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American Journal of Physiology. Cell... Apr 2024Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the... (Review)
Review
Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the mainstay of heart failure (HF) therapy. In the 1950s and 1960s, we learned that the CTS receptor was part of the sodium pump (NKA) and that the Na/Ca exchanger was critical for the acute cardiotonic effect of digoxin- and ouabain-related CTS. This "settled" view was upended by seven revolutionary observations. First, subnanomolar ouabain sometimes stimulates NKA while higher concentrations are invariably inhibitory. Second, endogenous ouabain (EO) was discovered in the human circulation. Third, in the DIG clinical trial, digoxin only marginally improved outcomes in patients with HF. Fourth, cloning of NKA in 1985 revealed multiple NKA α and β subunit isoforms that, in the rodent, differ in their sensitivities to CTS. Fifth, the NKA is a cation pump and a hormone receptor/signal transducer. EO binding to NKA activates, in a ligand- and cell-specific manner, several protein kinase and Ca-dependent signaling cascades that have widespread physiological effects and can contribute to hypertension and HF pathogenesis. Sixth, all CTS are not equivalent, e.g., ouabain induces hypertension in rodents while digoxin is antihypertensinogenic ("biased signaling"). Seventh, most common rodent hypertension models require a highly ouabain-sensitive α2 NKA and the elevated blood pressure is alleviated by EO immunoneutralization. These numerous phenomena are enabled by NKA's intricate structure. We have just begun to understand the endocrine role of the endogenous ligands and the broad impact of the ouabain-binding site on physiology and pathophysiology.
Topics: Humans; Rats; Animals; Ouabain; Sodium-Potassium-Exchanging ATPase; Ligands; Digoxin; Cardiotonic Agents; Hypertension; Heart Failure; Enzyme Inhibitors; Calcium Signaling; Binding Sites
PubMed: 38223926
DOI: 10.1152/ajpcell.00273.2023 -
AMIA ... Annual Symposium Proceedings.... 2023In 2021, the Association of American Medical Colleges published Telehealth Competencies Across the Learning Continuum, a roadmap for designing telemedicine curricula and...
In 2021, the Association of American Medical Colleges published Telehealth Competencies Across the Learning Continuum, a roadmap for designing telemedicine curricula and evaluating learners. While this document advances educators' shared understanding of telemedicine's core content and performance expectations, it does not include turn-key-ready evaluation instruments. At the University of Oklahoma School of Community Medicine, we developed a year-long telemedicine curriculum for third-year medical and second-year physician assistant students. We used the AAMC framework to create program objectives and instructional simulations. We designed and piloted an assessment rubric for eight AAMC competencies to accompany the simulations. In this monograph, we describe the rubric development, scores for students participating in simulations, and results comparing inter-rater reliability between faculty and standardized patient evaluators. Our preliminary work suggests that our rubric provides a practical method for evaluating learners by faculty during telemedicine simulations. We also identified opportunities for additional reliability and validity testing.
Topics: Humans; Reproducibility of Results; Education, Medical, Undergraduate; Telemedicine; Students; Curriculum; Students, Medical
PubMed: 38222442
DOI: No ID Found -
Environmental Health Perspectives Jan 2024Chemicals that induce mammary tumors in rodents or activate estrogen or progesterone signaling are likely to increase breast cancer (BC) risk. Identifying chemicals with...
BACKGROUND
Chemicals that induce mammary tumors in rodents or activate estrogen or progesterone signaling are likely to increase breast cancer (BC) risk. Identifying chemicals with these activities can prompt steps to protect human health.
OBJECTIVES
We compiled data on rodent tumors, endocrine activity, and genotoxicity to assess the key characteristics (KCs) of rodent mammary carcinogens (MCs), and to identify other chemicals that exhibit these effects and may therefore increase BC risk.
METHODS
Using authoritative databases, including International Agency for Research on Cancer (IARC) Monographs and the US Environmental Protection's (EPA) ToxCast, we selected chemicals that induce mammary tumors in rodents, stimulate estradiol or progesterone synthesis, or activate the estrogen receptor (ER) . We classified these chemicals by their genotoxicity and strength of endocrine activity and calculated the overrepresentation (enrichment) of these KCs among MCs. Finally, we evaluated whether these KCs predict whether a chemical is likely to induce mammary tumors.
RESULTS
We identified 279 MCs and an additional 642 chemicals that stimulate estrogen or progesterone signaling. MCs were significantly enriched for steroidogenicity, ER agonism, and genotoxicity, supporting the use of these KCs to predict whether a chemical is likely to induce rodent mammary tumors and, by inference, increase BC risk. More MCs were steroidogens than ER agonists, and many increased both estradiol and progesterone. Enrichment among MCs was greater for strong endocrine activity vs. weak or inactive, with a significant trend.
DISCUSSION
We identified hundreds of compounds that have biological activities that could increase BC risk and demonstrated that these activities are enriched among MCs. We argue that many of these should not be considered low hazard without investigating their ability to affect the breast, and chemicals with the strongest evidence can be targeted for exposure reduction. We describe ways to strengthen hazard identification, including improved assessments for mammary effects, developing assays for more KCs, and more comprehensive chemical testing. https://doi.org/10.1289/EHP13233.
Topics: Humans; Carcinogens; Cell Transformation, Neoplastic; Estradiol; Estrogens; Progesterone; Animals; Rodentia; Breast Neoplasms; Endocrine Disruptors; DNA Damage; Mammary Neoplasms, Animal
PubMed: 38197648
DOI: 10.1289/EHP13233 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
GeoHealth Dec 2023The protection and management of water resources continues to be challenged by multiple and ongoing factors such as shifts in demographic, social, economic, and public... (Review)
Review
Water, Water Everywhere, but Every Drop Unique: Challenges in the Science to Understand the Role of Contaminants of Emerging Concern in the Management of Drinking Water Supplies.
The protection and management of water resources continues to be challenged by multiple and ongoing factors such as shifts in demographic, social, economic, and public health requirements. Physical limitations placed on access to potable supplies include natural and human-caused factors such as aquifer depletion, aging infrastructure, saltwater intrusion, floods, and drought. These factors, although varying in magnitude, spatial extent, and timing, can exacerbate the potential for contaminants of concern (CECs) to be present in sources of drinking water, infrastructure, premise plumbing and associated tap water. This monograph examines how current and emerging scientific efforts and technologies increase our understanding of the range of CECs and drinking water issues facing current and future populations. It is not intended to be read in one sitting, but is instead a starting point for scientists wanting to learn more about the issues surrounding CECs. This text discusses the topical evolution CECs over time (Section 1), improvements in measuring chemical and microbial CECs, through both analysis of concentration and toxicity (Section 2) and modeling CEC exposure and fate (Section 3), forms of treatment effective at removing chemical and microbial CECs (Section 4), and potential for human health impacts from exposure to CECs (Section 5). The paper concludes with how changes to water quantity, both scarcity and surpluses, could affect water quality (Section 6). Taken together, these sections document the past 25 years of CEC research and the regulatory response to these contaminants, the current work to identify and monitor CECs and mitigate exposure, and the challenges facing the future.
PubMed: 38155731
DOI: 10.1029/2022GH000716 -
Journal of Thoracic Disease Nov 2023Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted... (Review)
Review
BACKGROUND AND OBJECTIVE
Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracic surgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleural infection as indications remain controversial.
METHODS
Systematic review of relevant articles from the PubMed database.
KEY CONTENT AND FINDINGS
Nine non-randomized retrospective studies published between 1996 and 2020 with a total of 2,121 patients were included. Results varied between studies, but overall shorter operative and recovery times and greater patient satisfaction were demonstrated using VATS compared with thoracotomy.
CONCLUSIONS
Although VATS and thoracotomy are viable treatment options for stage II and III pleural infection, VATS has potential advantages in terms of decreased operation time, fewer days with tube drainage, shorter postoperative hospital stay, reduced postoperative pain, increased patient satisfaction with the procedure, and wound appearance. VATS has limitations in the treatment of patients with stage III pleural infection, where delayed surgical referral has been shown to increase the risk of intraoperative conversion to thoracotomy. The data to date implies that debridement by VATS should be proposed as soon as possible in stage II pleural infection and considered in cases of stage III pleural infection.
PubMed: 38090316
DOI: 10.21037/jtd-23-928 -
Plants (Basel, Switzerland) Dec 2023Climate change is one of the most prominent factors influencing the spatial distribution of plants in China, including gymnosperms. Climatic factors influence gymnosperm...
Distribution Patterns of Gymnosperm Species along Elevations on the Qinghai-Tibet Plateau: Effects of Climatic Seasonality, Energy-Water, and Physical Tolerance Variables.
Climate change is one of the most prominent factors influencing the spatial distribution of plants in China, including gymnosperms. Climatic factors influence gymnosperm distribution along elevational gradients on the Qinghai-Xizang (Tibet) Plateau (QTP), and understanding how species adapt to these factors is important for identifying the impacts of global climate change. For the first time, we examined the county-level distribution of gymnosperm species on QTP using data from field surveys, published works, monographs, and internet sources. We used simulated distribution data of gymnosperms (N = 79) along the elevational gradients to investigate the overall impact of environmental variables in explaining the richness pattern of gymnosperms. Eighteen environmental variables were classified into three key variable sets (climatic seasonality, energy-water, and physical tolerance). We employed principal component analysis and generalized linear models to assess the impact of climatic variables on the gymnosperm's richness pattern. Gymnosperm species are unevenly distributed across the plateau and decline gradually from the southeast to the northwest. The altitudinal gradients have a unimodal relationship with the richness of gymnosperms, with the maximum species richness at an elevation of 3200 m. The joint effects of physical tolerance and energy-water predictors have explained the highest diversity of gymnosperms at mid-elevation. Because the richness peak correlates significantly with the wettest month's precipitation and moisture index, this confirms the significance of moisture on gymnosperm distributions due to increased precipitation during the wet season. Furthermore, our results provide evidence that climatic seasonality factors are involved in the decline of gymnosperm richness at high elevations. A total of 37% of gymnosperm species on QTP are listed as vulnerable, nearly threatened, or endangered, with elevations ranging from 600 m to 5300 m. As a result, we conclude that gymnosperms are at high risk of extinction because of the current climate fluctuations caused by global climate change. Our research offers fundamental data for the study and protection of gymnosperm species along the steepest elevation gradients.
PubMed: 38068701
DOI: 10.3390/plants12234066 -
Heliyon Nov 2023The synthesis, characterization, optimization and oxidation stability improvement of biodiesel from the seed oil of using a novel nano-heterogeneous bio-catalyst...
The synthesis, characterization, optimization and oxidation stability improvement of biodiesel from the seed oil of using a novel nano-heterogeneous bio-catalyst derived from the seed coat (CASC) is reported. The heterogeneous catalyst was produced by calcination and activation at 400 °C, 600 °C and 800 °C using acetic acid. The catalyst was characterized using scanning electron monograph (SEM), Fourier transform infrared (FTIR), and x-ray diffraction (XRD). The seed oil was extracted using mechanical press milling and the biodiesel produced were characterized using AOAC 2019 edition and ASTM D-6151, Fourier transform infrared (FTIR) and gas chromatography (GC) methods. The results indicated that calcined seed coat contains nano-particles and alkaline elements (75 % graphite). The calcination process improved the size reduction and structural arrangement of the particles. The 600 °C calcination temperature had the highest biodiesel yield of 88 % at 3.0 wt % catalyst concentration, 12:1 M ratio of alcohol to oil and 500 rpm. The reusability of catalyst indicated 71.50 % after fifth (5th) cycle. After 28 days storage duration in the presence of the natural, renewable and eco-friendly antioxidant (1 % turmeric), the oxidation instability of the produced biodiesel was reduced by 50 %. The quality of the biodiesel indicates agreement with standards and literature as well as high potential for effective application in diesel engine.
PubMed: 38034711
DOI: 10.1016/j.heliyon.2023.e22006