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Contemporary Clinical Trials... Aug 2024The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with...
BACKGROUND
The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients' experience of participation in a clinical trial and their attitude to the new bottle cap technology.
METHODS
A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis.
RESULTS
Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44-80). Four categories of patients' experiences were identified. consisted of patients' positive attitudes to participation and to be a part of development and research. emphasized the value of the oral information as well as the importance of time for reflection. highlighted the impaired ability to perceive and remember in the acute medical condition. described the overall positive experiences of the smart bottle cap to evaluate adherence.
CONCLUSIONS
Patients' experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.
PubMed: 38947982
DOI: 10.1016/j.conctc.2024.101307 -
World Journal of Transplantation Jun 2024The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel,...
The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel, and uterine transplants. However, the outcomes of transplants are improving (organ survival > 90% after the 1 year). Therefore, there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen. Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems. The perioperative regulation of immunosuppression, the treatment of accompanying problems of immunosuppression, the administration of cortisol and, above all, the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients. The perioperative assessment and preparation includes evaluation of the patient's cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis, or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes. Immunosuppression in transplant patients is associated with the use of calcineurin inhibitors, corticosteroids, and antiproliferation agents. Many times, the clinical picture is atypical, resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality. Multidetector computed tomography is of utmost importance for early diagnosis and management. Transplant recipients are prone to infections, especially specific infections caused by cytomegalovirus and , and they are predisposed to intraoperative or postoperative complications that require great care and vigilance. It is necessary to follow evidence-based therapeutic protocols. Thus, it is required that the clinician choose the correct therapeutic plan for the patient (conservative, emergency open surgery or minimally invasive surgery, including laparoscopic or even robotic surgery).
PubMed: 38947966
DOI: 10.5500/wjt.v14.i2.93944 -
ArXiv Jun 2024Molecular and genomic technological advancements have greatly enhanced our understanding of biological processes by allowing us to quantify key biological variables such...
Molecular and genomic technological advancements have greatly enhanced our understanding of biological processes by allowing us to quantify key biological variables such as gene expression, protein levels, and microbiome compositions. These breakthroughs have enabled us to achieve increasingly higher levels of resolution in our measurements, exemplified by our ability to comprehensively profile biological information at the single-cell level. However, the analysis of such data faces several critical challenges: limited number of individuals, non-normality, potential dropouts, outliers, and repeated measurements from the same individual. In this article, we propose a novel method, which we call U-statistic based latent variable (ULV). Our proposed method takes advantage of the robustness of rank-based statistics and exploits the statistical efficiency of parametric methods for small sample sizes. It is a computationally feasible framework that addresses all the issues mentioned above simultaneously. An additional advantage of ULV is its flexibility in modeling various types of single-cell data, including both RNA and protein abundance. The usefulness of our method is demonstrated in two studies: a single-cell proteomics study of acute myelogenous leukemia (AML) and a single-cell RNA study of COVID-19 symptoms. In the AML study, ULV successfully identified differentially expressed proteins that would have been missed by the pseudobulk version of the Wilcoxon rank-sum test. In the COVID-19 study, ULV identified genes associated with covariates such as age and gender, and genes that would be missed without adjusting for covariates. The differentially expressed genes identified by our method are less biased toward genes with high expression levels. Furthermore, ULV identified additional gene pathways likely contributing to the mechanisms of COVID-19 severity.
PubMed: 38947924
DOI: No ID Found -
ArXiv Jun 2024Single-cell datasets often lack individual cell labels, making it challenging to identify cells associated with disease. To address this, we introduce Mixture Modeling...
Single-cell datasets often lack individual cell labels, making it challenging to identify cells associated with disease. To address this, we introduce Mixture Modeling for Multiple Instance Learning (MMIL), an expectation maximization method that enables the training and calibration of cell-level classifiers using patient-level labels. Our approach can be used to train e.g. lasso logistic regression models, gradient boosted trees, and neural networks. When applied to clinically-annotated, primary patient samples in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), our method accurately identifies cancer cells, generalizes across tissues and treatment timepoints, and selects biologically relevant features. In addition, MMIL is capable of incorporating cell labels into model training when they are known, providing a powerful framework for leveraging both labeled and unlabeled data simultaneously. Mixture Modeling for MIL offers a novel approach for cell classification, with significant potential to advance disease understanding and management, especially in scenarios with unknown gold-standard labels and high dimensionality.
PubMed: 38947923
DOI: No ID Found -
Frontiers in Psychology 2024Swearing, or the use of taboo language, has been repeatedly shown to induce hypoalgesia. While reliable hypoalgesic effects have been observed across studies, the... (Review)
Review
Swearing, or the use of taboo language, has been repeatedly shown to induce hypoalgesia. While reliable hypoalgesic effects have been observed across studies, the mechanisms by which swearing influences pain and the optimal dosage of swearing remain poorly understood. Plausible mechanistic rationale for swearing's impact on pain include sympathetic response, emotion, humor, distraction, aggression, state disinhibition, psychological flow, risky behavior, and self-confidence. It remains unknown how the intensity of the swear word, speech volume, frequency, or timing influences pain modulation. While the majority of evidence demonstrates the efficacy of swearing at attenuating acute pain responses, these studies have utilized healthy populations with controlled experiments in laboratory settings. Comparatively, less is known about how laboratory findings translate practically/clinically to diverse populations, various dosages, and different pain chronicities. A greater understanding of mechanistic underpinnings and practical implications are necessary to feasibly implement swearing as a therapeutic modality to combat pain. The purpose of the following mini-review is to provide an overview of the current evidence on swearing for the reduction of pain, speculate on plausible underlying mechanisms, and discuss the potential for optimization of swearing for real-world translation. Lastly, identifying knowledge gaps to aid in directing future research will be discussed.
PubMed: 38947907
DOI: 10.3389/fpsyg.2024.1416041 -
Nature Cardiovascular Research Oct 2023Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on...
Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on inflammatory populations of monocytes and macrophages that contribute to the development and progression of heart failure. Here, we evaluated a peptide-based imaging probe (Cu-DOTA-ECL1i) that specifically recognizes CCR2 monocytes and macrophages for human cardiac imaging. Compared to healthy controls, Cu-DOTA-ECL1i heart uptake was increased in subjects following acute myocardial infarction, predominately localized within the infarct area, and was associated with impaired myocardial wall motion. These findings establish the feasibility of molecular imaging of CCR2 expression to visualize inflammatory monocytes and macrophages in the injured human heart.
PubMed: 38947883
DOI: No ID Found -
Current Therapeutic Research, Clinical... 2024The Kingdom of Bahrain has reported more than 696,000 cases of coronavirus disease 2019 (COVID-19) and 1548 associated deaths as of December 26, 2022. (Review)
Review
BACKGROUND
The Kingdom of Bahrain has reported more than 696,000 cases of coronavirus disease 2019 (COVID-19) and 1548 associated deaths as of December 26, 2022.
OBJECTIVES
To better inform responses to future public health threats, this narrative review documents the challenges and responses to the COVID-19 pandemic in the Kingdom of Bahrain.
METHODS
A PubMed search was conducted focusing on severe acute respiratory syndrome or COVID-19 in Bahrain. Additional relevant references were also included from the authors' personal reference collections.
RESULTS
The search indicated that Bahrain achieved well-established control of the pandemic through robust public health measures, including an early, comprehensive vaccination program. Bahrain was among the first countries to grant emergency authorization for COVID-19 vaccines; as of December 2022, nearly 73% of the eligible population has been fully vaccinated, and approximately 60% has been boosted. Low case rates in recent months highlight Bahrain's successful response to the COVID-19 pandemic.
CONCLUSIONS
Early organization, robust and systematic protective measures, and a comprehensive vaccination program were key components of the Kingdom's response to the pandemic; traveler quarantines and attempts to combat misinformation were of little or no benefit. These lessons provide guidance for future preparedness to minimize the public health impacts of another pandemic. (. 2024; XX:XXX-XXX).
PubMed: 38947880
DOI: 10.1016/j.curtheres.2024.100733 -
Journal of Extracellular Biology Jul 2024Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a...
Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a transcriptional cascade culminating in the differential expression of target proteins. These differentially expressed proteins can then be packaged into extracellular vesicles (EVs), a form of cellular communication, further propagating the neuroinflammatory response over long distances. Despite this, the EV proteome in the brain, following LPS treatment, has not been investigated. Brain tissue and brain derived EVs (BDEVs) isolated from the cortex of LPS-treated mice underwent thorough characterisation to meet the minimal information for studies of extracellular vesicles guidelines before undergoing mass spectrometry analysis to identify the differentially expressed proteins. Fourteen differentially expressed proteins were identified in the LPS brain tissue samples compared to the controls and 57 were identified in the BDEVs isolated from the LPS treated mice compared to the controls. This included proteins associated with the initiation of the inflammatory response, epigenetic regulation, and metabolism. These results allude to a potential link between small EV cargo and early inflammatory signalling.
PubMed: 38947878
DOI: 10.1002/jex2.165 -
Journal of Clinical Orthopaedics and... Jun 2024Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative...
BACKGROUND
Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative hospital survival rate. By identifying the risk factors leading to early mortality in cervical spine trauma patients, the prognosis of patients with TCSCI can be better predicted.
OBJECTIVE
The study aims to analyze the variables influencing in-hospital mortality in cervical spine trauma patients treated at a Level I trauma Center.
METHODS
Prospective study was conducted on subaxial cervical spine injuries from July 2019 to March 2022. Patients were divided into two groups: Group A, with in-hospital mortality, and Group B, who got discharged from hospital, and mortality predictors were reviewed and analyzed for as potential risk factors for in-hospital mortality.
RESULTS
Out of 105 patients, 83.8 % were male with mean age of 40.43 ± 12.62 years. On univariate analysis, AIS (p-value: <0.01), ICU stay (p-value: <0.01), level of injury (p-value: <0.01), and MRI parameters like the extent of Parenchymal damage (p-value: <0.01), MSCC (p-value: <0.01), and MCC (p-value: <0.01) were potential risk factors for in-hospital mortality. On multivariate regression analysis AIS at presentation (p-value: 0.02) was the only significant independent parameter for in-hospital mortality.
CONCLUSIONS
AIS grading at presentation, duration of ICU stay, level of injury, rate of tracheostomy, and MRI parameters like the extent of parenchymal damage, MCC, and MSCC influence and predicts in-hospital mortality, whereas AIS is the only independent risk factor.
PubMed: 38947859
DOI: 10.1016/j.jcot.2024.102440 -
ACS Omega Jun 2024has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the...
has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH, ABTS, and OH were used to assess its antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS and OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1β, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of leaves in curing inflammatory diseases.
PubMed: 38947843
DOI: 10.1021/acsomega.3c10269