Search

Living organisms are now constantly exposed to microplastics and nanoplastics (MNPLs), and besides their toxic potential, they can also act as carriers of various hazardous elements such as heavy metals. Therefore, this study explored possible interactions between polystyrene microplastics (PSMPLs) and two metal pollutants: cadmium chloride (CdCl 2 ) and silver nitrate (AgNO 3 ). To better understand the extent of biological effects caused by different sizes of PSMPLs, we conducted in vivo experiments with five doses (from 0.01 to 10 mM) that contained polystyrene particles measuring 4, 10, and 20 µm in size on Drosophila larvae. Additional experiments were performed by exposing larvae to two individual metals, CdCl 2 (0.5 mM) and AgNO 3 (0.5 mM), as well as combined exposure to PSMPLs (0.01 and 10 mM) and these metals, in an attempt to gain new insight into health risks of such co-exposure. Using transmission electron microscopy imaging, we managed to visualize the biodistribution of ingested PSMPLs throughout the fly's body, observing the interactions of such plastics with Drosophila intestinal lumen, cellular uptake by gut enterocytes, the passage of plastic particles through the intestinal barrier to leak into the hemolymph, and cellular uptake by hemocytes. Observations detected size and shape changes in the ingested PSMPLs. Egg-to-adult viability screening revealed no significant toxicity upon exposure to individual doses of tested materials; however, the combined exposure to plastic and metal particles induced aggravated genotoxic effects, including intestinal damage, genetic damage, and intracellular oxidative stress (ROS generation), with smaller sized plastic particles + metals (cadmium and silver) causing greater damage.

Background: In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II., Methods/design: APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments., Discussion: APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Clinical studies have demonstrated that IL-17A inhibition with secukinumab is effective for clearing the skin of patients with psoriasis and has a favorable safety profile., Objective: The authors aim to determine whether secukinumab is effective and safe for the treatment of moderate-to-severe chronic psoriasis based on clinical experience with this drug., Method: The authors conducted a multicenter retrospective study in nine referral centers and included patients with psoriasis who had received secukinumab between March 2018 to November 2020. Data on demographic characteristics, Psoriasis Area and Severity Index (PASI) scores, and previous treatments were collected from medical records. Patients were evaluated at 12, 24, and 52 weeks with respect to response to treatment and side effects., Results: In total, 229 patients were recruited for the study. A PASI score improvement of ≥90 points over the baseline was achieved by 79%, 69.8%, and 49.3% of patients at weeks 12, 24, and 52, respectively. The most common adverse events wereCandida infections and fatigue. In total, 74 (32%) patients discontinued treatment by week 52, including due to adverse events, or secondary ineffectiveness., Study Limitations: Retrospective design., Conclusions: These findings suggest that secukinumab therapy is reasonably effective in patients with moderate-to-severe psoriasis. Comorbidities and time length of the disease can affect the response to treatment. The rates of adverse events were high in this patient population., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Objective: Parkinson's disease (PD) is a common neurological disorder with variable clinical manifestations and magnetic resonance imaging (MRI) findings. We propose a handcrafted image classification model that can accurately (i) classify different PD stages, (ii) detect comorbid dementia, and (iii) discriminate PD-related motor symptoms., Methods: Selected image datasets from three PD studies were used to develop the classification model. Our proposed novel automated system was developed in four phases: (i) texture features are extracted from the non-fixed size patches. In the feature extraction phase, a pyramid histogram-oriented gradient (PHOG) image descriptor is used. (ii) In the feature selection phase, four feature selectors: neighborhood component analysis (NCA), Chi2, minimum redundancy maximum relevancy (mRMR), and ReliefF are used to generate four feature vectors. (iii) Two classifiers: k-nearest neighbor (kNN) and support vector machine (SVM) are used in the classification step. A ten-fold cross-validation technique is used to validate the results. (iv) Eight predicted vectors are generated using four selected feature vectors and two classifiers. Finally, iterative majority voting (IMV) is used to attain general classification results. Therefore, this model is named nested patch-PHOG-multiple feature selectors and multiple classifiers-IMV (NP-PHOG-MFSMCIMV)., Results: Our presented NP-PHOG-MFSMCIMV model achieved 99.22, 98.70, and 99.53% accuracies for the collected PD stages, PD dementia, and PD symptoms classification datasets, respectively., Significance: The obtained accuracies (over 98% for all states) demonstrated the performance of developed NP-PHOG-MFSMCIMV model in automated PD state classification., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

New insights into the interactions between nanopesticides and edible plants are required in order to elucidate their impacts on human health and agriculture. Nanopesticides include formulations consisting of organic/inorganic nanoparticles. Drosophila melanogaster has become a powerful model in genetic research thanks to its genetic similarity to mammals. This project mainly aimed to generate new evidence for the toxic/genotoxic properties of different nanopesticides (a nanoemulsion (permethrin nanopesticides, 20 ± 5 nm), an inorganic nanoparticle as an active ingredient (copper(II) hydroxide [Cu(OH) 2 ] nanopesticides, 15 ± 6 nm), a polymer-based nanopesticide (acephate nanopesticides, 55 ± 25 nm), and an inorganic nanoparticle associated with an organic active ingredient (validamycin nanopesticides, 1177 ± 220 nm)) and their microparticulate forms (i.e., permethrin, copper(II) sulfate pentahydrate (CuSO 4 ·5H 2 O), acephate, and validamycin) widely used against agricultural pests, while also showing the merits of using Drosophila -a non-target in vivo eukaryotic model organism-in nanogenotoxicology studies. Significant biological effects were noted at the highest doses of permethrin (0.06 and 0.1 mM), permethrin nanopesticides (1 and 2.5 mM), CuSO 4 ·5H 2 O (1 and 5 mM), acephate and acephate nanopesticides (1 and 5 mM, respectively), and validamycin and validamycin nanopesticides (1 and 2.5 mM, respectively). The results demonstrating the toxic/genotoxic potential of these nanopesticides through their impact on cellular internalization and gene expression represent significant contributions to future nanogenotoxicology studies.

The podocyte is a key cell in maintaining renal filtration barrier integrity. Several recent studies have analyzed the genome and transcriptome in the podocyte at deep resolution. This avenue of "podocyte-ome" research was enabled by a variety of techniques, including 1 ) single-cell transcriptomics, 2 ) FACS with and without genetically encoded markers, and 3 ) deep proteomics. However, data across various omics techniques and studies are currently not well integrated with each other. Here, we aimed to establish a common, simplified knowledge base for the mouse podocyte-ome by integrating bulk RNA sequencing, bulk proteomics of FACS-sorted podocytes, and single-cell transcriptomics. Three publicly available datasets of each omics technique from different laboratories were bioinformatically integrated and visualized. Our approach not only revealed conserved processes of podocytes but also sheds light on the benefits and limitations of the used technologies. We identified that high expression of glycan glycosylphosphatidylinositol anchor synthesis and turnover, as well as retinol metabolism, were relatively understudied features of podocytes. In addition, actin-binding molecules were organized in a podocyte-specific manner, as evidenced by differential expression in podocytes compared with other glomerular cells. We compiled a Web-based "PodIent" application that illustrates the features of the integrated dataset. This enables user-driven exploratory analysis by querying genes of interest for podocyte identity in absolute and relative quantification while also linking to functional annotation using keywords, Gene Ontology terms, and gene set enrichments. This consensus draft is a first step toward common molecular omics knowledge of kidney cells. NEW & NOTEWORTHY Podocytes are key components of glomerular filtration and are affected in various kidney diseases. Here, we present an integrated, robust definition of molecular identity across proteomic, single-cell transcriptomics, and bulk transcriptomic studies on native mouse podocytes. We created the "PodIdent" app, a novel knowledge base promoting access to the presence and expression of specific proteins for podocytes.

Objectives: This study aims to present our experience on anakinra, a recombinant interleukin-1 (IL-1) receptor antagonist, and efficacy results in pediatric rheumatic diseases in our clinic., Patients and Methods: Between July 1 st , 2016 and July 1 st , 2020, a total of 33 pediatric patients (18 males, 15 females; mean age: 6±3.4 years; range 4 to 13 years) with pediatric rheumatic diseases who were treated with anakinra were retrospectively analyzed. The patients with over one-month treatment period and followed for at least one year were included. Demographic and clinical findings, outcomes, adverse events, prior and/or additional treatments were collected at baseline, at 3 and 12 months of therapy., Results: There were 33 patients with different pediatric rheumatic diseases (11 with systemic juvenile idiopathic arthritis [sJIA] complicated by macrophage activation syndrome [MAS], six with hyperimmunoglobulin-D syndrome, five with cryopyrin-associated periodic syndrome, five with familial Mediterranean fever, four with idiopathic recurrent pericarditis, one with NLRP12-associated periodic fever syndrome and one with unclassified systemic autoinflammatory disease), in the study group. The complete response was observed 69.7% of patients, partial response in 24.2%, and no response in 6.1% at three months of treatment. Inactive disease status was achieved in 45.5% of the patients with remission-on medication and 18.2% of the patients with remission-off medication at the end of a year. Anakinra was switched to other biological treatments in 51.5% of patients (n=17). Biological switch to canakinumab and tocilizumab were observed in 70.6% and 29.4% of these patients. Except for local reactions (n=2), no adverse events were observed in any of the patients., Conclusion: Anakinra appears to be a promising treatment alternative owing to its rapid effect as a result of its short half-life in autoinflammatory conditions. While short-term therapy seems to be sufficient for the sJIA complicated by MAS, the patients with systemic autoinflammatory diseases maintenance a more anakinra-dependent course., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish League Against Rheumatism.)

Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13 C 6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease., (© 2022. The Author(s).)

Problem: Although pregnant women with gestational diabetes (GD), morbidly adherent placenta (MAP), and pregnancy hypertension (pHT) diseases lead to intrauterine growth restriction (IUGR), little is known about their effect on mucosal-associated invariant T (MAIT) and innate lymphoid cells (ILC) in the umbilical cord. This study aimed to quantify and characterize MAIT cells and ILCs in the cord blood of pregnant women with GD, MAP, and pHT diseases., Method of Study: Cord blood mononuclear cells (CBMCs) were isolated by Ficoll-Paque gradient. CD3 + TCRVα7.2 + CD161 high cells and ILC subsets were quantified by flow cytometry. CBMCs were stimulated with PMA/Ionomycin and Golgi Plug for 4 h and stained for IFN-γ, TNF-α, and granzyme B. The stained cells were analyzed on FACS ARIA III., Results: Compared with healthy pregnancies, in the cord blood of the pHT group, elevated number of lymphocytes was observed. Moreover, the absolute number of IFN-γ producing CD4 + or CD4 - subsets of CD3 + TCRVα7.2 + CD161 high cells as well as those producing granzyme B were significantly elevated in the pHT group compared to healthy controls suggesting increased MAIT cell activity in the pHT cord blood. Similarly, in the MAP group, the absolute number of total CD3 + TCRVα7.2 + CD161 high cells, but not individual CD4 + or negative subsets, were significantly increased compared with healthy controls' cord blood. Absolute numbers of total CD3 + TCRVα7.2 + CD161 high cells and their subsets were comparable in the cord blood of the GD group compared with healthy controls. Finally, the absolute number of total ILCs and ILC3 subset were significantly elevated in only pHT cord blood compared with healthy controls. Our data also reveal that IFN-γ + or granzyme B + cell numbers negatively correlated with fetal birth weight., Conclusions: CD3 + TCRVα7.2 + CD161 high cells and ILCs show unique expansion and activity in the cord blood of pregnant women with distinct diseases causing IUGR and may play roles in fetal growth restriction., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Isolated restrictive foramen ovale (rFO) without complex heart defects is a rare pathology. There may be difficulties in managing this situation, which can lead to right heart enlargement, tricuspid regurgitation and hydrops findings in the foetus. We conducted a retrospective analysis of 8451 foetuses. 7883 (93.2%) had a structurally normal heart or minor heart disease, 18 (0.22%) of which had a diagnosis of isolated rFO. Nine patients with neonatal echocardiographic examination were included in the study. In 8 (88.8%) patients, it was stated that a decision to give birth should be made at the time of presentation. Evaluating postpartum echocardiographic examinations, 7 (77.7%) patients had normal or minor defects. The decision of delivery made at the right time during follow-up is critical to determine the prognosis.IMPACT STATEMENT What is already known on this subject? The data about the prenatal diagnosis of isolated rFO is limited. What the results of this study add? We conducted a retrospective analysis of 8451 foetuses. 7883 (93.2%) foetuses had a structurally normal heart or minor heart disease, 18 (0.22%) of which had a diagnosis of rFO. Nıne patients with foetal and postnatal follow-up and echocardiographic findings were examined in the study. The group's median gestational age at admission was 35.0 weeks (range: 27.0-39.0 weeks). The delivery decision was made in 8 (88.8%) patients at the time of admission. Evaluating postpartum echocardiographic examinations, 7 (77.7%) patients had normal or minor defects. Additionally, one patient was diagnosed with cardiomyopathy, and the other patient was diagnosed with functional pulmonary atresia. No death occurred in any foetus during follow-up. What the implications are of these findings for clinical practice and/or further research? Isolated rFO, a rare condition in the foetus, is generally well-tolerated in foetal life. However, the right heart enlargement, tricuspid regurgitation, or hydrops findings can be seen in patients. The decision of delivery made at the right time during follow-up is critical to determine the prognosis.

To evaluate the vaccine response of treatment-naive juvenile idiopathic arthritis (JIA) patients who were fully vaccinated against Hepatitis B Virus (HBV) and then compare their antibody status with healthy controls. In this multicenter study, initial visit hepatitis B surface antigen (HbsAg) and anti-hepatitis B surface antibody (anti-Hbs) titers of 262 treatment-naive JIA patients who were followed up regularly between May 2015 and October 2019 were evaluated retrospectively from patients' medical records and compared with 276 healthy peers. Both HbsAg and anti-Hbs antibody titers were tested by the ELISA technique. Anti-HBs titers ≥ 10 IU/L were considered as reactive indicating seroprotection against HBV. In the JIA group, seropositivity rate was 59.1% while 72.9% of the control group were immune against HBV (p = 0.002). The median titer for anti-Hbs was 14 (range: 0-1000) IU/L in the patient group and 43.3 (range: 0-1000) IU/L in the control group (p = 0.01). Neither JIA patients nor healthy controls were positive for HbsAg. Patients with JIA vaccinated according to the national vaccination schedule were evaluated at their first visit in pediatric rheumatology outpatient clinics for anti-Hbs presence and it was found that they have lesser seroprotectivity than their age and sex-matched routinely vaccinated, healthy peers. So, to complete missing vaccines and booster vaccine doses, assessing the immune status of the patients at the time of diagnosis against HBV should be in the check-list of physicians dealing with pediatric rheumatic diseases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: The multiple endoclip retraction technique (MERT) was developed based on our experience with suturing renal parenchyma in laparoscopic partial nephrectomy. In this study we prospectively evaluated the one-year results of cases treated by transperitoneal laparoscopic Burch with the MERT., Methods: The patients were evaluated with stress test, one-hour pad test, and were requested to complete the International Continence Society Incontinence Questionnaire short form (ICIQ-SF) in the postoperative period. The follow-up periods were postoperative 3, 6, and 12 months., Results: The primary outcome of this study was surgical success, defined as being cured of stress urinary incontinence (SUI) (no symptoms), experiencing improved symptoms of SUI in ICIQ-SF and negative stress test, and less than 2g urine leakage in a one-hour pad test.No statistically significant difference was found in terms of age, number of children, and body mass index (BMI) in patients according to the results of the 12 month postoperative stress test. We found statistically significant improvements at all control months in terms of stress test and pad weight. ICIQ-SF results showed a significant decrease at three months in patients who recovered after the operation. This rate has not changed in following control months. However, there was no statistical change in ICIQ-SF values in patients who did not recover after the operation., Conclusion: MERT seems to be one of the safe and effective modifications in the management of SUI with good one year outcomes when performed by suitably trained experienced surgeons., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Lipoblastoma is a rare benign tumor originating from adipose tissue, usually seen in infancy and early childhood. Here, we present a case of scalp lipoblastoma in a 4-month-old that we treated surgically and review the literature. Although lipoblastomas may be seen in various locations during infancy and early childhood, rarely, they can also develop in the scalp., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mask use can lead to facial dermatoses due to factors, such as hyperhydration, seborrhea, high humidity caused by sweating, and the occlusive effect of the mask., Aim: We investigated mask-related facial dermatoses in healthcare personnel who, since the beginning of the COVID-19 pandemic, had to wear a mask for long hours., Methods: In this study, healthcare professionals working at Medipol Mega University Hospital since the beginning of the pandemic were screened for facial dermatoses between December 2020 and February 2021 with a dermatological examination and interview., Results: Of the 101 healthcare professionals, 51 (50.5%) were doctors and 50 (49.5%) nurses, and 36 (35.6%) were male and 65 (64.4%) were female. All the participants had been actively working at the hospital for 35-46 weeks since the beginning of the pandemic and wearing N95 or surgical masks for an average of 6-13 h a day. During the dermatological examination, the most common facial dermatosis was acne, which was observed in 55.4% (n = 56) of the cases. Of the 56 acne cases, 41.1% (n = 23) had acne in their history, while 58.9% (n = 33) had new-onset acne. Being female, using a N95 surgical mask compared to surgical mask, and the daily average duration of mask use were determined as risk factors for acne development due to mask use., Conclusions: The use of masks, more frequently N95, caused both an increase in existing acne and the development of new acne., (© 2021 Wiley Periodicals LLC.)

1,4-Dioxane (DXN) is used as solvent in different consumer products including cosmetics, paints, surfactants, and waxes. In addition, DXN is released as an unwanted contaminating by-product as a result of some reactions including ethoxylation of alcohols, which occurs with in personal care products. Consequently, DXN pollution was detected in drinking water and is considered as an environmental problem. At present, the genotoxicity effects attributed to DXN are controversial. The present study using an in vivo model organism Drosophila melanogaster aimed to determine the toxic/genotoxic, mutagenic/recombinogenic, oxidative damage as evidenced by ROS production, phenotypic alterations as well as behavioral and developmental alterations that are closely related to neuronal functions. Data demonstrated that nontoxic DXN concentration (0.1, 0.25, 0.5, or 1%) induced mutagenic (1%) and recombinogenic (0.1, 0.25, or 0.5%) effects in wing spot test and genotoxicity in hemocytes using comet assay. The nontoxic concentrations of DXN (0.1, 0.25, 0.5, or 1%) significantly increased oxidative stress, climbing behavior, thermal sensivity and abnormal phenotypic alterations. Our findings show that in contrast to in vitro exposure, DXN using an in vivo model Drosophila melanogaster this compound exerts toxic and genotoxic effects. Data suggest that additional studies using other in vivo models are thus warranted.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: In the evaluation of children with Kawasaki disease (KD), the age of onset is important and complications may occur if the distinctive features are not assessed accordingly. The objective of the study is to define the clinical and laboratory presentations and treatment outcomes of KD in infants ≤6 months of age compared to those >6 months multicentrically., Methods: This retrospective study reviewed the medical records of the patients diagnosed with KD and followed up between January 2009 and January 2019., Results: A total of 204 KD patients were enrolled and grouped according to age as Group I (≤6 months, n = 31) and Group II (>6 months, n = 173). Except for cervical adenopathy (19.3% vs. 47.4%, p = 0.03), the major clinical manifestations of KD were similar between groups I and II. However, the frequency of incomplete and atypical KD was higher in Group I (38.7% vs. 24.8%, p = 0.04, 38.7% vs. 8.1% p < 0.001, respectively). Clinical features such as vomiting/diarrhea (19.3% vs. 1.1% p < 0.001), aseptic meningitis (19.3% vs. 2.3%, p = 0.001) were more common in Group I. Percentage of neutrophils (45.5 vs. 36, p = 0.004) and hemoglobin levels (8 vs. 10.5 gr/dL, p = 0.02) were statistically lower and platelet count (737,000 vs 400,000/mm 3 , p = 0.004) was statistically higher in group I. Coronary artery lesions (CALs) were more common in Group I (48% vs. 20%, p < 0.001). Harada and Kobayashi scores appear to be effective in predicting coronary artery lesions (CALs) and IVIG resistance in the entire cohort. There was no diagnostic delay in group I (5.5 vs 6.5 days, p = 0.88)., Conclusions: Since clinical presentations and laboratory features of KD may vary with age, and the frequency of atypical and incomplete presentations is high, awareness of KD in young children should be raised among pediatricians.

As of Aug. 2, 2021, 1693 injury claims associated with COVID-19 medical countermeasures have been filed in the Countermeasures Injury Compensation Program (CICP), of which 686 claims were related to COVID-19 vaccines and urgently needed compensation decisions. However, from an economic and public policy perspective, we find that the CICP design has unintended consequences: locating CICP in the executive agency DHHS potentially creates a conflict of interest, and not permitting judicial review generates a lack of checks and balances, both of which could jeopardize justice. These fundamental problems would subsequently weaken four key performance indicators of CICP compared with its judicial counterpart in the Court of Federal Claims. CICP lacks accountability, transparency, and cost-effectiveness efficiency, with 94% of its total costs spent on administration rather than compensation. CICP's ability to compensate is also questionable. If COVID-19 claims were compensated at its historical rate, CICP would face around $21.16 million in compensation outlays and $317.94 million in total outlays, 72.1 times its current balance. To ensure just compensation for injured petitioners during COVID-19 and future public health emergencies, we recommend Congress (1) initiate a major reform by relocating CICP from DHHS to the Claims Court or (2) keep CICP within DHHS and make incremental changes by permitting judicial review of DHHS administrative adjudication of CICP claims. We further recommend Congress audit and adjust budgets for CICP and DHHS promptly propose an injury table for COVID-19 claims. This is the first study that contributes an economic perspective to the limited literature on CICP and also provides unique and rich economic data., (© The Author(s) 2022. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School.)

Introduction: It is well known that serum iron parameters are closely related to cardiovascular health. Iron deficiency may lead to significant cardiac problems, such as atrioventricular conduction abnormalities, and systolic and/or diastolic dysfunction. Studies related to the effect of iron deficiency on cardiac functions are limited in children. Therefore, the aim of this study was to evaluate the effect of low iron stores on cardiac repolarization parameters which are used to predict arrhythmia and cardiac functions., Materials and Methods: Onehundred thirty-five children 2 to 18 years of age without structural heart disease who were referred to the Pediatric Cardiology Department for various reasons such as chest pain, heart murmur, or evaluation before sports participation were evaluated prospectively. The cases were separated into 3 groups according to ferritin levels (group 1: ferritin <15 ng/mL [n=48], group 2: ferritin 15 to 25 ng/mL [n=51], and group 3: ferritin >25 ng/mL [n=36]). Evaluations were made with detailed 12-lead surface electrocardiography (ECG) and transthoracic echocardiogram. Cardiac repolarization parameters were measured from surface ECG and systolic functions, left ventricular wall diameters were evaluated from transthoracic echocardiogram., Results: Eighty-four (62.2%) girls and 51 (37.8%) boys are included in the study. The average age of the groups was similar. In children with low ferritin levels (group 1); Pw, Pw max, and Pw dis; QT, QTc, and QTc dis; Tp-Te, Tp-Te dis, Tp-Te/QT, and Tp-Te/QTc were significantly longer compared with the group 3 (P<0.05). There was a negative correlation between ferritin level and Pw, P max, and Pw dis; QT, QT dis, QTc, and QTc dis; Tp-Te, Tp-Te dis, Tp-Te/QT, and Tp-Te/QTc (P<0.05). No correlation was found between ferritin level and Pw min. There was no difference between the groups in respect of ejection phase indices, heart wall measurements, and end-diastolic diameter measurements., Conclusion: Iron deficiency may be related to the tendency of arrhythmias in children without structural heart disease. Therefore, careful evaluation of ECG parameters of healthy children with low iron stores, and follow up with intermittent monitoring is highly important., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course., Methods: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group., Results: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features ( n = 100); cluster II, predominantly MAS-like features ( n = 34); cluster III, predominantly LV dysfunction ( n = 47); cluster IV, other presentations ( n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil-lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts., Conclusion: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To review the real-life data, to provide an input to the literature concerning treatment of juvenile idiopathic arthritis (JIA) with adalimumab (ADL) biosimilar., Method: This multi-centric retrospective study was conducted among children with JIA, followed up for at least 24-weeks from the initiation of ADL biosimilar (ABP 501) treatment. Adverse events and alterations in disease activity scores were figured out., Results: The median age of the group was 15.5 (5-18) years. JIA categories were oligoarticular (n =12), enthesitis-related (ERA) (n=24), psoriatic (PsA) (n=6), and polyarticular (n=4). Uveitis was detected at the initiation of the disease (n=3), during the disease course (n=5), or before the diagnosis (n=1). The first-line treatment preferences were ADL biosimilar (n=37) and etanercept (n=9). On the 6th month of ABP 501, 40 (86.9%) patients had achieved complete remission. Six patients (1 PsA, 1 polyarticular JIA, and 4 ERA) had ongoing active arthritis. Furthermore, all except one of the patients had remission of ophthalmologic findings. No life-threatening adverse events were observed., Conclusions: ABP 501 has a gradual increase in prescription in pediatric rheumatology. Real-life data of the cohort announce that ADL biosimilar is a suitable and effective treatment option for patients with JIA in case of indication.

Background: A wide variety of effects of irisin, as a myokine and adipokine, have been reported. Although there are some clues about its role in the modulation of immune response in the pathogenesis of immune-mediated diseases such as psoriasis, it has not yet been clearly elucidated. The aim of the present study is to investigate the relationship of irisin levels with inflammation and insulin resistance in patients with psoriasis., Methods: This study was conducted in patients with moderate-to-severe psoriasis and healthy subjects who were admitted to Haseki Training and Research Hospital. In addition to routine laboratory analyses, hs-CRP, insulin, irisin, adiponectin, and leptin levels were measured. The association between irisin levels and study variables was assessed using univariate and multivariate analyses., Results: A total of 42 non-diabetic patients with moderate-to-severe psoriasis and 43 healthy subjects were enrolled. The mean irisin, waist circumference, insulin, insulin resistance, and hs-CRP, and frequency of metabolic syndrome were significantly higher in psoriasis patients than healthy controls. Psoriasis and control groups were similar in terms of adiponectin, leptin, and Body Mass Index levels. Also, hs-CRP levels were positively and strongly correlated with irisin, adiponectin, and leptin levels. The median irisin level was 2.15 µg/mL. In the binary logistic regression analysis, CRP level (OR=1.14, 95% CI 1.005-1.29, P=0.042) and a BMI>30 kg/m2 (OR=5.9, 95% CI 1.02-34.4, P=0.048) were independent predictors of a higher irisin level., Conclusions: This study demonstrates that serum irisin levels are higher in patients with moderate-to-severe psoriasis than in healthy subjects. Irisin seems to be associated with inflammation, as measured by hs-CRP. More comprehensive studies are needed to clarify the effect of irisin, on immune-modulate response in patients with psoriasis.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% ( n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EB declared a past co-authorship with several of the authors KÖ, EB, HS, GY, FÇ, SK, SO, FD, MÇ, NA, and BS and reviewer ES declared a past collaboration with several of the authors HS, SK, SO, FD, NA, and BS to the handling editor at the time of the review., (Copyright © 2022 Öztürk, Coşkuner, Baglan, Sönmez, Yener, Çakmak, Demirkan, Tanatar, Karadag, Ozdel, Demir, Çakan, Aktay Ayaz and Sözeri.)

Parkinson's disease (PD), which is a slowly progressing neurodegenerative disorder, negatively affects people's daily lives. Early diagnosis is of great importance to minimize the effects of PD. One of the most important symptoms in the early diagnosis of PD disease is the monotony and distortion of speech. Artificial intelligence-based approaches can help specialists and physicians to automatically detect these disorders. In this study, a new and powerful approach based on multi-level feature selection was proposed to detect PD from features containing voice recordings of already-diagnosed cases. At the first level, feature selection was performed with the Chi-square and L1-Norm SVM algorithms (CLS). Then, the features that were extracted from these algorithms were combined to increase the representation power of the samples. At the last level, those samples that were highly distinctive from the combined feature set were selected with feature importance weights using the ReliefF algorithm. In the classification stage, popular classifiers such as KNN, SVM, and DT were used for machine learning, and the best performance was achieved with the KNN classifier. Moreover, the hyperparameters of the KNN classifier were selected with the Bayesian optimization algorithm, and the performance of the proposed approach was further improved. The proposed approach was evaluated using a 10-fold cross-validation technique on a dataset containing PD and normal classes, and a classification accuracy of 95.4% was achieved.

Protein N-termini provide unique and distinguishing information on proteolytically processed or N-terminally modified proteoforms. Also splicing, use of alternative translation initiation sites, and a variety of co- and post-translational N-terminal modifications generate distinct proteoforms that are unambiguously identified by their N-termini. However, N-terminal peptides are only a small fraction among all peptides generated in a shotgun proteome digest, are often of low stoichiometric abundance, and therefore require enrichment. Various protocols for enrichment of N-terminal peptides have been established and successfully been used for protease substrate discovery and profiling of N-terminal modification, but often require large amounts of proteome. We have recently established the High-efficiency Undecanal-based N-Termini EnRichment (HUNTER) as a fast and sensitive method to enable enrichment of protein N-termini from limited sample sources with as little as a few microgram proteome. Here we present our current HUNTER protocol for sensitive plant N-terminome profiling, including sample preparation, enrichment of N-terminal peptides, and mass spectrometry data analysis., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Substrate sequence specificity is a fundamental characteristic of proteolytic enzymes. Hundreds of proteases are encoded in plant genomes, but the vast majority of them have not been characterized and their distinct specificity remains largely unknown. Here we present our current protocol for profiling sequence specificity of plant proteases using Proteomic Identification of Cleavage Sites (PICS). This simple, cost-effective protocol is suited for detailed, time-resolved specificity profiling of purified or enriched proteases. The isolated active protease or fraction with enriched protease activity together with a suitable control are incubated with split aliquots of proteome-derived peptide libraries, followed by identification of specifically cleaved peptides using quantitative mass spectrometry. Detailed specificity profiles are obtained by alignment of many individual cleavage sites. The chapter covers preparation of complementary peptide libraries from heterologous sources, the cleavage assay itself, as well as mass spectrometry data analysis., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

A large variety of enrichment procedures for protein N-termini have been developed to trace protease activity and determine precise cleavage sites, as well as other N-terminal protein modifications. Typically, enriched N-terminal peptides are identified by tandem mass spectrometry using standard database search engines, in many cases the popular MaxQuant software package. MaxQuant Advanced N-termini Interpreter (MANTI) is a software package that helps to validate, annotate, and visualize peptide identifications in N-termini datasets in a rapid and straightforward manner. Usage of MANTI and especially its graphical interface Yoğurtlu MANTI in detail are described to enable users to take full advantage of the software package and the multitude of options it has to offer., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

We report a case of a right ventricular outpouching diagnosed during prenatal period. We defined it as an aneurysm because of its thin, hypokinetic wall, and wide neck connecting to the ventricle. Ventricular aneurysms, especially right ventricular aneurysms, are very rare cardiac malformations. Therefore, we describe a rare case of right ventricular aneurysm and the diagnostic features, differential diagnosis, and clinical features of ventricular aneurysms.

Aim: To histopathologically evaluate and compare bone morphogenetic protein (BMP)-2, vascular endothelial growth factor (VEGF), and vitamin D receptor (VDR) levels in the ligamentum flavum (LF) of patients with lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH)., Material and Methods: Surgical specimens of the LF in 25 patients who underwent surgery for LDH and 25 patients who underwent surgery for LSS were examined histopathologically. The prevalence and severity of BMP-2, VEGF, and VDR immunoreactivity were evaluated to create histoscores (prevalence × severity), which were compared between groups., Results: The mean BMP-2 histoscore was similar in both groups. In the LSS group, the mean VEGF histoscore was significantly higher and the mean VDR histoscore was significantly lower., Conclusion: Elevated VEGF and decreased VDR levels in the LF in LSS are associated with more intense inflammation and chronic process of the disease. The prominent expression of BMP-2 in the LF in both diseases suggests that BMP-2 might be affected by inflammation regardless of chronic pressure and degeneration.

The new type of coronavirus disease, which has spread from Wuhan, China since the beginning of 2020 called COVID-19, has caused many deaths and cases in most countries and has reached a global pandemic scale. In addition to test kits, imaging techniques with X-rays used in lung patients have been frequently used in the detection of COVID-19 cases. In the proposed method, a novel approach based on a deep learning model named DeepCovNet was utilized to classify chest X-ray images containing COVID-19, normal (healthy), and pneumonia classes. The convolutional-autoencoder model, which had convolutional layers in encoder and decoder blocks, was trained by using the processed chest X-ray images from scratch for deep feature extraction. The distinctive features were selected with a novel and robust algorithm named SDAR from the deep feature set. In the classification stage, an SVM classifier with various kernel functions was used to evaluate the classification performance of the proposed method. Also, hyperparameters of the SVM classifier were optimized with the Bayesian algorithm for increasing classification accuracy. Specificity, sensitivity, precision, and F-score, were also used as performance metrics in addition to accuracy which was used as the main criterion. The proposed method with an accuracy of 99.75 outperformed the other approaches based on deep learning., Competing Interests: Conflict of interestThe authors declare that there is no conflict to interest related to this paper., (© Ohmsha, Ltd. and Springer Japan KK, part of Springer Nature 2022.)

Background: Although not validated fully, recommendations are present for diagnosis, screening and treatment modalities of patients with familial Mediterranean fever (FMF)., Objective: To review the current practices of clinicians regarding FMF and reveal their adherence to consensus guidelines., Methods: Fifteen key points selected regarding the diagnosis and management of FMF were assessed by 14 paediatric rheumatologists with a three-round modified Delphi panel., Results: Consensus was reached on the following aspects: genetic analysis should be ordered to all patients when clinical findings support FMF, but its result is not decisive alone. In the absence of clinical features, colchicine should be commenced when two pathogenic alleles and family history of amyloidosis are present. Serum amyloid A testing at each visit is recommended in patients resistant to colchicine, with subclinical inflammation and family history of amyloidosis. Consensus was reached on both the definition of colchicine resistance and starting biologic in resistant cases. Cost, efficiency, ease of use, treatment adherence, accessibility and emergence of adverse events are the factors affecting the choice of biologic agents. In patients without any attack and evidence of subclinical inflammation within the last 6 months following initiation of biologics, treatment dose intervals can be prolonged., Conclusion: A consensus was achieved regarding the routine diagnosis and screening and treatment of FMF patients. The definition of colchicine resistance was made and a protocol was created for prolongation of treatment intervals of biologic agents. We anticipate that the results of the study reveal real-life data on the approach to patients in clinical practice., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Adherence to treatment is important in chronic dermatological diseases. There are limited data regarding the adherence to treatment in patients with psoriasis during the COVID-19 pandemic., Aims: We aimed to determine the rates of adherence to systemic treatments in patients with psoriasis and to identify the causes of non-adherence during the COVID-19 pandemic., Methods: We conducted a cross-sectional multicenter study from May 2021 to August 2021. A questionnaire including items regarding sociodemographic characteristics of the patients, disease-related characteristics, and treatment-related characteristics were filled out by the physicians. The Psoriasis Area Severity Index (PASI), Hospital Anxiety, and Depression Scale, and the Dermatology Life Quality Index were calculated. The rate of adherence and non-adherence to treatment and reasons for non-adherence to treatment were examined., Results: A total of 342 patients with psoriasis were included (182 male/160 female) in the study. The mean age of the patients was 45.9 ± 14.2 years. The average duration of psoriasis was 192 ± 134.7 months. While the rate of adherence to treatment was 57.6%, the rate of non-adherence to treatment was 42.4%. There were no significant differences with respect to adherence to treatment in comparison with oral and injection-therapy groups. The most frequent reasons for non-adherence to treatment were inability to go to the hospital (19.2%), concern about the COVID-19 infection (16.3%), discontinuation of the treatment by the doctor (13.7%), inability to reach the doctor (7.3%), and inability to have access to the medication (7.3%)., Conclusion: Adherence to oral and injection therapies was fairly high among our patients with psoriasis during the COVID-19 pandemic. Psoriasis severity and duration of medication use had a negative impact on adherence to treatment., (© 2021 Wiley Periodicals LLC.)

Background and Aims: Appendiceal neoplasms are uncommon entities that are usually determined incidentally during the histopathological examination. Different techniques used for the macroscopic sampling of appendectomy material may affect the determinating neoplasms., Materials and Methods: H&E-stained slides of 1280 cases who underwent appendectomy between 2013 and 2018 were reviewed retrospectively for histopathological features., Results: Neoplasms were determined in 28 cases (3.09%); 1 lesion was observed in the proximal part of the appendix, 1 covering the entire length from proximal to distal and 26 in the distal part. In the 26 cases that observed in the distal part, the lesion was seen on both sides of the longitudinal section of the distal appendix in 20 cases, while it was seen on only one distal longitudinal section in the remaining 6 cases., Conclusion: The vast majority of appendiceal neoplasms are seen in the distal part of the appendix, and, in some cases, neoplasms might be seen on only one side of the distal section. Sampling only one-half of the distal part of the appendix, where tumours are most often observed, could result in some neoplasms being missed. Therefore, sampling the whole distal part would be more beneficial to determine small diameter tumours that do not create macroscopic findings., (© The Author(s) 2021. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Changes in and around anatomical structures such as blood vessels, optic disc, fovea, and macula can lead to ophthalmological diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration (AMD), myopia, hypertension, and cataracts. If these diseases are not diagnosed early, they may cause partial or complete loss of vision in patients. Fundus imaging is the primary method used to diagnose ophthalmologic diseases. In this study, a powerful R-CNN+LSTM-based approach is proposed that automatically detects eight different ophthalmologic diseases from fundus images. Deep features were extracted from fundus images with the proposed R-CNN+LSTM structure. Among the deep features extracted, those with high representative power were selected with an approach called NCAR, which is a multilevel feature selection algorithm. In the classification phase, the SVM algorithm, which is a powerful classifier, was used. The proposed approach is evaluated on the eight-class ODIR dataset. The accuracy (main metric), sensitivity, specificity, and precision metrics were used for the performance evaluation of the proposed approach. Besides, the performance of the proposed approach was compared with the existing approaches using the ODIR dataset.

Objective: The aim of this study was to evaluate the dental status and temporomandibular diseases (TMDs)-related symptoms in children with generalized joint hypermobility (GJH) and compare them with healthy controls (HCs)., Methods: This is a cross-sectional, observational study carried out between September 2016 and April 2017. A total of 124 children with GJH (n = 62) and HC (n = 62) were enrolled. The GJH was assessed with the Beighton hypermobility score. The subjects were screened for dental status and TMD-related symptoms. The assessment included the index for "decayed," "missing," and "filled teeth" (DMFT, dmft); plaque; gingival bleeding; tooth mobility; and temporomandibular joint (TMJ) evaluation., Results: The mean Beighton hypermobility score was 6.3 ± 1.2 in the GJH group. Visible plaque index and gingival bleeding index scores were found to be significantly higher in children with GJH then in the HC (p = 0.031, p = 0.023). No differences were found regarding the DMFT scores between the groups (p = 0.16). Temporomandibular disorder-related symptom frequencies were significantly higher in children with GJH (p < 0.001). The most common clinically determined sign of TMD was clicking with a maximum active mouth-opening. Combined TMJ symptoms and TMD were observed in approximately one third of the children with GJH., Conclusions: The presence of GJH in a child may be indicative of future dental or TMJ problems, and it may cause dental problems due to increased gingival bleeding index and visible plaque index scores. Therefore, children with GJH require preventive dental and TMJ care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities., Methods: A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed., Results: LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment ( p = 0.002), the presence of subacute cutaneous findings ( p = 0.007), and the presence of proteinuria ( p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 ( p <0.001)., Conclusion: Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

Objectives: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition resulting in excessive response of the immune system after SARS-CoV-2 infection. We report a single-center cohort of children with MIS-C, describing the spectrum of presentation, therapies, clinical course, and short-term outcomes., Methods: This is a prospective observational study from to a tertiary pediatric rheumatology center including patients (aged 1 month to 21 years) diagnosed with MIS-C between April 2020-April 2021. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed., Results: A total of 67 patients with MIS-C were included in the study. Fever was detected in all patients; gastrointestinal system symptoms were found in 67.2% of the patients, rash in 38.8%, conjunctivitis in 31.3%, hypotension in 26.9% myocarditis, and/or pericarditis in 22.4%, respectively. Respiratory symptoms were only in five patients (7.5%). Kawasaki Disease like presentation was found 37.3% of the patients. The mean duration of hospitalization was 11.8 7.07 days. Fifty-seven patients (85%) received intravenous immunoglobulin (IVIG), 45 (67%) received corticosteroids, 17 (25.3%) received anakinra, and one (1.5%) received tocilizumab. Seven of the patients (10.4%) underwent therapeutic plasma exchange (TPE). In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4-11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7-15 days)., Conclusion: Patients with MIS-C may have severe cardiac findings and intensive care requirements in admission and hospital follow-up. The vast majority of these findings improve with effective treatment without any sequelae until discharge and in a short time in follow-up. Although the pathogenesis and treatment plan of the disease are partially elucidated, follow-up studies are needed in terms of long-term prognosis and relapse probabilities.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement ( p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-β2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings ( p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-β2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Background: The rate of cosmetic procedures and use of skincare products is considered to be affected during the pandemic period; however, this has not been investigated yet., Objective: To determine whether the ongoing pandemic has changed people's habits related to skincare products and cosmetic procedures., Methods: We conducted a multicenter survey study covering both private and public hospitals. Sociodemographic characteristics and clinical diagnoses of the patients were noted by dermatologists. A survey was used to determine the type and application areas of skincare products and cosmetic procedures before and during the pandemic, whether the patients were concerned about being infected, and any change in the make-up habits of female patients., Results: Of the 1437 patients, 86.7% presented to the hospital due to dermatological complaints and 13.3% for cosmetic procedures. The rate of those that did not use skincare products was 0.05% before and 0.06% during the pandemic. Of the participants, 43.2% had undergone cosmetic procedures before and 38.1% during the pandemic. For both periods, the most frequent cosmetic procedure applied was laser epilation, followed by skincare treatment and chemical peeling. While undergoing these procedures, 34.9% of the patients were concerned about contracting coronavirus., Conclusion: There was no significant difference in the use of skincare products and cosmetic procedures before and during the pandemic. The majority of the patients continued to undergo these procedures despite their fear of being infected. This shows that during the pandemic period, patients are concerned with their appearance and continue to undergo cosmetic procedures and pay attention to their skincare., (© 2021 Wiley Periodicals LLC.)

Protein modification by enzymatic breaking and forming of peptide bonds significantly expands the repertoire of genetically encoded protein sequences. The dual protease-ligase legumain exerts the two opposing activities within a single protein scaffold. Primarily localized to the endolysosomal system, legumain represents a key enzyme in the generation of antigenic peptides for subsequent presentation on the MHCII complex. Here we show that human legumain catalyzes the ligation and cyclization of linear peptides at near-neutral pH conditions, where legumain is intrinsically unstable. Conformational stabilization significantly enhanced legumain's ligase activity, which further benefited from engineering the prime substrate recognition sites for improved affinity. Additionally, we provide evidence that specific legumain activation states allow for differential regulation of its activities. Together these results set the basis for engineering legumain proteases and ligases with applications in biotechnology and drug development., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Drug survival is useful to evaluate long-term drug performance in daily practice. The aim of this study was to evaluate drug survival for methotrexate (MTX) monotherapy in patients with plaque-type psoriasis., Methods: We reviewed 3,512 follow-up charts of patients with psoriasis at five tertiary referral centers between January 2012 and January 2020. We analyzed baseline data and treatment outcomes of patients under MTX monotherapy. Drug survival was analyzed using Kaplan-Meier and Cox regression analyses., Results: Patients with psoriasis who were treated with MTX monotherapy were enrolled (N = 649). The median duration of drug survival was 15 months (95% CI: 13.2-16.8). The overall drug survival rate was 54.7%, 17.4%, and 8% after 1, 3, and 5 years, respectively. The main reasons for discontinuation were adverse effects (n = 209, 32.2%) and inefficacy (n = 105, 15.6%). Based on multivariate Cox regression analysis, the presence of nausea/vomiting (HR: 2.01, 95% CI: 1.49-2.71; P < 0.001) was observed as a statistically significant risk factor for drug discontinuation. Age over 50 years (HR: 0.68, 95% CI: 0.48-0.97; P = 0.03) and using MTX dose ≥15 mg/weekly were positive predictors for drug survival (HR: 0.72, 95% CI: 0.54-0.95; P = 0.02)., Conclusions: The average drug survival of MTX was 15 months. MTX is still the first-line treatment of moderate-to-severe plaque psoriasis, as highlighted in guidelines. To prevent premature discontinuation, physicians need to look at the response time of at least 16-24 weeks, especially when a stepwise dose increment is used. The presence of nausea/vomiting seemed to be associated with an approximately twofold risk of discontinuation., (© 2021 the International Society of Dermatology.)

Background: The glomerulus comprises podocytes, mesangial cells, and endothelial cells, which jointly determine glomerular filtration. Understanding this intricate functional unit beyond the transcriptome requires bulk isolation of these cell types for biochemical investigations. We developed a globally applicable tripartite isolation method for murine mesangial and endothelial cells and podocytes (timMEP)., Methods: We separated glomerular cell types from wild-type or mT/mG mice via a novel FACS approach, and validated their purity. Cell type proteomes were compared between strains, ages, and sex. We applied timMEP to the podocyte-targeting, immunologic, THSD7A-associated, model of membranous nephropathy., Results: timMEP enabled protein-biochemical analyses of podocytes, mesangial cells, and endothelial cells derived from reporter-free mice, and allowed for the characterization of podocyte, endothelial, and mesangial proteomes of individual mice. We identified marker proteins for mesangial and endothelial proteins, and outlined protein-based, potential communication networks and phosphorylation patterns. The analysis detected cell type-specific proteome differences between mouse strains and alterations depending on sex, age, and transgene. After exposure to anti-THSD7A antibodies, timMEP resolved a fine-tuned initial stress response, chiefly in podocytes, that could not be detected by bulk glomerular analyses. The combination of proteomics with super-resolution imaging revealed a specific loss of slit diaphragm, but not of other foot process proteins, unraveling a protein-based mechanism of podocyte injury in this animal model., Conclusion: timMEP enables glomerular cell type-resolved investigations at the transcriptional and protein-biochemical level in health and disease, while avoiding reporter-based artifacts, paving the way toward the comprehensive and systematic characterization of glomerular cell biology., (Copyright © 2021 by the American Society of Nephrology.)

Objective: The objective of the study was to describe the findings of pediatric patients diagnosed with COVID-19 in computed tomography (CT) and chest X-ray (CXR) images. Therefore, the aim of this study is to show protecting the children from radiation as much as possible while guiding the diagnosis., Methods: Between March and June 2020, 148 pediatric patients examined who underwent CT due to suspicion of COVID-19. Fifty patients of 148 with normal thorax CT and negative reverse transcription polymerase chain reaction (RT-PCR) were excluded from the study. Of the remaining 98 patients were evaluated retrospectively by two pediatric radiologists with 15 years of experience., Results: The demographic, clinical, and laboratory data were evaluated for 52 RT-PCR-positive patients. CT finding of 23 RT-PCR positive and 12 negative patients was classified. According to our study, unilateral (61-67%), multifocal (50-52%), and peripheral (83-91%) involvement were higher in all groups. Lower lobe involvement was frequently detected (58-65%). The most frequently detected parenchymal lesion was ground-glass opacity followed by consolidated areas accompanying ground-grass opacities. Halo sign and vascular enlargement signs were the common signs of lung lesions (35%). In addition, some rare findings not previously described in this disease in children were mentioned in this study. The clinical course of all our patients was mild and control radiological imaging checked by CXR., Conclusion: Most pediatric patients have a mild course. Hence, a balance between the risk of radiation and necessity for chest CT is very important. Low-dose CT scan is more suitable for pediatric patients but still it should be used cautiously., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2021 by Istanbul Northern Anatolian Association of Public Hospitals.)

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder that is characterized by a triad of microthrombocytopenia, severe immunodeficiency, and eczema. We report the case of a 7-year-old male patient with chronic thrombocytopenia that was diagnosed as WAS after dilatation of the ascending aorta was noticed. WAS is rare, and it is a disease that requires high suspicion for diagnosis. We recommend periodic echocardiography and magnetic resonance imaging examinations to evaluate aortic aneurysms in children with WAS and that surgical intervention should not be delayed when aneurysm is detected., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Proteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic systems in inflammatory kidney disease. Inflammatory kidney diseases are associated with broad dysregulations of extracellular and intracellular proteolysis. As an example of a proteolytic system, the complement system plays a significant role in glomerular inflammatory kidney disease and is currently under clinical investigation. Based on two glomerular kidney diseases, lupus nephritis, and membranous nephropathy, we portrait two proteolytic pathomechanisms and the role of the complement system. We discuss how profiling proteolytic activity in patient samples could be used to stratify patients for more targeted interventions in inflammatory kidney diseases. We also describe novel comprehensive, quantitative tools to investigate the entirety of proteolytic processes in a tissue sample. Emphasis is placed on mass spectrometric approaches that enable the comprehensive analysis of the complement system, as well as protease activities and regulation in general., (© 2021. The Author(s).)

Objective: Takayasu arteritis is a rare granulomatous chronic vasculitis that affects the aorta and its main branches. Neurologic manifestations can accompany the disease; however, there is no study on neuroimaging in children with Takayasu arteritis. Therefore, we aimed to evaluate cranial magnetic resonance imaging (MRI) in pediatric Takayasu arteritis patients., Materials and Methods: Demographic, clinical, and laboratory data were obtained retrospectively., Results: The study included 15 pediatric Takayasu arteritis patients. All patients presented with constitutional symptoms. Additionally, 6 patients suffered from headache, 2 had syncope, 1 had loss of consciousness, and 1 had convulsion. All patients underwent cranial and diffusion MRI a median 12 months after diagnosis. Cranial MRI findings were normal in 12 patients, whereas 3 patients had abnormal findings, as follows: stenosis in the M1 and M2 segments of the left middle cerebral artery (n = 1); diffuse thinning of the right internal carotid, middle cerebral, and right vertebral and basilar artery (n = 1); as a sequela, areas of focal gliosis in both the lateral ventricular and posterior periventricular regions (n = 1). Among these 3 patients, 1 had no neurologic complaints., Conclusion: Abnormal MRI findings can be observed in pediatric Takayasu arteritis patients, even those that are asymptomatic; therefore, clinicians should carefully evaluate neurologic involvement in all pediatric Takayasu arteritis patients.

Background and Aims: The Friedewald equation (LDL-Cf) is known to produce inaccurate estimations of low-density lipoprotein cholesterol (LDL-C) when triglycerides are high (>400 mg/dL) or LDL-C is low (<70 mg/dL). The Martin/Hopkins (LDL-Cmh) and Sampson (LDL-Cs) equations were developed to overcome these limitations, but few data are available to assess whether these equations offer incremental usefulness over LDL-Cf. Our aim was to understand whether there was any incremental usefulness of novel equations on decisions regarding patient management., Methods: Four thousand one hundred and ninety-six cardiology patients who were included in a multicentre registry database were analysed. Each patient was assigned to a cardiovascular risk class using the SCORE (Systematic COronary Risk Evaluation) algorithm, and relevant European guidelines were used to assess LDL-C targets., Results: Compared with LDL-Cmh and LDL-Cs, LDL-Cf was able to correctly identify 96.9%-98.08% of patients as within or outside the LDL-C target, respectively, and 1.95%-2.8% of patients were falsely identified as being within the LDL-C target. Kappa coefficients for agreement between LDL-Cf vs LDL-Cmh and LDL-Cf vs LDL-Cs were 0.868 and 0.918 (P < .001). For patients not on cholesterol-lowering drugs, the decision to initiate treatment would be different in 1.2%-1.8% of cases if LDL-Cs or LDL-Cmh were used, respectively. For those already on cholesterol-lowering drugs, decisions regarding treatment intensification would be different in 1.5%-2.4% of cases if LDL-Cs or LDL-Cmh were used., Conclusions: In most cardiology outpatients, the Friedewald equation has excellent agreement with the novel Martin/Hopkins and Sampson equations, and treatment decisions should not change in most patients., (© 2021 John Wiley & Sons Ltd.)