There is limited evidence on the efficacy of hemostatic powders in the management of upper gastrointestinal bleeding.
Provide a pooled estimate of the efficacy and safety profile of hemostatic ...powders in digestive endoscopy.
A computerized bibliographic search on the main databases was performed through December 2018. Pooled effects were calculated using a random-effects model. The primary outcome was immediate hemostasis rate. Secondary outcomes were rebleeding rate (either at 7 and 30 days), bleeding-related mortality, and all-cause mortality rate.
A total of 24 studies, of which three were randomized-controlled trials, with 1063 patients were included in the meta-analysis. Immediate hemostasis was achieved in 95.3% (93.3%–97.3%) of patients, with no difference based on treatment strategy, hemostatic agent used, bleeding etiology. Success rate was slightly lower in spurting bleeding (91.9%). Hemostatic powders showed similar efficacy as compared to conventional endoscopic therapy (odds ratio: 0.84, 0.06–11.47; p = 0.9). Thirty-day rebleeding rate was 16.9% (9.8%–24%) with no difference in comparison to other endoscopic treatments (odds ratio 1.59, 0.35–7.21; p = 0.55). All-cause and bleeding-related mortality rates were 7.6% (4%–10.8%) and 1.4% (0.5%–2.4%), respectively.
Novel hemostatic powders represent a user-friendly and effective tool in the management of upper gastrointestinal bleeding.
The application of graph analysis methods to the topological organization of brain connectivity has been a useful tool in the characterization of brain related disorders. However, the availability of ...tools, which enable researchers to investigate functional brain networks, is still a major challenge. Most of the studies evaluating brain images are based on centrality and segregation measurements of complex networks. In this study, we applied the concept of graph spectral entropy (GSE) to quantify the complexity in the organization of brain networks. In addition, to enhance interpretability, we also combined graph spectral clustering to investigate the topological organization of sub-network's modules. We illustrate the usefulness of the proposed approach by comparing brain networks between attention deficit hyperactivity disorder (ADHD) patients and the brain networks of typical developing (TD) controls. The main findings highlighted that GSE involving sub-networks comprising the areas mostly bilateral pre and post central cortex, superior temporal gyrus, and inferior frontal gyri were statistically different (p-value=0.002) between ADHD patients and TD controls. In the same conditions, the other conventional graph descriptors (betweenness centrality, clustering coefficient, and shortest path length) commonly used to identify connectivity abnormalities did not show statistical significant difference. We conclude that analysis of topological organization of brain sub-networks based on GSE can identify networks between brain regions previously unobserved to be in association with ADHD.
•We developed a framework to identify brain regions that are related to disorders.•We applied comparisons among standard descriptive measures and the proposed measure.•We were able to identify brain regions that might be related to ADHD.•Results indicate our method is useful to investigate neuronal network abnormalities.
Synapse deterioration underlying severe memory loss in early Alzheimer's disease (AD) is thought to be caused by soluble amyloid beta (Aβ) oligomers. Mechanistically, soluble Aβ oligomers, also ...referred to as Aβ-derived diffusible ligands (ADDLs), act as highly specific pathogenic ligands, binding to sites localized at particular synapses. This binding triggers oxidative stress, loss of synaptic spines, and ectopic redistribution of receptors critical to plasticity and memory. We report here the existence of a protective mechanism that naturally shields synapses against ADDL-induced deterioration. Synapse pathology was investigated in mature cultures of hippocampal neurons. Before spine loss, ADDLs caused major downregulation of plasma membrane insulin receptors (IRs), via a mechanism sensitive to calcium calmodulin-dependent kinase II (CaMKII) and casein kinase II (CK2) inhibition. Most significantly, this loss of surface IRs, and ADDL-induced oxidative stress and synaptic spine deterioration, could be completely prevented by insulin. At submaximal insulin doses, protection was potentiated by rosiglitazone, an insulin-sensitizing drug used to treat type 2 diabetes. The mechanism of insulin protection entailed a marked reduction in pathogenic ADDL binding. Surprisingly, insulin failed to block ADDL binding when IR tyrosine kinase activity was inhibited; in fact, a significant increase in binding was caused by IR inhibition. The protective role of insulin thus derives from IR signaling-dependent downregulation of ADDL binding sites rather than ligand competition. The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis.
Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is ...the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i) interesting physiological property of C. neoformans regarding its amino acid uptake system; (ii) an important aspect of virulence, which is the need for amino acid permeases during thermal and oxidative stress resistance and, hence, host invasion and colonization; and (iii) provides a convenient prototype for antifungal development, which are the amino acid permeases Aap4/Aap5 and their inhibitor.
Object location task (OLT) has been used as a model of hippocampal-dependent memory. Despite this application, there is neither a consistent pharmacological validation of NMDA receptor modulation nor ...an evaluation of hippocampal participation in mice. In the OLT, mice were placed in the open field with two identical objects for 3
min and, after a delay of 30, 90, 180 or 360
min, one object was moved to a new location and the time spent exploring the objects in new, (novel) and old (familiar) locations was recorded. Our results showed that the mice were able to discriminate object location when tested either 90 or 180
min after training. Intraperitoneal administration of MK801 (NMDA receptors antagonist) or scopolamine (mACh antagonist) induced amnesic effects. On the other hand,
d-cycloserine (NMDA agonist) or tacrine (cholinesterase inhibitor) were able to improve memory in the mice tested. In addition, lidocaine infusion in the hippocampal CA1 region 10
min before training blocked object location memory. In short, this work indicates that OLT is susceptible to modulation of NMDA receptors, cholinergic neurotransmission and it is the first to characterize the participation of the hippocampal CA1 region, in this task.
•HRV is used to assess cardiac autonomic modulation.•HRV is useful to assess the effect of physical exercise programmes.•What are the common shortcomings of using the HRV methodology?•What are the ...recommendations of using HRV collection and analysis methods?•Checklist regarding the use of the HRV collection and analysis methodology.
Heart rate variability is used as an assessment method for cardiac autonomic modulation. Since the Task Force's publication on heart rate variability in 1996, the European Heart Rhythm Association Position Paper in 2015 and a recent publication in 2017, attention has been paid to recommendations on using heart rate variability analysis methods, as well as their applications in different physiological conditions and clinical studies. This analysis has proved to be useful as a complementary tool for clinical evaluation and to assess the effect of non-pharmacological therapeutic interventions, such as physical exercise programmes, on cardiac autonomic modulation.
The aim of this article is to make recommendations and to develop a checklist of normalisation procedures regarding the use of heart rate variability data collection and analysis methodology, focusing on the cardiology area and cardiac rehabilitation.
Based on previous heart rate variability publications, this paper provides a description of the most common shortcomings of using the analysis methods and considers recommendations and suggestions on how to minimise these occurrences by using a specific checklist.
This article includes recommendations and a checklist regarding the use of heart rate variability collection and analysis methods. This work could help improve reporting on clinical evaluation and therapeutic intervention results and consequently, disseminate heart rate variability knowledge.
Coronary artery disease (CAD), the most common manifestation of cardiovascular disease, remains the most common cause of mortality in the United States. Risk assessment is key for primary prevention ...of coronary events and coronary artery calcium (CAC) scoring using computed tomography (CT) is one such non-invasive tool. Despite the proven clinical value of CAC, the current clinical practice implementation for CAC has limitations such as the lack of insurance coverage for the test, need for capital-intensive CT machines, specialized imaging protocols, and accredited 3D imaging labs for analysis (including personnel and software). Perhaps the greatest gap is the millions of patients who undergo routine chest CT exams and demonstrate coronary artery calcification, but their presence is not often reported or quantitation is not feasible. We present two deep learning models that automate CAC scoring demonstrating advantages in automated scoring for both dedicated gated coronary CT exams and routine non-gated chest CTs performed for other reasons to allow opportunistic screening. First, we trained a gated coronary CT model for CAC scoring that showed near perfect agreement (mean difference in scores = -2.86; Cohen's Kappa = 0.89, P < 0.0001) with current conventional manual scoring on a retrospective dataset of 79 patients and was found to perform the task faster (average time for automated CAC scoring using a graphics processing unit (GPU) was 3.5 ± 2.1 s vs. 261 s for manual scoring) in a prospective trial of 55 patients with little difference in scores compared to three technologists (mean difference in scores = 3.24, 5.12, and 5.48, respectively). Then using CAC scores from paired gated coronary CT as a reference standard, we trained a deep learning model on our internal data and a cohort from the Multi-Ethnic Study of Atherosclerosis (MESA) study (total training n = 341, Stanford test n = 42, MESA test n = 46) to perform CAC scoring on routine non-gated chest CT exams with validation on external datasets (total n = 303) obtained from four geographically disparate health systems. On identifying patients with any CAC (i.e., CAC ≥ 1), sensitivity and PPV was high across all datasets (ranges: 80-100% and 87-100%, respectively). For CAC ≥ 100 on routine non-gated chest CTs, which is the latest recommended threshold to initiate statin therapy, our model showed sensitivities of 71-94% and positive predictive values in the range of 88-100% across all the sites. Adoption of this model could allow more patients to be screened with CAC scoring, potentially allowing opportunistic early preventive interventions.
Morphological analysis is the standard method of assessing embryo quality; however, its inherent subjectivity tends to generate discrepancies among evaluators. Using genetic algorithms and artificial ...neural networks (ANNs), we developed a new method for embryo analysis that is more robust and reliable than standard methods. Bovine blastocysts produced in vitro were classified as grade 1 (excellent or good), 2 (fair), or 3 (poor) by three experienced embryologists according to the International Embryo Technology Society (IETS) standard. The images (n = 482) were subjected to automatic feature extraction, and the results were used as input for a supervised learning process. One part of the dataset (15%) was used for a blind test posterior to the fitting, for which the system had an accuracy of 76.4%. Interestingly, when the same embryologists evaluated a sub-sample (10%) of the dataset, there was only 54.0% agreement with the standard (mode for grades). However, when using the ANN to assess this sub-sample, there was 87.5% agreement with the modal values obtained by the evaluators. The presented methodology is covered by National Institute of Industrial Property (INPI) and World Intellectual Property Organization (WIPO) patents and is currently undergoing a commercial evaluation of its feasibility.
The infodemic accompanying the COVID-19 pandemic has led to an overwhelming amount of information, including questions, concerns and misinformation. Pandemic fatigue has been identified as a concern ...from early in the pandemic. With new and ongoing health emergencies in 2022, it is important to understand how pandemic fatigue is being discussed and expressed by users on digital channels. This study aims to explore and report on key narrative themes associated with expressions of pandemic fatigue by users on digital platforms.
This paper describes the collection of publicly available data over a 3-month period from multiple online sources using the Meltwater and CrowdTangle platforms to source data from Twitter, Facebook, Instagram, YouTube, TikTok, Pinterest, Product Reviews, Twitch, blogs & forums. A comprehensive search strategy was developed and tested. A total of 1,484,042 social media posts were identified during the time-period that included the defined search terms for pandemic fatigue. These data were initially sorted by highest levels of engagement and from this dataset, analysts reviewed the identified posts to isolate and remove irrelevant content and identify dominant narratives. A thematic analysis was carried out on these narratives to identify themes related to expression of pandemic fatigue. Two researchers reviewed the data and themes.
The thematic analysis of narratives identified six main themes relating to expression of pandemic fatigue, and one theme of counter narratives against pandemic fatigue. Data volume increased concurrent with the time of the mpox emergency announcement. Emergent themes showed the different ways users expressed pandemic fatigue and how it was interlaced with issues of trust, preventative measure acceptance and uptake, misinformation, and being overwhelmed with multiple or sustained emergencies.
This paper has identified the different ways users express pandemic fatigue on digital channels over a 3-month period. Better understanding the implications of the information environment on user's perceptions, questions, and concerns regarding pandemic and more broadly emergency fatigue is vital in identifying relevant interventions and, in the longer term, strengthening the global architecture for health emergency preparedness, prevention, readiness and resilience, as evidenced in this paper. There are clear pathways for further research, including incorporating additional languages and reviewing these themes over longer time periods.
Strategies to prolong homeostasis of ex vivo perfused lungs Takahashi, Mamoru; Andrew Cheung, Hei Yu; Watanabe, Tatsuaki ...
The Journal of thoracic and cardiovascular surgery,
June 2021, 2021-Jun, 2021-06-00, 20210601, Letnik:
161, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Ex vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto ex vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A ...longer ex vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic ex vivo lung perfusion.
We systematically examined 3 modifications of ex vivo lung perfusion perfusate administration in a large animal 24-hour ex vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of ex vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate.
Only 1 lung in the control group completed 24-hour ex vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P = .03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control.
Modifications of ex vivo lung perfusion perfusate toward achieving a stable homeostatic state can extend perfusion time for up to 24 hours. Although these modifications allow for prolonged ex vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours.
Three modifications of EVLP perfusate administration in a pig 24-hour EVLP model. The TPN group achieved significantly longer stable perfusion time compared with control (P = .03). The dotted lines represent 95% confidence interval. Display omitted
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