Ετικέτες

Δευτέρα 2 Νοεμβρίου 2020

Extent of arterial calcification by conventional vitamin K antagonist treatment

als.fakia shared this article with you from Inoreader

journal.pone.0241450.g003&size=inline

by Selma Hasific, Kristian Altern Øvrehus, Oke Gerke, Jesper Hallas, Martin Busk, Jess Lambrechtsen, Grazina Urbonaviciene, Niels Peter Rønnow Sand, Jens Steen Nielsen, Louise Diederichsen, Kenneth Bruun Pedersen, Rasmus Carter-Storch, Nivethitha Ilangkovan, Hans Mickley, Lars Melholt Rasmussen, Jes Sandal Lindholt, Axel Diederichsen

Background and aims

Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD).

Methods

We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007–2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1–99, 100–399, ≥400) was investigated by ordered logistic regression adjusting for covariates.

Results

The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009–1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935–1.074). There was no significant interaction between VKA treatment duration and age on CAC category.

Conclusions

Adjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category.

View on the web

Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation

als.fakia shared this article with you from Inoreader

journal.pone.0241139.g012&size=inline

by Daiki Nakashima, Takashi Onuma, Kumiko Tanabe, Yuko Kito, Kodai Uematsu, Daisuke Mizutani, Yukiko Enomoto, Masanori Tsujimoto, Tomoaki Doi, Rie Matsushima-Nishiwaki, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida

CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 ha d little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secr etion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation.
View on the web

Facilitators and barriers to engagement with contact tracing during infectious disease outbreaks: A rapid review of the evidence

als.fakia shared this article with you from Inoreader

journal.pone.0241473.g003&size=inline

by Odette Megnin-Viggars, Patrice Carter, G. J. Melendez-Torres, Dale Weston, G. James Rubin

Background

Until a vaccine is developed, a test, trace and isolate strategy is the most effective method of controlling the COVID-19 outbreak. Contact tracing and case isolation are common methods for controlling infectious disease outbreaks. However, the effectiveness of any contact tracing system rests on public engagement. Numerous factors may influence an individual's willingness to engage with a contact tracing system. Understanding these factors has become urgent during the COVID-19 pandemic.

Objective

To identify facilitators and barriers to uptake of, and engagement with, contact tracing during infectious disease outbreaks.

Method

A rapid systematic review was conducted to identify papers based on primary research, written in English, and that assessed facilitators, barriers, and other factors associated with the uptake of, and engagement with, a contact tracing system.

Principal findings

Four themes were identified as facilitators to the uptake of, and engagement with, contact tracing: collective responsibility; personal benefit; co-production of contact tracing systems; and the perception of the system as efficient, rigorous and reliable. Five themes were identified as barriers to the uptake of, and engagement with, contact tracing: privacy concerns; mistrust and/or apprehension; unmet need for more information and support; fear of stigmatization; and mode-specific challenges.

Conclusions

By focusing on the factors that have been identified, contact tracing services are more likely to get people to engage with them, identify more potentially ill contacts, and reduce transmission.

View on the web

Six-minute stepper test in hospitalized elderly patients: Convergent validity, test-retest reliability and safety

als.fakia shared this article with you from Inoreader

journal.pone.0241372.g007&size=inline

by Davi de Souza Francisco, Larissa Martinez, Aline Carleto Terrazas, Diego Britto Ribeiro, Wellington Pereira Yamaguti

Objective

To evaluate the convergent validity of the six-minute stepper test (6MST) with the variables used in the diagnosis of sarcopenia (appendicular muscle mass, handgrip strength and six-meter gait speed test), as well as to evaluate test-retest reliability and safety when applied to hospitalized elderly patients. Finally, we aimed to compare the performance in the 6MST between hospitalized elderly patients and healthy elderly from the community.

Materials and methods

Observational and cross-sectional study. Elderly patients admitted to a private hospital and healthy elderly from the community were recruited. On the first day, the patients included underwent the following assessments: anthropometric, handgrip strength (HGS), six-meter gait speed test (6GST) and 6MST. On the second day, before breakfast, patients underwent body composition assessment. The healthy elderly were evaluated on a single day and performed only anthropometric assessment and 6MST.

Results

30 hospitalized patients (age 71.0±7.9 years) and 15 healthy elderly (age 68.1±5.8 years) were included. There was a high correlation of 6MST with 6GST (r = 0.78; p Conclusion

6MST showed convergent validity with the functional variables used in the diagnosis of sarcopenia. In addition, excellent test-retest reliability was observed, which indicates the need for a single assessment in hospitalized elderly patients. The prevalence of adverse events during the application of the test is low, without resulting in clinical symptoms; therefore, the test is considered safe for this population. In addition, hospitalized elderly patients perform worse in the 6MST compared to healthy elderly from the community.

View on the web

Virtual reality as a tool for balance research: Eyes open body sway is reproduced in photo-realistic, but not in abstract virtual scenes

als.fakia shared this article with you from Inoreader

journal.pone.0241479.g004&size=inline

by Lorenz Assländer, Stephan Streuber

Virtual reality (VR) technology is commonly used in balance research due to its ability to simulate real world experiences under controlled experimental conditions. However, several studies reported considerable differences in balance behavior in real world environments as compared to virtual environments presented in a head mounted display. Most of these studies were conducted more than a decade ago, at a time when VR was still struggling with major technical limitations (delays, limited field-of-view, etc.). In the meantime, VR technology has progressed considerably, enhancing its capacity to induce the feeling of presence and behavioural realism. In this study, we addressed two questions: Has VR technology now reached a point where balance is similar in real and virtual environments? And does the integration of visual cues for balance depend on the subjective experience of presence? We used a state-of-the-art head mounted VR system and a custom-made balance platform to compare bal ance when viewing (1) a real-world environment, (2) a photo-realistic virtual copy of the real-world environment, (3) an abstract virtual environment consisting of only spheres and bars ('low presence' VR condition), and, as reference, (4) a condition with eyes closed. Body sway of ten participants was measured in three different support surface conditions: (A) quiet stance, (B) stance on a sway referenced surface, and (C) surface tilting following a pseudo-random sequence. A 2-level repeated measures ANOVA and PostHoc analyses revealed no significant differences in body sway between viewing the real world environment and the photo-realistic virtual copy. In contrast, body sway was increased in the 'low presence' abstract scene and further increased with eyes closed. Results were consistent across platform conditions. Our results support the hypothesis that state of the art VR reached a point of behavioural realism in which balance in photo-realistic VR is similar to balance in a real environment. Presence was lower in the abstract virtual condition as compared to the photo-realistic condition as measured by the IPQ presence questionnaire. Thus, our results indicate that spatial presence may be a moderating factor, but further research is required to confirm this notion. We conceive that virtual reality is a valid tool for balance research, but that the properties of the virtual environment affects results.
View on the web

Κυριακή 1 Νοεμβρίου 2020

Tongue muscle strength affects posterior pharyngeal wall advancement during swallowing: a cross‐sectional study of outpatients with dysphagia

gnorimies2015 shared this article with you from Inoreader

Abstract

Background

Tongue muscle strength is important for swallowing but decreases with age, in association with reduced skeletal muscle mass. However, the relationships between pharyngeal dynamics and both skeletal muscle mass and tongue muscle strength are unknown.

Objective

To investigate the effect of reductions in tongue muscle strength on pharyngeal movement during swallowing in patients with dysphagia.

Methods

Subjects were selected from male outpatients ≥65 years old who were examined for the main complaint of dysphagia. Patients with history of neurodegenerative disease affecting tongue movement, cerebrovascular disease, or oral cancer, were excluded. As a result, 82 men (mean age, 80.6±6.8 years) participated. Skeletal muscle mass index (SMI) as physical parameters and maximum tongue pressure (MTP) as tongue muscles strength were measured. Status and dynamics of the pharyngeal organs, including change in posterior pharyngeal wall advancement (PPWA) when swallowing 3.0 ml of moderately thick liquid, were measured by analyzing videofluoroscopic images. Simple bivariate correlation and multiple regression analysis were used to statistically analyze correlations between parameters.

Results

MTP showed a significant positive correlation with SMI (r = 0.43, p < 0.01). PPWA showed a significant negative correlation with MTP (r = ‐0.30, p < 0.01), but no association with SMI.

Conclusions

While tongue muscle strength is affected by skeletal muscle mass, posterior pharyngeal wall advancement is not readily affected by decreases in skeletal muscle mass. Posterior pharyngeal wall advancement may increase to compensate for swallowing function among individuals with reduced tongue muscle strength.

View on the web

Comparison of percutaneous dilatational tracheotomy versus open surgical technique in severe COVID-19: complication rates, relative risks and benefits

gnorimies2015 shared this article with you from Inoreader

1-s2.0-S0385814620X0006X-cov150h.gif

Publication date: Available online 28 October 2020

Source: Auris Nasus Larynx

Author(s): Cecilia Botti, Francesca Lusetti, Tommaso Neri, Stefano Peroni, Andrea Castellucci, Pierpaolo Salsi, Angelo Ghidini

View on the web

Drug concentration estimation using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancers

gnorimies2015 shared this article with you from Inoreader
In cases of head and neck cancer treated with intra-arterial chemotherapy, no objective indices are available for determining the distribution of anticancer drugs administered to multiple arteries. To establish such indices, noninvasive measurements of drug concentrations are required in the arterial perfusion area of each artery. In MRI, changes in 1/T1 (Δ1/T1) are correlated with the contrast agent concentration. We focused on these properties and investigated whether it is possible to estimate anticancer drug concentrations within tissue based on Δ1/T1.
View on the web

Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi‐institutional study

gnorimies2015 shared this article with you from Inoreader

Abstract

Background

The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility.

Methods

Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions.

Results

AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease‐specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS).

Conclusions

The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator.

View on the web

Family History of Cancer Predicts Allergic Rhinitis and Asthma Development

gnorimies2015 shared this article with you from Inoreader
The respiratory tract is a common entry point into the human body for both allergens and natural/manmade carcinogens, the latter of which could result in lung, gastrointestinal, and other malignancies.(1) We previously determined, in analyzing data from the National Health Interview Survey (NHIS) that there was a significant negative relationship between diagnoses of cancer with allergic rhinitis or asthma. The obstruction associated with both allergic rhinitis and asthma may act to block the entry of both allergens and carcinogens.(2) Although other studies have examined the relationship between personal cancer diagnoses in asthmatic or allergic individuals, or via biomarkers such as IgE, (3, 4), the heritability of such an effect, which may provide a survival benefit, has not been evaluated through family studies.
View on the web

Stimulierende und inhibierende Signalwege der APZ- und T-Zell-Interaktion sowie Einfluss von TLR-Agonisten auf APZ

gnorimies2015 shared this article with you from Inoreader
Via HNO

106.jpg

Zusammenfassung

Hintergrund

CD8+-T-Effektor-Zellen spielen eine Schlüsselrolle in der Identifikation und Elimination von Tumorzellen. Tumoren entkommen einer effektiven T‑Zell-Antwort durch Induktion eines Erschöpfungszustands, der die zytotoxische Kapazität der Effektorzellen mindert. Neuartige Checkpointinhibitoren wirken u. a. durch Reaktivierung erschöpfter, dysfunktionaler T‑Zellen. CD8+-T-Zellen eliminieren Tumorzellen nach Darbietung tumorspezifischer Antigene durch antigenpräsentierende Zellen (APZ). Die APZ-vermittelte Tumorerkennung wird v. a. Toll-like-Rezeptoren (TLR) stimuliert.

Ziel der Arbeit

Untersucht wurde der Einfluss von TLR-Agonisten auf APZ sowie stimulierende und inhibierende Signalwege der T‑Zell- und APZ-Interaktion.

Material und Methoden

Die Genexpression von Interleukin (IL-)12 und PDL1 wurde nach Stimulation von CD14+-Zellen mit CpG über 0, 8, 24 und 48 h analysiert. Die Expression des inhibitorischen kappa-B-Proteins (IκBα) nach Stimulation mit CpG wurde mittels Westernblot ausgewertet. CD8+-T-Zellen wurden über 72 h mit und ohne PD1-Checkpointblockade stimuliert und mittels Durchflusszytometrie auf die Expression von PD1, Tim‑3, CTLA4 und Lag3 untersucht.

Ergebnisse

Durch TLR-Stimulation (unmethylierte CpG-DNA) von APZ wurden immunstimulierende Signale wie die IL-12-Expression gesteigert, aber auch immuninhibierende Signalwege wie die PDL1-Expression aktiviert. Diese Signalwege werden NF-κB-vermittelt. Nach alleiniger Blockade der PD1-PDL1-Signalwege zeigte sich eine Überexpression anderer Immuncheckpointrezeptoren als potenzielle Ursache für fehlendes Ansprechen auf TLR-Stimulation mit PD1-Checkpointblockade.

Schlussfolgerung

Durch eine TLR-Stimulation exprimieren APZ im Tumormikromilieu NF-κB-vermittelt PDL1 und tragen so zur Erschöpfung von CD8+-T-Zellen bei. Der Effekt einer PD1-Blockade wird dabei potenziell durch Überexpression anderer Checkpointinhibitoren beeinträchtigt.

View on the web

Αναζήτηση αυτού του ιστολογίου