The social stigma of sexual immorality is inscripted in constitutions, laws, and statutes in the Caribbean and justified and legitimated through references to Christian doxa. This induces forms of ...structural stigma through policies and practices of governance. I employ country comparisons to demonstrate the critical effect on rates of HIV/AIDS of structural stigma induced by these inscriptions in Caribbean countries. By comparing rates of HIV/AIDS across selected countries, I analyse the differing patterns of structural stigma against the latter's relationship with structural vulnerabilities associated with poverty, underdevelopment, government incapacities, and population flows. I conclude that significant reductions in rates of prevalence can be achieved when social stigma is minimised or meliorated through effective government action or through the influence of external actors, even in the presence of other forms of structural vulnerabilities. The intensity of population flows into a country can also act independently to increase rates of prevalence, even in the face of reductions in structural stigma related to sexual immorality.
Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation and apoptosis. Multiple ...mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies, with the CHCHD2-T61I mutation being the most widely studied. However, at present, only CHCHD2 knockout or CHCHD2/CHCHD10 double knockout mouse models have been investigated. They do not recapitulate the pathology seen in patients with CHCHD2 mutations. We generated the first transgenic mouse model expressing the human PD-linked CHCHD2-T61I mutation driven by the mPrP promoter. We show that CHCHD2-T61I Tg mice exhibit perinuclear mitochondrial aggregates, neuroinflammation, and have impaired long-term synaptic plasticity associated with synaptic dysfunction. Dopaminergic neurodegeneration, a hallmark of PD, is also observed along with α-synuclein pathology. Significant motor dysfunction is seen with no changes in learning and memory at 1 year of age. A minor proportion of the CHCHD2-T61I Tg mice (~10%) show a severe motor phenotype consistent with human Pisa Syndrome, an atypical PD phenotype. Unbiased proteomics analysis reveals surprising increases in many insoluble proteins predominantly originating from mitochondria and perturbing multiple canonical biological pathways as assessed by ingenuity pathway analysis, including neurodegenerative disease-associated proteins such as tau, cofilin, SOD1 and DJ-1. Overall, CHCHD2-T61I Tg mice exhibit pathological and motor changes associated with LBDs, indicating that this model successfully captures phenotypes seen in human LBD patients with CHCHD2 mutations and demonstrates changes in neurodegenerative disease-associated proteins, which delineates relevant pathological pathways for further investigation.
Physical activity monitoring technology (e.g. smartphone apps or wearables) can objectively record physical activity levels, potentially support interventions to increase activity levels, and support ...the self-management of Chronic Obstructive Pulmonary Disease (COPD). Insight into patients' experiences of monitoring physical activity is needed to inform future healthcare practice and policy utilizing this technology to support long-term positive health behavior change. This scoping review aimed to explore the experiences of using technology for monitoring physical activity among people with COPD. The Joanna Briggs Institute scoping review methodological framework was used. Relevant scientific databases (CINAHL Complete, MEDLINE, PsycINFO, SPORTDiscus, Cochrane Library and Scopus) were searched from 1st January 2016 to 16th March 2021. Thematic synthesis was used to analyze the data. Twelve studies exploring the experiences of people with COPD using technology for monitoring physical activity were included in the synthesis. Seven themes were developed and summarize experiences: 1) Monitoring and keeping track of their activity and health, 2) Supporting motivation to be active, 3) Acceptability of the device, 4) Experiencing technical issues with the device, 5) Setting appropriate and achievable goals for their health condition, 6) Integrating the device into their life and daily routine, and 7) Perceived physical and psychological benefits of using the device. Further high-quality research is needed to understand the experiences of people with COPD using technology to monitor physical activity in everyday life and better self-manage their health condition. Supporting people with COPD to monitor their physical activity could enable them to better self-manage their health condition.
Arrestins are multifunctional proteins that regulate G-protein-coupled receptor (GPCR) desensitization, signaling, and internalization. The arrestin family consists of four subtypes: visual ...arrestin1, β-arrestin1, β-arrestin2, and visual arrestin-4. Recent studies have revealed the multifunctional roles of β-arrestins beyond GPCR signaling, including scaffolding and adapter functions, and physically interacting with non-GPCR receptors. Increasing evidence suggests that β-arrestins are involved in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). β-arrestins physically interact with γ-secretase, leading to increased production and accumulation of amyloid-beta in AD. Furthermore, β-arrestin oligomers inhibit the autophagy cargo receptor p62/SQSTM1, resulting in tau accumulation and aggregation in FTD. In PD, β-arrestins are upregulated in postmortem brain tissue and an MPTP model, and the β2AR regulates SNCA gene expression. In this review, we aim to provide an overview of β-arrestin1 and β-arrestin2, and describe their physiological functions and roles in neurodegenerative diseases. The multifaceted roles of β-arrestins and their involvement in neurodegenerative diseases suggest that they may serve as promising therapeutic targets.
Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. ...Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co‐administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors’ Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018.
INTRODUCTIONActivity monitors (apps and wearables) are increasingly used by the general population, including people with Chronic Obstructive Pulmonary Disease (COPD). There is potential for activity ...monitors to support increases in physical activity for people with COPD and healthcare practitioners (HCPs) are likely to be key in supporting their use, but little is currently known about HCPs' views or experiences. This qualitative research aimed to explore HCPs' views and experiences of supporting people with COPD who have used activity monitors.METHODSSeventeen semi-structured telephone or online interviews were conducted with HCPs between September 2020 and May 2021. HCPs included two nurses, an occupational therapist, a physician, and 13 physiotherapists. Participants were recruited via social media advertisements. They all had experience of supporting people with COPD who had used activity monitors. Interviews were analysed using reflexive thematic analysis.FINDINGSFour themes were developed highlighting the challenges and benefits of HCPs supporting patients with using activity monitors and utilising patient-collected activity data; 1) Skills and experience are needed to increase accessibility and engagement, 2) Objectively monitored physical activity can support exercise prescription, 3) Applications of activity monitors vary across different settings, and 4) Support is needed for future use of activity monitors.DISCUSSIONHCPs recognised the potential for activity monitors to impact patients' ability to self-manage their COPD. However, there is a lack of guidance and information to support integration within practice. Future research is needed to co-develop information and guidelines for people with COPD and HCPs.
Key message
QTL
identified for seedling and adult plant crown rot resistance in four partially resistant hexaploid wheat sources. PCR-based markers identified for use in marker-assisted selection.
...Crown rot, caused by
Fusarium pseudograminearum
, is an important disease of wheat in many wheat-growing regions globally. Complete resistance to infection by
F. pseudograminearum
has not been observed in a wheat host, but germplasm with partial resistance to this pathogen has been identified. The partially resistant wheat hexaploid germplasm sources 2-49, Sunco, IRN497 and CPI133817 were investigated in both seedling and adult plant field trials to identify markers associated with the resistance which could be used in marker-assisted selection programs. Thirteen different quantitative trait loci (QTL) conditioning crown rot resistance were identified in the four different sources. Some QTL were only observed in seedling trials whereas others appeared to be adult plant specific. For example while the QTL on chromosomes 1AS, 1BS, and 4BS contributed by 2-49 and on 2BS contributed by Sunco were detected in both seedling and field trials, the QTL on 1DL present in 2-49 and the QTL on 3BL in IRN497 were only detected in seedling trials. Genetic correlations between field trials of the same population were strong, as were correlations between seedling trials of the same population. Low to moderate correlations were observed between seedling and field trials. Flanking markers, most of which are less than 10 cM apart, have now been identified for each of the regions associated with crown rot resistance.
Illustrated with many photographs of the expeditions, as well as of the collections, Men in Search of Man contains several supplements listing additional information pertinent to the history of the ...museum.
In what he terms ‘the dialectics of imperialism’ Harvey points to a ‘crisis’ stemming from ‘overaccumulation’ in the global north that creates a perpetual need for new markets, new investment ...opportunities, and new sources of raw materials. What happens when, as a result, the crisis spreads globally? Scholars have identified this global phase as a ‘new epoch in the evolution of world capitalism’ that is marked by ‘novel articulations of social power’ (Robinson, 2014). It is characterized by a shift from a world economy organized around relations among sovereign nations, to a ‘global economy’ characterized by transnational flows and formations. The ensuing ‘crisis’ is turning out to be an existential one that, as was pointed out by Wallerstein over a decade ago, ‘cannot be resolved within the framework of the system … only by going outside and beyond’ its historical formation. This raises fundamental questions about the constitution of the state and its relationship to national governance, or what Robinson calls ‘nation-state centric paradigms’. Both, as it turns out, may be the product of universalized discourses that, as Chakrabarty and Stoler assert, distort the constellation of social forces and their relationship to modern institutional and identity formations. I would like to deal with these distortions and what the current crisis may reveal about the entanglements of the state, capitalism, national government, and identity formation.
Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, ...apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management.
For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers) was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using chi2 or Fisher's exact test.
APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2), endometrial cancer (CASP8, CDH13, hMLH1 and p73), and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1). The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers) were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Aberrant methylation for some genes (BRCA1, DAPK, hMLH1, MGMT, p14, p16, and PTEN) was also associated with clinico-pathological data.
Thus, differential methylation profiles occur in the three types of gynecologic cancer. Detection of methylation for critical loci is potentially useful as epigenetic markers in tumor classification. More studies using a much larger sample size are needed to define the potential role of DNA methylation as marker for cancer management.
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