Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 2 Νοεμβρίου 2020

Circulating blood extracellular vesicles as a tool to assess endothelial injury and chemotherapy toxicity in adjuvant cancer patients

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journal.pone.0240994.g006&size=inline

by Gil Bar-Sela, Idan Cohen, Adva Avisar, David Loven, Anat Aharon

Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs l abeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.
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Teenage pregnancy and experience of physical violence among women aged 15-19 years

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journal.pone.0241348.t004&size=inline

by John Tetteh, Benjamin D. Nuertey, Duah Dwomoh, Emilia Asuquo Udofia, Sheriff Mohammed, Evelyn Adjei-Mensah, Alfred Edwin Yawson

Background

Pregnant teenage women are prime targets of violence against women perpetrated by intimate partners, family members, and miscreants in their neighborhoods. This study estimated the prevalence of Teenage pregnancy (TP) and Physical Violence (PV) and further assessed the relationship between TP and PV in five Low-and-Middle-Income Countries (LMICs).

Methods

The study was conducted among five LIMCs (Burkina Faso, Kenya, Malawi, Nigeria, and Tanzania) using data from the most recent Demographic and Health Surveys conducted in these countries. Modified Poisson with the robust standard error was used to quantify the association between TP and PV. All analyses adjusted for the complex survey design structure (clustering, weighting, and stratification).

Results

The analysis involved a total of 26055 adolescent women aged 15–19 years across the five countries. The overall prevalence of TP was 25.4% (95%CI = 24.4–26.4) with the highest prevalence occurring among Malawians [29.0% (95%CI = 27.4–30.7)]. Meanwhile, the prevalence of TP among older adolescents (18–19 years) was approximately two-thirds significantly higher compared with young adolescents [aPR(95%CI) = 1.60[1.49–1.71)]. The prevalence of PV among teenagers across the five countries was 24.2% (95%CI = 22.3–26.2). The highest prevalence of PV was recorded among Nigerian adolescent women [31.8% (95%CI = 28.5–35.3)]. The prevalence of PV among adolescent women who were pregnant was approximately 5-folds significant compared to those who were not pregnant (adjusted prevalence ratio; aPR = 4.70; 95% CI: 3.86–5.73; p Conclusion

There was a high prevalence of pregnancy among older teenagers aged 18–19 years. Close to a quarter of teenage women ever experienced physical violence. Pregnant teenage women ever experience of physical violence was very high compared to non-pregnant peers. Intervention should target PV and TP by adopting a gender-sensitive approach to elim inate physical violence, particularly among teenagers to prevent TP.

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Differences in intrinsic aerobic capacity alters sensitivity to ischemia-reperfusion injury but not cardioprotective capacity by ischemic preconditioning in rats

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journal.pone.0240866.g005&size=inline

by Marie Vognstoft Hjortbak, Thomas Skjærlund Grønnebæk, Nichlas Riise Jespersen, Thomas Ravn Lassen, Jacob Marthinsen Seefeldt, Pernille Tilma Tonnesen, Rebekka Vibjerg Jensen, Lauren Gerard Koch, Steven L. Britton, Michael Pedersen, Niels Jessen, Hans Erik Bøtker

Introduction

Aerobic capacity is a strong predictor of cardiovascular mortality. Whether aerobic capacity influences myocardial ischemia and reperfusion (IR) injury is unknown.

Purpose

To investigate the impact of intrinsic differences in aerobic capacity and the cardioprotective potential on IR injury.

Methods

We studied hearts from rats developed by selective breeding for high (HCR) or low (LCR) capacity for treadmill running. The rats were randomized to: (1) control, (2) local ischemic preconditioning (IPC) or (3) remote ischemic preconditioning (RIC) followed by 30 minutes of ischemia and 120 minutes of reperfusion in an isolated perfused heart model. The primary endpoint was infarct size. Secondary endpoints included uptake of labelled glucose, content of selected mitochondrial proteins in skeletal and cardiac muscle, and activation of AMP-activated kinase (AMPK).

Results

At baseline, running distance was 203±7 m in LCR vs 1905±51 m in HCR rats (p0.99; HCR: 69±6%, p>0.99, respectively). Phosphorylaion of AMPK did not differ between LCR and HCR controls. IPC did not modulate cardiac phosphorylation of AMPK. Glucose uptake during reperfusion was similar in LCR and HCR rats. IPC increased glucose uptake during reperfusion in LCR animals (p = 0.02). Mitochondrial protein content in skeletal muscle was lower in LCR than in HCR (0.77±0.10 arbitrary units (AU) vs 1.09±0.07 AU, p = 0.02), but not in cardiac muscle.

Conclusion

Aerobic capacity is associated with altered myocardial sensitivity to IR injury, but the cardioprotective effect of IPC is not. Glucose uptake, AMPK activation immediately prior to ischemia and basal mitochondrial protein content in the heart seem to be of minor importance as underlying mechanisms for the cardioprotective effects.

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Hospital admission with non-alcoholic fatty liver disease is associated with increased all-cause mortality independent of cardiovascular risk factors

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journal.pone.0241357.g001&size=inline

by Jake P. Mann, Paul Carter, Matthew J. Armstrong, Hesham K. Abdelaziz, Hardeep Uppal, Billal Patel, Suresh Chandran, Ranjit More, Philip N. Newsome, Rahul Potluri

Non-alcoholic fatty liver disease (NAFLD) is common and strongly associated with the metabolic syndrome. Though NAFLD may progress to end-stage liver disease, the top cause of mortality in NAFLD is cardiovascular disease (CVD). Most of the data on liver-related mortality in NAFLD derives from specialist liver centres. It is not clear if the higher reported mortality rates in individuals with non-cirrhotic NAFLD are entirely accounted for by complications of atherosclerosis and diabetes. Therefore, we aimed to describe the CVD burden and mortality in NAFLD when adjusting for metabolic risk factors using a 'real world' cohort. We performed a retrospective study of patients followed-up after an admission to non-specialist hospitals with a NAFLD-spectrum diagnosis. Non-cirrhotic NAFLD and NAFLD-cirrhosis patients were defined by ICD-10 codes. Cases were age-/sex-matched with non-NAFLD hospitalised patients. All-cause mortality over 14-years follow-up after discharge was compared betw een groups using Cox proportional hazard models adjusted for demographics, CVD, and metabolic syndrome components. We identified 1,802 patients with NAFLD-diagnoses: 1,091 with non-cirrhotic NAFLD and 711 with NAFLD-cirrhosis, matched to 24,737 controls. There was an increasing burden of CVD with progression of NAFLD: for congestive heart failure 3.5% control, 4.2% non-cirrhotic NAFLD, 6.6% NAFLD-cirrhosis; and for atrial fibrillation 4.7% control, 5.9% non-cirrhotic NAFLD, 12.1% NAFLD-cirrhosis. Over 14-years follow-up, crude mortality rates were 14.7% control, 13.7% non-cirrhotic NAFLD, and 40.5% NAFLD-cirrhosis. However, after adjusting for demographics, non-cirrhotic NAFLD (HR 1.3 (95% CI 1.1–1.5)) as well as NAFLD-cirrhosis (HR 3.7 (95% CI 3.0–4.5)) patients had higher mortality compared to controls. These differences remained after adjusting for CVD and metabolic syndrome components: non-cirrhotic NAFLD (HR 1.2 (95% CI 1.0–1.4)) and NAFLD-cirrhosis (HR 3.4 (95% CI 2.8– 4.2)). In conclusion, from a large non-specialist registry of hospitalised patients, those with non-cirrhotic NAFLD had increased overall mortality compared to controls even after adjusting for CVD.
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The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

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journal.pone.0240942.g003&size=inline

by Li Liu, Ran Wang, Huihua Ding, Lei Tian, Ting Gao, Chunde Bao

Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positi ve correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69–0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response.
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Loss of p120ctn causes EGFR-targeted therapy resistance and failure

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journal.pone.0241299.g005&size=inline

by Mary E. Landmesser, Wesley M. Raup-Konsavage, Heather L. Lehman, Douglas B. Stairs

Epidermal growth factor receptor (EGFR) plays a vital role in cell division and survival signaling pathways. EGFR is activated in nearly every cancer type, and its high expression in tumors is correlated with poor patient outcome. Altogether, EGFR is a prime candidate as a therapeutic target. While targeted EGFR therapy is initially effective in 75% of patients, a majority of patients relapse within the first year due to poorly understood mechanisms of resistance. p120-catenin (p120ctn) has recently been implicated as a biomarker for EGFR therapy. In previous studies, we demonstrated that p120ctn is a tumor suppressor and its loss is capable of inducing cancer. Furthermore, p120ctn down-regulation synergizes with EGFR overexpression to cause a highly invasive cell phenotype. The purpose of this present study was to investigate whether p120ctn down-regulation induced EGFR therapeutic resistance. Using human esophageal keratinocytes, we have found that EGFR-targeting compounds are toxi c to cells overexpressing EGFR. Interestingly, these therapies do not cause toxicity in cells with EGFR overexpression and decreased p120ctn expression. These data suggest that decreased p120ctn causes resistance to EGFR therapy. We believe these findings are of utmost importance, as there is an unmet need to discover mechanisms of EGFR resistance.
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Risk factors for surgical site infections using a data-driven approach

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journal.pone.0240995.t005&size=inline

by J. M. van Niekerk, M. C. Vos, A. Stein, L. M. A. Braakman-Jansen, A. F. Voor in 't holt, J. E. W. C. van Gemert-Pijnen

Objective

The objective of this study was to identify risk factors for surgical site infection from digestive, thoracic and orthopaedic system surgeries using clinical and data-driven cut-off values. A second objective was to compare the identified risk factors in this study to risk factors identified in literature.

Summary background data

Retrospective data of 3 250 surgical procedures performed in large tertiary care hospital in The Netherlands during January 2013 to June 2014 were used.

Methods

Potential risk factors were identified using a literature scan and univariate analysis. A multivariate forward-step logistic regression model was used to identify risk factors. Standard medical cut-off values were compared with cut-offs determined from the data.

Results

For digestive, orthopaedic and thoracic system surgical procedures, the risk factors identified were preoperative temperature of ≥38°C and antibiotics used at the time of surgery. C-reactive protei n and the duration of the surgery were identified as a risk factors for digestive surgical procedures. Being an adult (age ≥18) was identified as a protective effect for thoracic surgical procedures. Data-driven cut-off values were identified for temperature, age and CRP which can explain the SSI outcome up to 19.5% better than generic cut-off values.

Conclusions

This study identified risk factors for digestive, orthopaedic and thoracic system surgical procedures and illustrated how data-driven cut-offs can add value in the process. Future studies should investigate if data-driven cut-offs can add value to explain the outcome being modelled and not solely rely on standard medical cut-off values to identify risk factors.

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Neural correlates of standing imagery and execution in Parkinsonian patients: The relevance to striatal dopamine dysfunction

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journal.pone.0240998.g004&size=inline

by Yutaro Mori, Etsuji Yoshikawa, Masami Futatsubashi, Yasuomi Ouchi

It has been reported that the cerebellar vermis is equally involved in both motor imagery about axial movement and the actual execution of postural balance in healthy human subjects, but this finding is yet to be explored in Parkinson's disease (PD). We therefore investigated the neuronal responses during observation of standing posture, imagination of standing and the assumption of an upright posture in ten drug-naïve PD patients using positron emission tomography (PET) with [15O]H2O and evaluated dopamine dysfunction by measuring the level of dopamine transporter binding of [11C]CFT. Within-group statistical parametric mapping (SPM) analysis showed similar cerebellar activation during imagination of standing and its real execution between the PD and control groups (12 healthy subjects); i.e., increases in regional cerebral blood flow (rCBF) were observed in the anterior cerebellar vermis during motor imagination and the posterior vermis during st anding. A comparison between the groups showed that the motor execution of standing significantly activated the superior part of the posterior vermis (declive VI) and the paracentral sulcus region in the PD patients, while the prefrontal cortices were deactivated during standing (p11C]CFT binding (p11C]CFT binding (p
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Changes in metamorphopsia after the treat-and-extend regimen of anti-VEGF therapy for macular edema associated with branch retinal vein occlusion

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journal.pone.0241343.g004&size=inline

by Kenichiro Mori, Keijiro Ishikawa, Iori Wada, Yuki Kubo, Yoshiyuki Kobayashi, Takahito Nakama, Masatoshi Haruta, Masato Akiyama, Shintaro Nakao, Shigeo Yoshida, Koh-Hei Sonoda

This study aims to investigate the changes in metamorphopsia after administering the treat-and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular endothelial growth factor agents using the treat-and-extend regimen for ≥18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best-corrected visual acuity (logarithm of minimum angle of resolution) and central macular thickness significantly improved at 18 months compared to baseline, the median value (interquartile range [IQR]), 0.30 (0.15–0.52) and 459 (373–542) μm at baseline, and 0 (-0.08–0.16) and 267 (232–306) μm at 18 months. The M-CHARTS score (the mean of vertical and horizontal sc ores) significantly decreased at 1, 6, and 12 months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250–0.925), 0.4 (0.15–0.70), 0.4 (0.150–0.625), 0.4 (0.225–0.550) and 0.45 (0.225–0.750) at baseline, 1 month, 6 months, 12 months and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR, 0.5–3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change in the mean M-CHARTS score at 18 months was significantly correlated with the baseline score and the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy using the treat-and-extend regimen improved metamorphopsia in branch retinal vein occlusion-related macular edema in the short to mid-term follow-up period, but not in the long term. Macular edema recurrence may be associated with persistent metamorphopsia.
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Serum IgG titers against periodontal pathogens are associated with cerebral hemorrhage growth and 3-month outcome

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journal.pone.0241205.t004&size=inline

by Masahiro Nakamori, Naohisa Hosomi, Hiromi Nishi, Shiro Aoki, Tomohisa Nezu, Yuji Shiga, Naoto Kinoshita, Kenichi Ishikawa, Eiji Imamura, Tomoaki Shintani, Hiroki Ohge, Hiroyuki Kawaguchi, Hidemi Kurihara, Shinichi Wakabayashi, Hirofumi Maruyama

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multiva riate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52–18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08–57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.
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Comparing static and dynamic emotion recognition tests: Performance of healthy participants

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journal.pone.0241297.g001&size=inline

by Sara Khosdelazad, Lieke S. Jorna, Skye McDonald, Sandra E. Rakers, Rients B. Huitema, Anne M. Buunk, Jacoba M. Spikman

Facial expressions have a communicatory function and the ability to read them is a prerequisite for understanding feelings and thoughts of other individuals. Impairments in recognition of facial emotional expressions are frequently found in patients with neurological conditions (e.g. stroke, traumatic brain injury, frontotemporal dementia). Hence, a standard neuropsychological assessment should include measurement of emotion recognition. However, there is debate regarding which tests are most suitable. The current study evaluates and compares three different emotion recognition tests. 84 healthy participants were included and assessed with three tests, in varying order: a. Ekman 60 Faces Test (FEEST) b. Emotion Recognition Task (ERT) c. Emotion Evaluation Test (EET). The tests differ in type of stimuli from static photographs (FEEST) to more dynamic stimuli in the form of morphed photographs (ERT) to videos (EET). Comparing performances on the three tests, the lowest total scores (67 .3% correct answers) were found for the ERT. Significant, but moderate correlations were found between the total scores of the three tests, but nearly all correlations between the same emotions across different tests were not significant. Furthermore, we found cross-over effects of the FEEST and EET to the ERT; participants attained higher total scores on the ERT when another emotion recognition test had been administered beforehand. Moreover, the ERT proved to be sensitive to the effects of age and education. The present findings indicate that despite some overlap, each emotion recognition test measures a unique part of the construct. The ERT seemed to be the most difficult test: performances were lowest and influenced by differences in age and education and it was the only test that showed a learning effect after practice with other tests. This highlights the importance of appropriate norms.
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