. South Asian women had poorer knowledge of cancer and cancer prevention and experienced more barriers to screening. Cultural practices and assumptions influenced understandings of cancer and prevention, emphasising the importance of host country cultures and healthcare systems. Conclusions High-quality research on screening attendance is required using prospective designs, where objectively validated attendance is predicted from cultural understandings, beliefs, norms and practices, thus informing policy on targeting relevant public health messages to the South Asian communities about screening for cancer
Investigation into the role of an extracellular loop in mediating proton-evoked inhibition of voltage-gated sodium channels
Get PDFProton-evoked activation of sensory neurons is counteracted by inhibition of voltage-gated Na+ channels, and the low acid-sensitivity of sensory neuron of the African naked mole-rat (ANMr) was reported to be due to a strong proton-evoked block of ANMrNav1.7. Here we aimed to reevaluate the role of the suggested negatively-charged motif in the ANMrNav1.7 domain IV P-loop for inhibition by protons. Patch clamp recordings were performed on the recombinant α-subunits Nav1.2–1.8. The insertion of the negatively charged motif (EKE) of ANMrNav1.7 into human Nav1.7 results in an increased proton-evoked tonic inhibition, but also in a reduced channel function. While the voltage-dependency of fast inactivation is changed in hNav1.7-EKE, pH 6.4 fails to induce a significant shift in both constructs. Proton-evoked inhibition of other channel α-subunits reveals a discrete differential inhibition among α-subunits with hNav1.7 displaying the lowest proton-sensitivity. The mutant hNav1.7-EKE displays a similar proton-sensitivity as Nav1.2, Nav1.3, Nav1.6 and Nav1.8. Overall, a correlation between proton-evoked inhibition and motif charge was not evident. Accordingly, a homology model of hNav1.7 shows that the EKE motif residues do not contribute to the pore lumen. Our data confirms that a negative charge of a postulated proton-motif encodes for a high proton-sensitivity when inserted into hNav1.7. However, a negatively charged motif is not a reliable predictor for a high proton-sensitivity in other α-subunits. Given the distance of the proton-motif from the pore mouth it seems unlikely that a blocking mechanism involving direct obstruction of the pore underlies the observed proton-evoked channel inhibition
Bisphenol A Binds to the Local Anesthetic Receptor Site to Block the Human Cardiac Sodium Channel
Get PDFBisphenol A (BPA) has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-gated sodium channel subtype expressed in the human heart. Electrophysiology studies of heterologously-expressed hNav1.5 determined that BPA blocks the channel with a Kd of 25.4±1.3 µM. By comparing the effects of BPA and the local anesthetic mexiletine on wild type hNav1.5 and the F1760A mutant, we demonstrate that both compounds share an overlapping binding site. With a key binding determinant thus identified, an homology model of hNav1.5 was generated based on the recently-reported crystal structure of the bacterial voltage-gated sodium channel NavAb. Docking predictions position both ligands in a cavity delimited by F1760 and contiguous with the DIII–IV pore fenestration. Steered molecular dynamics simulations used to assess routes of ligand ingress indicate that the DIII–IV pore fenestration is a viable access pathway. Therefore BPA block of the human heart sodium channel involves the local anesthetic receptor and both BPA and mexiletine may enter the closed-state pore via membrane-located side fenestrations
Personalised care in patients with chronic pain disorders: educational implications from a population-based study
Get PDFBackground: Personalised care offers psychological benefits to patients with chronic pain disorders. However, it is unclear which patient groups are prioritised, and which ones may require additional educational support in dealing with the psychological impact of chronic pain.
Aim: To assess the relationship between having a chronic pain disorder and the likelihood of being offered a personalised care plan, and also identify underlying psychological vulnerabilities.
Method: Bootstrapping was performed on data from 3717 respondents to the 2014 Health Survey for England. Participants were predominantly female (55.4%) and had a chronic pain disorder: (a) mental illness (anxiety, depression), (b) arthritis, rheumatism, fibrositis, (c) back problems, slipped disc, neck, and (d) other unspecified rheumatic problems (bones, joints, muscles).
Results: Personalised care plans were more likely to be offered to patients with mental health disorders, and experiencing specific psychological issues around feelings of usefulness (Effect = 0.026, 95% CI = 0.001–0.051), decisiveness (Effect = 0.030, 95% CI = 0.008–0.057), and optimism about the future (Effect = −0.028, 95% CI = −0.046 to −0.012). By contrast, patients with arthritis, rheumatism, fibrositis, and other unspecified rheumatic problems (bones, joints, muscles), were less likely to be offered personalised care.
Conclusion: Patients with a rheumatic condition, or other problems of bones, joints, and muscles, might require additional educational support in dealing with the emotional and psychological impact of living with a chronic pain disorder. This should include referral to structured patient education programmes that help improve self-management skills for chronic pain disorders
Recovery Capital. A framework for the contemporary Therapeutic Community?
Get PDFPURPOSE: This paper will critically assess the extent to which recovery capital can provide a theoretical and practical way in which to explore, explain and communicate TC processes and practices . METHOD: A 31-month ethnographic study of one situated residential TC in England. FINDINGS: The findings are usefully thought out as parallels, process and progress. Parallels can be drawn between the recovery capital literature and longstanding TC principles and prescriptions. The term process is significant as it illustrates how concepts proposed by the recovery capital literature can be employed, alongside traditional TC ideals, to create a practice-focused framework that is able to open up day-to-day processes and communicate (within and beyond the TC movement) how and why TCs provide an environment that is conducive to recovery. The ethos and application of the term progress illustrates the fundamental premise of this paper. Recovery capital provides a more contemporary way in which to understand and communicate the work that takes place in a TC. IMPLICATIONS: Synthesising the concepts proposed by both the TC and recovery capital literature provides a contemporary, practice-focused framework for the TC. Thus, re-enforcing the modalities place within an increasingly competitive field
The importance of muscle architecture in biomechanical reconstructions of extinct animals: a case study using Tyrannosaurus rex
Get PDFFunctional reconstructions of extinct animals represent a crucial step towards understanding palaeocological interactions, selective pressures and macroevolutionary patterns in the fossil record. In recent years, computational approaches have revolutionised the field of ‘evolutionary biomechanics’ and have, in general, resulted in convergence of quantitative estimates of performance on increasingly narrow ranges for well studied taxa. Studies of body mass and locomotor performance of Tyrannosaurus rex – arguably the most intensively studied extinct animal – typify this pattern, with numerous independent studies predicting similar body masses and maximum locomotor speeds for this animal. In stark contrast to this trend, recent estimates of maximum bite force in T. rex vary considerably (> 50%) despite use of similar quantitative methodologies. Herein we demonstrate that the mechanistic causes of these disparate predictions are indicative of important and underappreciated limiting factors in biomechanical reconstructions of extinct organisms. Detailed comparison of previous models of T. rex bite force reveals that estimations of muscle fibre lengths and architecture are the principal source of disagreement between studies, and therefore that these parameters represents the greatest source of uncertainty in these reconstructions, and potentially therefore extinct animals generally. To address the issue of fibre length and architecture estimation in extinct animals we present data tabulated from the literature of muscle architecture from over 1100 muscles measured in extant terrestrial animals. Application of this dataset in a reanalysis of T. rex bite force emphasises the need for more data on jaw musculature from living carnivorous animals, alongside increased sophistication of modelling approaches. In the latter respect we predict that implementing limits on skeletal loading into musculoskeletal models will narrow predictions for T. rex bite force by excluding higher‐end estimates
Deep Convolutional Neural Networks for Human Action Recognition Using Depth Maps and Postures
Get PDFIn this paper, we present a method (Action-Fusion) for human action recognition from depth maps and posture data using convolutional neural networks (CNNs). Two input descriptors are used for action representation. The first input is a depth motion image that accumulates consecutive depth maps of a human action, whilst the second input is a proposed moving joints descriptor which represents the motion of body joints over time. In order to maximize feature extraction for accurate action classification, three CNN channels are trained with different inputs. The first channel is trained with depth motion images (DMIs), the second channel is trained with both DMIs and moving joint descriptors together, and the third channel is trained with moving joint descriptors only. The action predictions generated from the three CNN channels are fused together for the final action classification. We propose several fusion score operations to maximize the score of the right action. The experiments show that the results of fusing the output of three channels are better than using one channel or fusing two channels only. Our proposed method was evaluated on three public datasets: 1) Microsoft action 3-D dataset (MSRAction3D); 2) University of Texas at Dallas-multimodal human action dataset; and 3) multimodal action dataset (MAD) dataset. The testing results indicate that the proposed approach outperforms most of existing state-of-the-art methods, such as histogram of oriented 4-D normals and Actionlet on MSRAction3D. Although MAD dataset contains a high number of actions (35 actions) compared to existing action RGB-D datasets, this paper surpasses a state-of-the-art method on the dataset by 6.84%
The Role of DNA Methylation in the Regulation of Skeletal Muscle Atrophy, Hypertrophy and Epigenetic ‘Memory’
Get PDFSkeletal muscle mass is vitally important for the maintenance of health and quality of life into old age, with a plethora of disorders and diseases linked to the loss of this tissue. As a consequence, molecular biologists have extensively investigated both atrophying and hypertrophying skeletal muscle, in order to understand the molecular pathways that are induced to evoke both loss and growth of skeletal muscle. Despite huge progressions in the field, a full understanding of the molecular mechanisms that orchestrate growth and loss in skeletal muscle, remain elusive. In this regard, epigenetics, referring to alterations in gene expression via structural modifications of DNA without fundamental alterations of the DNA code, have recently become a promising area of research, specifically for its role in modulating genetic expression. However, the field of skeletal muscle epigenetics is in its infancy, and as such, there is currently a distinct paucity of research investigating this biological phenomenon. Herein, a genomic approach was utilised to examine the role DNA methylation plays in modulating the response, at both a genetic and phenotypic level, of mammalian skeletal muscle. The methodological and analytical approaches utilised in this thesis identify a number of important, novel and impactful findings. Firstly, it is identified that DNA methylation displays a distinct inverse relationship with gene expression during both muscular atrophy and hypertrophy, these findings are furthered by work identifying that DNA methylation alterations may precede functional changes in gene expression during skeletal muscle hypertrophy. This thesis also elucidated that skeletal muscle possesses an epigenetic memory that creates an enhanced adaptive response to resistance load induced hypertrophy, when the same stimulus was previously encountered. Finally, in human subjects, a number of novel and previously unstudied gene transcripts were identified that display significantly positive correlations with changes in skeletal muscle mass, as evoked by resistance training. The data in this thesis demonstrates an important role for DNA methylation in regulating skeletal muscle mass during periods of both muscle atrophy and hypertrophy, respectively. The work presented here may allow for further work to be conducted, expanding our understanding of epigenetics in skeletal muscle and best facilitating the development of therapeutics that may alleviate the detrimental effects observed during periods of skeletal muscle atrophy
A critical re-evaluation of the Thorne-Zytkow object candidate HV 2112
Get PDFIt has been argued in the literature that the star HV 2112 in the Small Magellanic Cloud (SMC) is the first known example of a Thorne–Żytkow object (TŻO), a red supergiant with a degenerate neutron core. This claim is based on the star having a high luminosity (log (L/L⊙) ≳ 5), an extremely cool effective temperature, and a surface enriched in in lithium, calcium, and various irp-process elements. In this paper we re-examine this evidence, and present new measurements of the stellar properties. By compiling archival photometry from blue to mid-infrared for HV 2112 and integrating under its spectral energy distribution, we find a bolometric luminosity in the range of log (L/L⊙) = 4.70–4.91, lower than that found in previous work and comparable to bright asymptotic giant branch (AGB) stars. We compare a VLT+XSHOOTER spectrum of HV 2112 to other late-type, luminous SMC stars, finding no evidence for enhancements in Rb, Ca, or K, though there does seem to be an enrichment in Li. We therefore conclude that a much more likely explanation for HV 2112 is that it is an intermediate mass (∼5 M⊙) AGB star. However, from our sample of comparison stars we identify a new TŻO candidate, HV 11417, which seems to be enriched in Rb but for which we cannot determine a Li abundance
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