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Aim To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens-Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results The biological pathways which were significantly enriched in differentially expressed genes in Stevens-Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. selleck compound Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*5801 carriers. Conclusion Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*5801 carriers.E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. link2 In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.Transmembrane proteins (TMEMs), spanning the entire width of lipid bilayers and anchored to them permanently, exist in diverse cell types to implement a series of essential physiological functions. Recently, TMEM48, a member of the TMEM family, has been demonstrated to be closely associated with tumorigenesis. However, little is known about the specific role of TMEM48 in cervical cancer (CC). This study aimed to investigate the biological functions of TMEM48 in CC. The CCK-8 assay was performed to detect CC cell proliferation. link3 The wound healing and transwell assays were conducted to measure cell migration and invasion, respectively. The levels of TMEM48, β-catenin, T cell factor 1(TCF1) and axis formation inhibitor 2 (AXIN2) were examined by the western blot analysis. Xenograft models were established for the tumorigenesis assay in vivo. The results showed that TMEM48 was overexpressed in CC tissues and cell lines. Knockdown of TMEM48 significantly inhibited CC cell proliferation, migration and invasion in vitro and suppressed CC cell growth in vivo. In addition, the investigation on the molecular mechanisms indicated that TMEM48 down-regulation remarkably decreased the protein levels of β-catenin, TCF1 and AXIN2 in CC cells and TMEM48 exerted its promoting effect on CC progression via activation of the Wnt/β-catenin pathway. Taken together, our study suggested TMEM48 as a promising therapeutic target for CC treatment.A critical component of evaluations of the effectiveness of intimate partner violence prevention programmes involves understanding pathways of change among individuals who participate in such programmes, and the intervention or contextual elements that support or hinder these. This paper draws on qualitative evaluations of four intimate partner violence prevention programmes in Ghana, Rwanda, South Africa and Tajikistan conducted as part of the What Works to Prevent Violence against Women and Girls Programme. Using a comparative case study approach, a secondary analysis was applied to thematically analysed data to explore how and why men and women change in response to different types of programmes across diverse contexts. Similar pathways of change were identified including the value of learning and applying relationship skills to support equitable, non-violent relationships; the importance of participatory approaches to challenge harmful gender norms and allow for group rapport; and the integration of economic empowerment activities to reduce drivers of intimate partner violence and conflict, and promote participants' self-confidence and status. These findings provide insights regarding intervention design and implementation factors pertinent to bring about changes in intimate partner violence.The pandemic caused by SARS-CoV-2 that leads to COVID-19 has had an incalculable impact on society, services, and health professionals, including physiotherapists. The field of physiotherapy is currently facing ongoing challenges and pandemic-related repercussions, with Brazilian physiotherapists being especially affected. This article describes the current scenario in Brazil which has exposed the shortage of professionals and resources and reinforces the need for professional recognition, especially of those working in intensive care units. Barriers and challenges faced by Brazilian physiotherapists during the COVID-19 pandemic are described, followed by innovative solutions. Remote physiotherapy prior to the pandemic was merely one of many patient care options, but now has become a necessity, and several international organizations have provided guidelines for physiotherapists to follow, including guidelines on offering digital physiotherapy. Related demands, challenges, and perspectives of physiotherapy practice are likely to emerge amid the current uncertainties of the COVID-19 crisis, as well as during the post-pandemic period. The lessons learned by the Brazilian physiotherapy community may be of assistance to physiotherapists in other countries particularly those with comparable social and demographic characteristics.Background Patients with stable ischemic heart disease represent a heterogeneous population at variable risk for major adverse cardiac events (MACE). Because MACE typically occurs outside the hospital, we studied whether biometric and psychometric remote patient monitoring are associated with MACE risk biomarkers. Methods and Results In 198 patients with stable ischemic heart disease (mean age 65±11 years, 60% women), we evaluated baseline measures, including biometric (FitBit 2) and psychometric (acquired via smartphone-administered patient-reported outcomes) remote monitoring, in the PRE-MACE (Prediction, Risk, and Evaluation of Major Adverse Cardiac Events) study. In multivariable adjusted regression analyses, we examined the association of these measures with biomarkers of MACE risk, including NT-proBNP (N-terminal pro-b-type natriuretic peptide), u-hs-cTnI (ultra-high sensitivity cardiac-specific troponin I), and hs-CRP (high-sensitivity C-reactive) protein. Both biometric and psychometric measures were associated with NT-proBNP. Specifically, step count, heart rate, physical activity, global health score, and physical function score were all inversely related, whereas physical limitation score was directly related (P≤0.05 for all). However, only biometric measures (step count and heart rate) were associated with u-hs-cTnI (inversely related, P less then 0.05), while only the psychometric measures of physical limitation were associated with hs-CRP (directly related, P≤0.05). Conclusions In stable ischemic heart disease patients, remotely monitored measures were associated with MACE risk biomarkers. Both biometric and psychometric measures were related to NT-proBNP. In contrast, biometric measures were uniquely related to u-hs-cTnI, while psychometric indices were uniquely related to hs-CRP. Further investigation could assess the predictive value of these metrics for MACE in ischemic heart disease.The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.Background Life review, a narrative-based intervention, helps individuals organize memories into a meaningful whole, providing a balanced view of the past, present, and future. Examining how the content of memories contributes to life's meaning improves some clinical outcomes for oncology patients. Combining life review with other modalities may enhance therapeutic efficacy. We hypothesized a life review intervention might be enhanced when combined with a kinetic, digital representation (avatar) chosen by the patient. Our goal was to determine the feasibility of an avatar-based intervention for facilitating life review in patients with advanced cancer. Methods We conducted an observational, feasibility trial in a supportive care clinic. Motion capture technology was used to synchronize voice and movements of the patient onto an avatar in a virtual environment. Semistructured life review questions were adapted to the stages of child, teenager, adult, and elder. Outcome measures included adherence, recruitment, comfort of study procedure, patients' perceived benefits, and ability to complete questionnaires, including the Edmonton Symptom Assessment System (ESAS) and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp). Results Seventeen patients were approached, with 11/12 completing the intervention. The total visit time of a single intervention averaged 67 minutes. The post-intervention survey found all patients agreed or strongly agreed (Likert Scale 1-5) they would participate again, would recommend it to others, and found the experience beneficial. After one month, ESAS scores were either unchanged or improved in 80% of patients. Conclusion An avatar-facilitated life review was feasible with a high rate of adherence, completion, and acceptability by patients. The findings support the need for a clinical trial to test the efficacy of this novel intervention. Clinical Trial Number NCT03996642.
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