Notes

[Primary delayed expansion of the right and left atrial myxoma].
Histamine has been implicated in urinary bladder dysfunction as an inflammatory mediator driving sensory nerve hypersensitivity. However, the direct influence of histamine on smooth muscle has not been thoroughly investigated. We hypothesized that histamine directly contracts urinary bladder smooth muscle (UBSM) independent of effects on nerves. Single cell quantitative RT-PCR determined that only histamine H1 and H2 receptors were expressed on UBSM cells. In isolated tissue bath experiments, histamine (200 µM) caused a highly variable and rapidly desensitizing contraction that was completely abolished by the H1 receptor antagonist fexofenadine (5 µM) and the Gq/11 inhibitor YM254890 (1 µM). Neither the muscarinic receptor antagonist atropine (1 µM), the Na+ channel blocker tetrodotoxin (1 µM), nor the transient receptor potential vanilloid type 1 antagonist capsazepine (10 µM) altered responses to histamine, suggesting that nerve activation was not involved. UBSM desensitization to histamine was not due to rtractility. Histamine contracts the bladder, but this response is highly variable and desensitizes completely in minutes. This desensitization is not due to internalization of the receptor or metabolism of histamine. Because nerve-evoked contractions are also not increased in the presence of histamine, our findings suggest that histamine is not directly acting to change contractility.Calcineurin inhibitors such as cyclosporin A (CsA) have been widely used to improve graft survival following solid-organ transplantation. However, the clinical use of CsA is often limited by its nephrotoxicity. The present study tested the hypothesis that activation of the (pro)renin receptor (PRR) contributes to CsA-induced nephropathy by activating the renin-angiotensin system (RAS). Renal injury in male Sprague-Dawley rats was induced by a low-salt diet combined with CsA as evidenced by elevated plasma creatinine and blood urea nitrogen levels, decreased creatinine clearance and induced renal inflammation, apoptosis and interstitial fibrosis, and elevated urinary N-acetyl-β-d-glucosaminidase activity and urinary kidney injury molecule-1 content. Each index of renal injury was attenuated following 2 wk of treatment with the PRR decoy inhibitor PRO20. Although CsA-treated rats with kidney injury displayed increased renal soluble (s)PRR abundance, plasma sPRR, renin activity, angiotensin II, and heightened urinary total prorenin/renin content, RAS activation was attenuated by PRO20. Exposure of cultured human renal proximal tubular HK-2 cells to CsA induced expression of fibronectin and sPRR production, but the fibrotic response was attenuated by PRO20 and siRNA-mediated PRR knockdown. These findings support the hypothesis that activation of PRR contributes to CsA-induced nephropathy by activating the RAS in rats. Of importance, we provide strong proof of concept that targeting PRR offers a novel therapeutic strategy to limit nephrotoxic effects of immunosuppressant drugs.NEW & NOTEWORTHY The present study reports, for the first time, that activation of the (pro)renin receptor drives the renin-angiotensin system to induce renal injury during cyclosporin A administration. More importantly, our study has identified that antagonism with PRO20 offers a novel intervention in the management of side effects of cyclosporin A.Increased levels of oxidative stress have been found with heart failure. Whether failing hearts express antioxidant and detoxification enzymes have not been addressed systematically. Nrf2 gene encodes a transcription factor that regulates the expression of antioxidant and detoxification genes. Using RNA-Seq data set from explanted hearts of 37 patients with dilated cardiomyopathy (DCM), 13 patients with ischemic cardiomyopathy (ICM), and 14 nonfailure (NF) donors as a control, we addressed whether failing hearts change the expression of Nrf2, its negative regulator Keap1, and antioxidant or detoxification genes. Significant increases in the ratio of Nrf2 to Keap1 were found to associate with DCM or ICM. Antioxidant genes showed decreased expression in both types of heart failure, including NQO1, SOD1, GPX3, GPX4, GSR, PRDX1, and TXNRD1. Detoxification enzymes, GCLM and EPHX1, also showed decreased expression, whereas the CYP1B1 transcript was elevated in both DCM and ICM. The genes encoding metal-binding protein ferritin were decreased, whereas five out of 12 metallothionein genes showed elevated expression. Our finding on Nrf2 gene expression has been validated by meta-analysis of seven independent data sets of microarray or RNA-Seq for differential gene expression in DCM and ICM from NF controls. In conclusion, minor elevation of Nrf2 gene expression is not coupled to increases in antioxidant and detoxification genes, supporting an impairment of Nrf2 signaling in patients with heart failure. Decreases in multiple antioxidant and detoxification genes are consistent with the observed increases of oxidative stress in failing hearts.
There is no model for predicting the outcomes for coronary heart disease (CHD) patients with chronic kidney disease (CKD) after percutaneous coronary intervention (PCI). To develop and validate a model to predict major adverse cardiovascular events (MACEs) in patients with comorbid CKD and CHD undergoing PCI.

We enrolled 1714 consecutive CKD patients who underwent PCI from January 1, 2008 to December 31, 2017. In the development cohort, we used least absolute shrinkage and selection operator regression for data dimension reduction and feature selection. We used multivariable logistic regression analysis to develop the prediction model. Finally, we used an independent cohort to validate the model. The performance of the prediction model was evaluated with respect to discrimination, calibration, and clinical usefulness.

The predictors included a positive family history of CHD, history of revascularization, ST segment changes, anemia, hyponatremia, transradial intervention, the number of diseased vessels, dose of contrast media >200 ml, and coronary collateral circulation. In the validation cohort, the model showed good discrimination (area under the receiver operating characteristic curve, 0.612; 95% confidence interval 0.560, 0.664) and good calibration (Hosmer-Lemeshow test, P  = 
.444). Decision curve analysis demonstrated that the model was clinically useful.

We created a nomogram that predicts MACEs after PCI in CHD patients with CKD and may help improve the screening and treatment outcomes.
We created a nomogram that predicts MACEs after PCI in CHD patients with CKD and may help improve the screening and treatment outcomes.Ageing populations have resulted in more patients living in long-term care or nursing homes, where they face challenges to accessing prompt specialist care exacerbated in many cases by physical or cognitive decline. Electronic consultation has demonstrated an ability to improve access to specialist care for vulnerable groups and offers a potential solution to this gap in care. To support electronic consultation's uptake among long-term care homes, we created the electronic consultation long-term care utilization and savings estimator, an Excel-based tool that estimates the number of off-site appointments that patients in a long-term care home could avoid through electronic consultation, along with the consequent time and cost savings. In this brief report, we discuss the electronic consultation long-term care utilization and savings estimator's creation and function, and provide a case study using long-term care data to demonstrate its potential impact. We anticipate the electronic consultation long-term care utilization and savings estimator will be a highly impactful tool and intend to test it in real-world conditions following the relaxation of COVID-19 restrictions.Introduction Telemedicine and remote patient monitoring are rapidly growing fields. This scoping review provides an update on remote patient monitoring for neuropsychiatric disorders from recent publications and upcoming clinical trials. Methods Publications (PubMed and ICHUSHI; published January 2010 to February 2021) and trials (ClinicalTrials.gov and Japanese registries; active or recruiting by March 2021) that assessed wearable devices for remote management and/or monitoring of patients with neuropsychiatric disorders were searched. The review focuses on disorders with ≥3 publications. Results We identified 44 publications and 51 active or recruiting trials, mostly from 2019 or 2020. Research on digital devices was most common for Parkinson's disease (11 publications and 19 trials), primarily for monitoring motor symptoms and/or preventing falls. Other disorders (3-5 publications each) included epilepsy (electroencephalogram [EEG] and seizure prediction), sleep disorder (sleep outcomes and behavioral therapies), multiple sclerosis (physical activity and symptoms), depression (physical activity, symptoms, and behavioral therapies), and amyotrophic lateral sclerosis (symptoms). Very few studies focused on newly emerging technologies (e.g., in-ear EEG and portable oximeters), and few studies integrated remote symptom monitoring with telemedicine. Discussion Currently, development of digital devices for daily symptom monitoring is focused on Parkinson's disease. For the diseases reviewed, studies mostly focused on physical activity rather than psychiatric or nonmotor symptoms. Although the validity and usefulness of many devices are established, models for implementing remote patient monitoring in telehealth settings have not been established. Conclusions Verification of the clinical effectiveness of digital devices combined with telemedicine is needed to further advance remote patient care for neuropsychiatric disorders.Purpose Sexual and gender minority (SGM) people-including members of lesbian, gay, bisexual, transgender, and queer communities-remain underrepresented in health research due to poor collection of sexual orientation and gender identity (SOGI) data. We sought to understand the contextual factors affecting how SGM research participants interact with SOGI questions to enhance participant experience and increase the accuracy and sensitivity of research findings. Cefodizime purchase Methods We recruited SGM adults for in-person semi-structured focus groups or online cognitive interviews from 2016 to 2018. During focus groups and cognitive interviews, we asked participants to respond to SOGI question sets. We employed template analysis to describe the contextual factors that affected SGM participants' responses to SOGI questions. Results We had a total of 74 participants, including 55 participants organized into nine focus groups and 19 participants in cognitive interviews. Most self-identified as a sexual minority person (88%), and 51% identified as a gender minority person. Two main themes were (1) the need to know the relevance (of why SOGI questions are asked) and (2) the importance of environmental and contextual cues (communicating physical safety and freedom from discrimination that influenced SOGI disclosure). Conclusions Contextualizing the relevance of SOGI data sought could help improve the accuracy and sensitivity of data collection efforts. Environmental cues that communicate acceptance and safety for SGM individuals in research settings may support disclosure. Researchers should consider these contextual factors when designing future studies to improve research experiences for SGM individuals and increase the likelihood of future participation.
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