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Δευτέρα 2 Νοεμβρίου 2020

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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Evaluation of the relationship between non-caries cervical lesions and the tooth and periodontal tissue: An ex-vivo study using micro-computed tomography

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journal.pone.0240979.g001&size=inline

by Go-Eun Lim, Sung-Ae Son, Bock Hur, Jeong-Kil Park

The purpose of this study was to analyze the relationship between the height and depth of buccal non-carious cervical lesions (NCCLs) and the relationship between the size of buccal NCCLs and clinical crown-root ratio of both buccal and lingual (palatal) sides using micro-computed tomography (micro-CT) images of the teeth and periodontal tissues from the cadavers. The micro-CT images of 56 teeth and their supporting tissues were obtained from 17 cadavers. From these images, the height and depth of NCCLs and the length of the buccal and lingual (palatal) clinical crowns were measured, and the conventional/modified clinical crown-root ratios were calculated. The height and depth ratio of NCCLs were analyzed statistically with the conventional/modified crown-root ratios by Pearson's correlation and multiple regression. According to the Pearson's correlation, the height and depth of buccal NCCLs were positively correlated with the modified buccal clinical crown-root ratio (p p = 0.013, respectively). The regression model composed of variables of crown-root ratios explained the height of buccal NCCLs, and the prominent factor of the model was the modified buccal clinical crown-root ratio (p p = 0.004). The buccal NCCLs were related to the crown-root ratios; particularly, the level of buccal gingival margin could be associated with the formation of buccal NCCLs.
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Differences in location of cerebral white matter hyperintensities in children and adults living with a treated HIV infection: A retrospective cohort comparison

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journal.pone.0241438.g001&size=inline

by Jason G. van Genderen, Malon Van den Hof, Anders C. Boyd, Matthan W. A. Caan, Ferdinand W. N. M. Wit, Peter Reiss, Dasja Pajkrt

Cerebral white matter hyperintensities (WMH) persist in children and adults living with HIV, despite effective combination antiretroviral therapy (cART). As age and principal routes of transmission differ between children (perinatally) and adults (behaviorally), comparing the characteristics and determinants of WMH between these populations may increase our understanding of the pathophysiology of WMH. From separate cohorts of 31 children (NOVICE) and 74 adults (AGEhIV), we cross-sectionally assessed total WMH volume and number of WMH per location (periventricular vs. deep) using fluid-attenuated inversion recovery (FLAIR) MRI images. WMH were either periventricular when within 10mm of the lateral ventricles, or deep otherwise. We assessed patient- or HIV-related determinants of total WMH volume (adjusted for intracranial volume) and location of WMH using logistic regression, while stratifying on children and adults. At enrollment, median age of participants was 13.8 years (IQR 11.4–15.9) for children and 53.4 years (IQR 48.3–60.8) for adults and 27/31 children (87%) and 74/74 adults (100%) had an HIV RNA viral load p3 [425–2617] vs. 109 mm3 [61.7–625], p+ T-lymphocyte nadir with a higher number of periventricular WMH. Our findings suggest that the location of WMH differs between children and adults living with HIV, hinting at a different underlying pathogenesis.
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A minimally invasive catheterization of the external jugular vein in suckling piglets using ultrasound guidance

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journal.pone.0241444.g006&size=inline

by Hauteclaire Furbeyre, Etienne Labussiere

There is a growing interest for minimally invasive surgical procedures to improve experimental animal welfare. Minimally invasive catheterization procedures in pigs have been already developed using Seldinger technique but reproducibility is low, especially in young pigs. A novel method for a minimally invasive catheterization of external jugular vein was evaluated in suckling piglets of 21 days of age. Growth performance and haptoglobin concentration in plasma were measured throughout a four-week study in a group of seven catheterized piglets and a group of seven non-catheterized piglets. Catheterization was performed using Seldinger technique under continuous ultrasound monitoring for vein detection and needle insertion. The surgical procedure was quick and showed a great reproducibility. All catheters remained functional during the first week after catheterization. Catheterization in piglets did not significantly affect body weight (BW) and feed intake during four weeks after the surgical intervention compared to non-catheterized piglets (P > 0.10). Haptoglobin concentration in plasma was greater in catheterized piglets compared with non-catheterized piglets, with a significant increase over two weeks after catheter insertion (P
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Common childhood vaccines do not elicit a cross-reactive antibody response against SARS-CoV-2

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journal.pone.0241471.g002&size=inline

by Ahmed Kandeil, Mokhtar R. Gomaa, Ahmed El Taweel, Ahmed Mostafa, Mahmoud Shehata, Ahmed E. Kayed, Omnia Kutkat, Yassmin Moatasim, Sara H. Mahmoud, Mina Nabil Kamel, Noura M. Abo Shama, Mohamed El Sayes, Rabeh El-Shesheny, Mahmoud A. Yassien, Richard J. Webby, Ghazi Kayali, Mohamed A. Ali

Anecdotal evidence showed a negative correlation between Bacille Calmette-Guérin (BCG) vaccination and incidence of COVID-19. Incidence of the disease in children is much lower than in adults. It is hypothesized that BCG and other childhood vaccinations may provide some protection against SARS-CoV-2 infection through trained or adaptive immune responses. Here, we tested whether BCG, Pneumococcal, Rotavirus, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae, Hepatitis B, Meningococcal, Measles, Mumps, and Rubella vaccines provide cross-reactive neutralizing antibodies against SARS-CoV-2 in BALB/c mice. Results indicated that none of these vaccines provided antibodies capable of neutralizing SARS-CoV-2 up to seven weeks post vaccination. We conclude that if such vaccines have any role in COVID-19 immunity, this role is not antibody-mediated.
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An electrochemical biosensor for the detection of Mycobacterium tuberculosis DNA from sputum and urine samples

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journal.pone.0241067.g009&size=inline

by Daniel Ramos-Sono, Raúl Laureano, Daniel Rueda, Robert H. Gilman, Adolfo La Rosa, Jesús Ruiz, Raúl León, Patricia Sheen, Mirko Zimic

Tuberculosis (TB) is a major global public health problem with high mortality and morbidity. In low-middle income countries (LMIC) a large number of respiratory symptomatic cases that require TB screening per year demands more accurate, fast and affordable testing for TB diagnostics. Sputum smear is the initial screening test in LMICs, however, its sensitivity is limited in patients with low sputum bacilli load. The same limitation is observed in the currently available molecular tests. We designed, standardized and evaluated an electrochemical biosensor that detects the highly specific DNA insertion element 6110 (IS6110). A PCR amplified DNA product is hybridized on the surface of the working electrode built on FTO-Glass with immobilized specific DNA probes, after which cyclic voltammetry is performed with an Ag/AgCl reference electrode and a platinum counter electrode. The response of the sensor was measured by the ratio (cathodic peak current of the hybridized sensor) / (cathodic peak current of the non-hybridized sensor). We tested the biosensor, using positive hybridization control sequences, genomic DNA extracted from M. tuberculosis strains and sputum of TB patients, and extracted DNA from the urine of healthy controls spiked with M. tuberculosis DNA. This biosensor was effective for the detection of M. tuberculosis DNA with a detection limit of 16 fM in sputum sample and 1 fM in spiked urine samples. The low cost and the relatively brief duration of the assay make this an important TB screening tool in the fight against tuberculosis.
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The effects of PEGylation on LNP based mRNA delivery to the eye

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journal.pone.0241006.g006&size=inline

by Renee C. Ryals, Siddharth Patel, Chris Acosta, Madison McKinney, Mark E. Pennesi, Gaurav Sahay

Gene therapy is now an effective approach to treat many forms of retinal degeneration. Delivery agents that are cell-specific, allow for multiple dosing regimens, and have low immunogenicity are needed to expand the utility of gene therapy for the retina. We generated eight novel lipid nanoparticles (LNPs) ranging in size from 50 nm to 150 nm by changing the PEG content from 5% to 0.5%, respectively. Subretinal injections of LNP-mRNA encoding luciferase revealed that 0.5% PEG content within nanoparticles elicits the highest expression. Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. To investigate mechanisms of LNP delivery to the eye, we injected mCherry mRNA using the subretinal approach in apoE-/- and Mertk-/- mice. RPE transfection was observed in both mouse models suggesting that LNP intracellular delivery is not solely dependent on apolipoprotein adsorption or phagocytosis. To investigate LNP penetration, particles were delivered to the vitreous chamber via an intravitreal injection. The 0.5% PEG particles mediated the highest luciferase activity and expression was observed in the Müller glia, the optic nerve head and the trabecular meshwork, but failed to reach the RPE. Overall, particles containing less PEG (~150 nm in size) mediated the highest expression in the eye. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye.
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Neutrophil extracellular trap components and myocardial recovery in post-ischemic acute heart failure

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journal.pone.0241333.g003&size=inline

by Miriam Sjåstad Langseth, Geir Øystein Andersen, Trygve Husebye, Harald Arnesen, Manuela Zucknick, Svein Solheim, Jan Eritsland, Ingebjørg Seljeflot, Trine Baur Opstad, Ragnhild Helseth

Objective

The role of neutrophil extracellular traps (NETs) in acute heart failure is unknown. We recently showed that interleukin 8, a putative NETs stimulator, was associated with myocardial recovery in acute heart failure complicating ST-elevation myocardial infarction (STEMI). In this exploratory post-hoc study, we aimed to investigate the role of NETs components in relation to myocardial function and interleukin 8 in STEMI patients with symptomatic acute heart failure.

Methods

In 61 STEMI patients developing acute heart failure within 48 hours of successful revascularization, wall motion score index (WMSI), global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography at baseline and on day 5. Blood drawn at baseline and days 1, 2 and 5 was used to quantify double-stranded DNA (dsDNA), myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone 3 (CitH3). The area under the curve (AUC) of each NETs marker and int erleukin 8 was approximated for the first 5 days.

Results

dsDNAAUC and MPO-DNAAUC correlated significantly with change in WMSI from baseline to day 5 (rs = 0.28 for both, p≤0.05), whereas NETs AUCs did not correlate with changes in GLS and LVEF. dsDNAAUC was significantly correlated with interleukin 8AUC (r = 0.40, p = 0.003). However, mixed model regression could not identify a significant effect of the NETs components on myocardial function parameters.

Conclusions

In this cohort with acute heart failure complicating STEMI, NETs components were partly correlated with myocardial function and interleukin 8 levels, yet no causal relationship between NETs components and myocardial recovery could be established.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT00324766.

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Image-guided percutaneous sclerotherapy of venous malformations of the head and neck: Clinical and MR-based volumetric mid-term outcome

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journal.pone.0241347.g003&size=inline

by Dominik F. Vollherbst, Philipp Gebhart, Steffen Kargus, Astrid Burger, Reinald Kühle, Patrick Günther, Jürgen Hoffmann, Martin Bendszus, Markus A. Möhlenbruch

Objective

To report the clinical and MRI-based volumetric mid-term outcome after image guided percutaneous sclerotherapy (PS) of venous malformations (VM) of the head and neck.

Methods

A retrospective analysis of a prospectively maintained database was performed, including patients with VM of the head and neck who were treated with PS. Only patients with available pre- and post-interventional MRI were included into this study. Clinical outcome, which was subjectively assessed by the patients, their parents (for paediatric patients) and/or the physicians, was categorized as worse, unchanged, minor or major improvement. Radiological outcome, determined by MRI-based volumetric measurements, was categorized as worse (>10% increase), unchanged (≤10% increase to Results

Twenty-seven patients were treated in 51 treatment sessions. After a mean follow-up of 31 months, clinical outcome was worse for 7.4%, unchanged for 3.7% of the patients, while there was minor and maj or improvement for 7.4% and 81.5%, respectively. In the volumetric imaging analysis 7.4% of the VMs were worse and 14.8% were unchanged. Minor improvement was observed in 22.2%, intermediate improvement in 44.4% and major improvement in 11.1%. The rate of permanent complications was 3.7%.

Conclusion

PS can be an effective therapy to treat the symptoms of patients with VMs of the head and neck and to downsize the VMs. MRI-based volumetry can be used to objectively follow the change in size of the VMs after PS. Relief of symptoms frequently does not require substantial volume reduction.

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