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Though bioaccumulation of pharmaceuticals by aquatic organisms continues to receive scientific attention, the internal disposition of these contaminants among different tissue compartments of fish species has been infrequently investigated, particularly among fish at different trophic positions. We tested a human to fish biological read-across hypothesis for contaminant disposition by examining tissue-specific accumulation in three understudied species, longnose gar (Lepisosteus osseus; piscivore), gizzard shad (Dorosoma cepedianum; planktivore/detritivore), and smallmouth buffalo (Ictiobus bubalus; benthivore), from a river influenced by municipal effluent discharge. In addition to surface water, fish plasma, and brain, gill, gonad, liver, and lateral muscle fillet tissues were analyzed via isotope dilution liquid chromatography tandem mass spectrometry. Caffeine and sucralose, two common effluent tracers, were quantitated at low micrograms per liter levels in surface water, while an anticonvulsant, carbamazepine, was observed at levels up to 37 ng/L. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and primary metabolites were detected in at least one tissue of all three species at low micrograms per kilogram concentrations. Within each species, brain and liver of select fish contained the highest levels of SSRIs compared to plasma and other tissues, which is generally consistent with human tissue disposition patterns. However, we observed differential accumulation among specific tissue types and species. For example, mean levels of sertraline in brain and liver tissues were 13.4 µg/kg and 1.5 µg/kg in gizzard shad and 1.3 µg/kg and 7.3 µg/kg in longnose gar, respectively. In contrast, smallmouth buffalo did not consistently accumulate SSRIs to detectable levels. Tissue-specific eco-exposome efforts are necessary to understand mechanisms associated with such marked bioaccumulation and internal dispositional differences among freshwater fish species occupying different trophic positions. Environ Toxicol Chem 2024;43:1894-1902. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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Peixes , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacocinética , Peixes/metabolismo , Bioacumulação , Distribuição Tecidual , Carbamazepina/metabolismo , Carbamazepina/farmacocinética , Sacarose/metabolismo , Sacarose/análogos & derivados , Cafeína/metabolismo , Cafeína/farmacocinética , Fígado/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Brânquias/metabolismo , Monitoramento Ambiental , Rios/química , Cadeia Alimentar , Fluoxetina/análogos & derivados , Fluoxetina/metabolismo , Fluoxetina/farmacocinética , Preparações Farmacêuticas/metabolismo , Encéfalo/metabolismoRESUMO
An initial cross of V. darrowii 'Johnblue' (Darrow's blueberry) × V. vitis-idaea 'Red Sunset' (lingonberry) produced more than 30 true intersectional diploid hybrids as confirmed by molecular markers. The most vigorous of these hybrids was extensively evaluated. This hybrid, US 2535-A, was floriferous and morphologically intermediate to the respective parents. Examination of pollen suggested low male fertility. Numerous crosses using the hybrid as a female reflected similarly low fertility and potential crossing barriers. Stylar examination suggested blockage of pollen tube growth in self-pollinations and significantly retarded growth in backcross pollinations. Nonetheless, two confirmed hybrid offspring were produced using the F1 hybrid as a female in crosses with V. vitis-idaea and V. darrowii, respectively. In a second set of crosses utilizing additional V. darrowii and V. vitis-idaea genotypes, another 23 verified hybrids in seven parental combinations were produced. Hybrids such as the ones presented offer the potential for generating de novo interspecific fruit types in blueberry and/or broadening the adaptation of lingonberry.
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BACKGROUND: Heart failure requires complex management, and increased patient knowledge has been shown to improve outcomes. This study assessed the knowledge of Chat Generative Pre-trained Transformer (ChatGPT) and its appropriateness as a supplemental resource of information for patients with heart failure. METHOD: A total of 107 frequently asked heart failure-related questions were included in 3 categories: "basic knowledge" (49), "management" (41) and "other" (17). Two responses per question were generated using both GPT-3.5 and GPT-4 (i.e., two responses per question per model). The accuracy and reproducibility of responses were graded by two reviewers, board-certified in cardiology, with differences resolved by a third reviewer, board-certified in cardiology and advanced heart failure. Accuracy was graded using a four-point scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. RESULTS: GPT-4 provided 107/107 (100%) responses with correct information. Further, GPT-4 displayed a greater proportion of comprehensive knowledge for the categories of "basic knowledge" and "management" (89.8% and 82.9%, respectively). For GPT-3, there were two total responses (1.9%) graded as "some correct and incorrect" for GPT-3.5, while no "completely incorrect" responses were produced. With respect to comprehensive knowledge, GPT-3.5 performed best in the "management" category and "other" category (prognosis, procedures, and support) (78.1%, 94.1%). The models also provided highly reproducible responses, with GPT-3.5 scoring above 94% in every category and GPT-4 with 100% for all answers. CONCLUSIONS: GPT-3.5 and GPT-4 answered the majority of heart failure-related questions accurately and reliably. If validated in future studies, ChatGPT may serve as a useful tool in the future by providing accessible health-related information and education to patients living with heart failure. In its current state, ChatGPT necessitates further rigorous testing and validation to ensure patient safety and equity across all patient demographics.
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BACKGROUND: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients. OBJECTIVE: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis. METHODS: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing). RESULTS: ChatGPT-4 (n=98) provided 93 (95%) responses with accurate information, and 82 (84%) were comprehensive. ChatGPT-3.5 (n=83) provided 74 (89%) responses with accurate information, and 66 (79%) were comprehensive. When examined by question category, ChatGTP-4 and ChatGPT-3.5 provided 53 (95%) and 48 (86%) comprehensive responses, respectively, to "general questions" (n=56). When examined by subject, ChatGPT-4 and ChatGPT-3.5 performed best in response to cardiology questions (n=12) with both models producing 10 (83%) comprehensive responses. For gastroenterology (n=15), ChatGPT-4 received comprehensive grades for 9 (60%) responses, and ChatGPT-3.5 provided 8 (53%) responses. Overall, 96 of 98 (98%) responses for ChatGPT-4 and 73 of 83 (88%) for ChatGPT-3.5 were reproducible. The readability of ChatGPT-4's responses ranged from 10th to beyond graduate US grade levels with an average of 15.5 (SD 1.9). CONCLUSIONS: Large language models are a promising tool for accurate and reliable health information for patients living with amyloidosis. However, ChatGPT's responses exceeded the American Medical Association's recommended fifth- to sixth-grade reading level. Future studies focusing on improving response accuracy and readability are warranted. Prior to widespread implementation, the technology's limitations and ethical implications must be further explored to ensure patient safety and equitable implementation.
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The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.
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Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Animais , Camundongos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Acetatos/farmacologia , Acetatos/metabolismo , Neoplasias Pancreáticas/genética , Poliaminas , Microambiente TumoralRESUMO
BACKGROUND: There is limited understanding of how risk perceptions changed as the US population gained experience with COVID-19. The objectives were to examine risk perceptions and determine the factors associated with risk perceptions and how these changed over the first 18 mo of the pandemic. METHODS: Seven cross-sectional online surveys were fielded between May 2020 and October 2021. The study included a population-weighted sample of 138,303 US adults drawn from a market research platform, with an average 68% cooperation rate. Respondents' risk perception of developing COVID in the next 30 days was assessed at each time point. We examined relationships between 30-day risk perceptions and various factors (including sociodemographic features, health, COVID-19 experience, political affiliation, and psychological variables). RESULTS: COVID risk perceptions were stable across the 2020 surveys and showed a significant decrease in the 2021 surveys. Several factors, including older age, worse health, high COVID worry, in-person employment type, higher income, Democratic political party affiliation (the relatively more liberal party in the United States), low tolerance of uncertainty, and high anxiety were strongly associated with higher 30-d risk perceptions in 2020. One notable change occurred in 2021, in that younger adults (aged 18-29 y) had significantly higher 30-d risk perceptions than older adults did (aged 65 y and older) after vaccination. Initial differences in perception by political party attenuated over time. Higher 30-d risk perceptions were significantly associated with engaging in preventive behaviors. LIMITATIONS: Cross-sectional samples, risk perception item focused on incidence not severity. CONCLUSIONS: COVID risk perceptions decreased over time. Understanding the longitudinal pattern of risk perceptions and the factors associated with 30-d risk perceptions over time provides valuable insights to guide public health communication campaigns. HIGHLIGHTS: The study assessed COVID-19 risk perceptions at 7 time points over 18 mo of the pandemic in large samples of US adults.Risk perceptions were fairly stable until the introduction of vaccines in early 2021, at which point they showed a marked reduction.Higher COVID-19 30-d risk perceptions were significantly associated with the preventive behaviors of masking, limiting social contact, avoiding restaurants, and not entertaining visitors at home.
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COVID-19 , Humanos , Estados Unidos/epidemiologia , Idoso , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC. SIGNIFICANCE: The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models. This article is featured in Selected Articles from This Issue, p. 5.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Vitamina B 6 , Microambiente Tumoral , Células Matadoras Naturais , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , CarbonoRESUMO
Nutrient contamination from point and non-point sources can lead to harmful consequences, such as algal blooms. Point and non-point nutrient loading estimation is determined using modeling approaches and often require an abundance of variables and observations for calibration. Small rural streams that lack water use designations often lack available data to utilize current modeling strategies. This study proposes the use of a 3-phase hybrid stepwise statistical modeling approach using generalized linear mixed models (GLMM) and a reference stream. Two streams in Central Texas were sampled for 13 months between February 2020 and February 2021, one being impacted by a wastewater treatment plant (WWTP). Dissolved phosphorus (PO4-P), ammonia (NH3-N), nitrite/nitrate (NO2 + NO3-N), total nitrogen (TN), and total phosphorus (TP) were sampled in both streams for each month. Non-point sources of contamination, such as land use/land cover and geomorphology composition, were quantified for both sub-basin drainage areas. Phase I models predicted nutrient concentrations in the reference stream using non-point source variables along with discharge and temporal variables. Best fit models were carried forward to phase II and leveraged a point-source variable, which is a naïve estimate of effluent nutrient concentration in the absence of assimilation. Phase II model coefficients highlight the significance of point-source contamination in predicting nutrient concentration, but overall lacked the ability to make future predictions under new hydrologic regimes from WWTP intensification. Phase III models included deterministically calculating an uptake variable using the relationship between discharge and wetted widths, predicting background non-point concentrations by leveraging phase I models, and calculating future nutrient loadings from WWTP intensification. This approach predicted significant increases in nutrient concentrations under planned WWTP intensification scenarios and decreased uptake efficiencies under the new hydrologic regimes.
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Águas Residuárias , Poluentes Químicos da Água , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Modelos Estatísticos , Fósforo/análise , Nutrientes , Nitrogênio/análiseRESUMO
BACKGROUND: Mitral valve stenosis can be a highly symptomatic condition with significant complications if left untreated. In such cases, mitral valve replacement with a bioprosthetic or mechanical valve may be a viable solution to prevent progressive disease. Current guidelines do not recommend continued anticoagulation beyond 6 months for patients who have undergone bioprosthetic valve replacement without a separate indication for anticoagulation. With this case discussion we aim to 1) Review the current indications for anticoagulation for bioprosthetic mitral valves in patients without atrial fibrillation and 2) Discuss the constellation of comorbidities that may affect the decision to begin anticoagulation therapy. CASE PRESENTATION: We present a case describing a 55-year-old male with end-stage renal disease, coronary artery disease with coronary artery bypass graft surgery, and bioprosthetic mitral valve replacement 2 years prior with rapid degeneration of the replaced valve and on warfarin without a clear indication for anticoagulation. The patient was admitted for symptomatic, severe mitral stenosis and consideration of transcatheter mitral valve-in-valve replacement. During hospital admission, warfarin was discontinued and replaced with prophylactic anticoagulation. However, 8 days after warfarin cessation an intraoperative transesophageal echocardiography revealed a newly developed large left atrial thrombus leading to cancellation of the planned operation. CONCLUSIONS: This patient developed a left atrial thrombus after discontinuing warfarin in the setting of rapidly deteriorating bioprosthetic valve stenosis and vascular comorbidities. The decision to discontinue warfarin was made in concordance with current guidelines, which do not indicate systemic anticoagulation post 3-6 months after bioprosthetic valve replacement without separate indication for anticoagulation. This case identifies the need to investigate rebound hypercoagulability and further risk stratify comorbidities which may independently increase the risk of clot formation in the setting of severe mitral valve stenosis.
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Bioprótese , Próteses Valvulares Cardíacas , Estenose da Valva Mitral , Trombose , Humanos , Masculino , Pessoa de Meia-Idade , Anticoagulantes/efeitos adversos , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/prevenção & controle , Varfarina/efeitos adversosRESUMO
Introduction: We now recognize that plant genotype affects the assembly of its microbiome, which in turn, affects essential plant functions. The production system for crop plants also influences the microbiome composition, and as a result, we would expect to find differences between conventional and organic production systems. Plant genotypes selected in an organic regime may host different microbiome assemblages than those selected in conventional environments. We aimed to address these questions using recombinant inbred populations of snap bean that differed in breeding history. Methods: Rhizosphere microbiomes of conventional and organic common beans (Phaseolus vulgaris L.) were characterized within a long-term organic research site. The fungal and bacterial communities were distinguished using pooled replications of 16S and ITS amplicon sequences, which originated from rhizosphere samples collected between flowering and pod set. Results: Bacterial communities significantly varied between organic and conventional breeding histories, while fungal communities varied between breeding histories and parentage. Within the organically-bred populations, a higher abundance of a plant-growth-promoting bacteria, Arthrobacter pokkalii, was identified. Conventionally-bred beans hosted a higher abundance of nitrogen-fixing bacteria that normally do not form functional nodules with common beans. Fungal communities in the organically derived beans included more arbuscular mycorrhizae, as well as several plant pathogens. Discussion: The results confirm that the breeding environment of crops can significantly alter the microbiome community composition of progeny. Characterizing changes in microbiome communities and the plant genes instrumental to these changes will provide essential information about how future breeding efforts may pursue microbiome manipulation.
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Hop production utilizes exclusively female plants, whereas male plants only serve to generate novel variation within breeding programs through crossing. Currently, hop lacks a rapid and accurate diagnostic marker to determine whether plants are male or female. Without a diagnostic marker, breeding programs may take 1-2 years to determine the sex of new seedlings. Previous research on sex-linked markers was restricted to specific populations or breeding programs and therefore had limited transferability or suffered from low scalability. A large collection of 765 hop genotypes with known sex phenotypes, genotyping-by-sequencing, and genome-wide association mapping revealed a highly significant marker on the sex chromosome (LOD score = 208.7) that predicted sex within our population with 96.2% accuracy. In this study, we developed a PCR allele competitive extension (PACE) assay for the diagnostic SNP and tested three quick DNA extraction methodologies for rapid, high-throughput genotyping. Additionally, the marker was validated in a separate population of 94 individuals from 15 families from the USDA-ARS hop breeding program in Prosser, WA with 96% accuracy. This diagnostic marker is located in a gene predicted to encode the basic helix-loop-helix transcription factor protein, a family of proteins that have been previously implicated in male sterility in a variety of plant species, which may indicate a role in determining hop sex. The marker is diagnostic, accurate, affordable, and highly scalable and has the potential to improve efficiency in hop breeding.
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Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Humanos , Mapeamento Cromossômico , Fenótipo , GenótipoRESUMO
Bipyridines are ubiquitous in organic and inorganic chemistry because of their redox and photochemical properties and their utility as ligands to transition metals. Cationic substituents on bipyridines and azaarenes are valuable as powerful electron-withdrawing functionalities that also enhance solubility in polar solvents, but there are no general methods for direct functionalization. A versatile method for the preparation of trimethylammonium- and triarylphosphonium-substituted bipyridines and azaheterocycles is disclosed. This methodology showcases a C-H activation of pyridine N-oxides that enables a highly modular and scalable synthesis of a diverse array of cationically charged azaarenes. The addition of trimethylammonium functionalities on bipyridine derivatives resulted in more anodic reduction potentials (up to 700 mV) and increased electrochemical reversibility compared to the neutral unfunctionalized bipyridine. Additonally, metallation of 4-triphenylphosphinated biquinoline to make the corresponding Re(CO)3Cl complex resulted in reduction potentials 400 mV more anodic than the neutral derivative.
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Whole-mount in situ hybridization is a critical technique for analyzing gene expression in planarians. While robust in situ protocols have been developed, these protocols are laborious, making them challenging to incorporate in an academic setting, reducing throughput and increasing time to results. Here, the authors systematically tested modifications to all phases of the protocol with the goal of eliminating steps and reducing time without impacting quality. This modified protocol allows for whole-mount colorimetric in situ hybridization and multicolor fluorescence in situ hybridization to be completed in two days with a significant reduction in steps and hands-on processing time.
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Planárias , Animais , Planárias/genética , Hibridização in Situ Fluorescente/métodosRESUMO
BACKGROUND: Many oncology physicians are confronted with the topic of complementary and integrative medicine (CIM) by cancer patients. This study examined whether a blended learning (e-learning and a workshop) to train oncology physicians in providing advice on CIM therapies to their cancer patients, in addition to distributing an information leaflet about reputable CIM websites, had different effects on physician-reported outcomes in regard to consultations compared with only distributing the leaflet. METHODS: In a multicenter, cluster-randomized trial, 48 oncology physicians were randomly allocated to an intervention group (CIM consultation and an information leaflet) or a control group (information leaflet only). After the training, the oncology physicians conducted 297 consultations with their cancer patients. Measurements were assessed at oncology physician, physician-patient-interaction (measured by external reviewers), and patient levels. This analysis focused on the physician outcomes of stress reaction and perceived consultation skill competency. In addition, qualitative interviews were conducted with a subsample of oncology physicians who experienced both, the intervention and control condition. RESULTS: The oncology physicians in the intervention group showed a lower stress reaction in all measured dimensions after CIM consultations than those in the control group. There was no significant difference between oncology physicians in the intervention and control groups regarding the perceived consultation skill competency (overburden: intervention 1.4 [95% CI: 0.7;2.1]; control 2.1 [95% CI: 1.4;2.7], tension: 1.3 [95% CI: 0.7;2.0] vs. 1.9 [95% CI: 1.3;2.5], and discomfort with consultation situations: 1.0 [95% CI: 0.4;1.7]; vs. 1.7 [95% CI: 1.2;2.3]). The qualitative data showed that only providing the leaflet seemed impersonal to oncology physicians, while the training made them feel well prepared to conduct a full conversation about CIM and provide the information leaflet. CONCLUSIONS: In our exploratory study providing structured CIM consultations showed positive effects on the perceived stress of oncology physicians, and the training was subjectively experienced as an approach that improved physician preparation for advising cancer patients about CIM, however no effects regarding perceived consultation skill competency were found. TRIAL REGISTRATION: The trial registration number of the KOKON-KTO study is DRKS00012704 in the German Clinical Trials Register (Date of registration: 28.08.2017).
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Neoplasias , Médicos , Humanos , Oncologia , Comunicação , Confiabilidade dos Dados , Neoplasias/terapiaRESUMO
BACKGROUND: Duplex ultrasound is frequently used to determine the degree of carotid stenosis. However, axial imaging is typically obtained for operative planning for transcarotid artery revascularization (TCAR). We examined if ultrasound alone is sufficient before TCAR. METHODS: Data from the Vascular Quality Initiative TCAR Surveillance Project registry between 2016 and 2021 was obtained. Patients were divided into 2 groups-those with preoperative ultrasound-alone (US) and those with additional axial imaging (AX). Perioperative outcomes were compared utilizing univariate Chi-square, independent t-test, multivariate logistic regression, and Kaplan-Meier analysis. RESULTS: There were 3,418 patients identified: 682 in the US group and 2,736 in the AX group. More preoperative hypertension was reported in US (16.1% vs. 10.2%, P < 0.001) while cardiovascular disease (23% vs. 28.9%, P = 0.006) and prior ipsilateral stroke (22% vs. 32.7%, P = 0.002) were more prevalent in AX. More patients had history of contralateral carotid endarterectomy (13.6% vs. 16.7%, P = 0.035) or either ipsilateral (2.6% vs. 1.2%, P = 0.002) or contralateral (7.9% vs. 4.9%, P = 0.008) carotid artery stenting in the US group. Lower preoperative creatinine was reported in the US cohort (1.09 ± 0.01 vs. 1.18 ± 0.02, P < 0.001) while more were symptomatic in AX (28.2% vs. 36.2%, P < 0.001). There were no significant differences between lesion characteristics or operative decision making. A slightly higher total procedure time was seen in AX (73.7 ± 0.6 vs. 68.6 ± 1.3 min, P = 0.017). No differences were seen in perioperative transient ischemic attack/stroke or other immediate complications. At 2-year follow-up, both groups reported no significant differences in stroke-free survival (P = 0.750) and independent functional status remained near-identical (97.3% vs. 97.4%, P = 0.921). Kaplan-Meier analysis yielded no significant difference between mortality at 2 years (P = 0.563). Bivariate logistic regression modeling did reveal a statistically significant increase in likelihood of long-term ipsilateral stroke (odds ratio 1.77, P = 0.015) and non stroke-related complication in the postoperative period (odds ratio 4.81, P = 0.005). However, only a statistically significant relationship persisted in non-stroke complication when the model was controlled for between-group differences. CONCLUSIONS: No significant differences in postoperative or long-term complications were noted with additional AX in preoperative TCAR planning. Thus, duplex ultrasound offers a safe and effective alternative for those with contraindication or axial imaging.
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Estenose das Carótidas , Endarterectomia das Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Fatores de Tempo , Stents/efeitos adversos , Endarterectomia das Carótidas/efeitos adversos , Artérias , Ultrassonografia Doppler Dupla/efeitos adversos , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Restless legs syndrome (RLS) is a common neurological disease that has a significant impact on daily activities and quality of life, for which there is often no satisfactory therapy. Complementary medicine, such as acupressure and hydrotherapy, is used to treat patients with RLS; however, the clinical evidence is unclear. This study aims to investigate the effects and feasibility of self-administered hydrotherapy and acupressure in patients with RLS. METHODS: This is a randomized, controlled, open-label, exploratory, clinical study with 3 parallel arms, comparing both self-applied hydrotherapy (according to the German non-medical naturopath Sebastian Kneipp) and acupressure in addition to routine care in comparison to routine care alone (waiting list control) in patients with RLS. Fifty-one patients with at least moderate restless-legs syndrome will be randomized. Patients in the hydrotherapy group will be trained in the self-application of cold knee/lower leg affusions twice daily for 6 weeks. The acupressure group will be trained in the self-application of 6-point-acupressure therapy once daily for 6 weeks. Both interventions take approximately 20 minutes daily. The 6-week mandatory study intervention phase, which is in addition to the patient preexisting routine care treatment, is followed by a 6-week follow-up phase with optional interventions. The waitlist group will not receive any study intervention in addition to their routine care before the end of week 12. Outcome parameters including RLS-severity, disease and health-related quality of life (RLS-QoL, SF-12), Hospital Anxiety and Depression Score in German version, general self-efficacy scale, and study intervention safety will be measured at baseline and after 6 and 12 weeks. The statistical analyses will be descriptive and exploratory. CONCLUSION: In the case of clinically relevant therapeutic effects, feasibility, and therapeutic safety, the results will be the basis for planning a future confirmatory randomized trial and for helping to develop further RLS self-treatment concepts.
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Acupressão , Hidroterapia , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/terapia , Qualidade de Vida , Perna (Membro)RESUMO
Freshwater ecosystems are exposed to engineered nanoparticles (NPs) through discharge from wastewater and agricultural runoff. We conducted a 9-month mesocosm experiment to examine the combined effects of chronic NP additions on insect emergence and insect-mediated contaminant flux to riparian spiders. Two NPs (copper, gold, plus controls) were crossed by two levels of nutrients in 18 outdoor mesocosms open to natural insect and spider colonization. We collected adult insects and two riparian spider genera, Tetragnatha and Dolomedes, for 1 week on a monthly basis. We estimated a significant decrease in cumulative insect emergence of 19% and 24% after exposure to copper and gold NPs, irrespective of nutrient level. NP treatments led to elevated copper and gold tissue concentrations in adult insects, which resulted in terrestrial fluxes of metals. These metal fluxes were associated with increased gold and copper tissue concentrations for both spider genera. We also observed about 25% fewer spiders in the NP mesocosms, likely due to reduced insect emergence and/or NP toxicity. These results demonstrate the transfer of NPs from aquatic to terrestrial ecosystems via emergence of aquatic insects and predation by riparian spiders, as well as significant reductions in insect and spider abundance in response to NP additions.