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Aim of the Study: to determine the frequency of joint lesions (JnL) in children with juvenile localized scleroderma and it's possible correlation with autoantibodies and markers of fibrosis., Materials and Methods: 500 children with JLS (370 girls and 130 boys) were studied retrospectively for the joint lesion, using standard physical examination, ultrasound examination (UlS) X-ray, MRI. In 190 patients we investigated antinuclear antibodies (antinuclear factor (ANF), rheumatoid factor (RF), antitopoisomerase 1 and anticentomere antibodies, antibodies to DNA, autoantibodies to collagen (Cab) types I-IV, cryoglobulins (CG), serum fibronectine (FN) and hyalyronic acid (HA) levels., Results: JLS patients were divided into 4 groups:124 patients with circumscribed morphea, 259- linear scleroderma, 93- generalized morphea, pansclerotic in 1 patient, mixed morphea - 23 patients. JnL were noticed in 175 patients (35%), among them the majority 151 patient (86%) with linear and unilateral forms of JLS. JnL were presented by joint pain in 47% of patients, limitation of joint movement in 60% of affected patients, mostly due to periarticular induration or tissue fibrosis. UlS showed joint effusions - in 16% of JnL, sinovitis and tenosinivitis in 45%. In 12 children joint space narrowing was detected by X ray, in 2-articular erosions. MRI was performed in 97 patients with limitation of joint movement, active synovitis, tenosynovitis found in 80 children. In 1 girl with unilateral scleroderma MRI with contrasting visualised avascular osteonecrosis of tibia. The absolute percentage of positive values detected autoantibodies and fibrosis markers was higher in children with JnL. ANF was detected in 56 % and RF in 28,4 % of patients with JnL, while sclerodermo specific antibodies and ds-DNA were detected in small percentage of JnL patients and in none without it. The levels of CG, FN, HA and Cab were elevated in patients with JnL. Cab of type I and type II were detected in most cases of JnL patients (71% and 62% correspondingly)., Conclusion: JnL occurs in 35% of JLS patients, predominantly in linear and unilateral forms of the disease. Detection of autoantibodies and fibrosis markers in 27-56% of JnL cases demonstrates the activity of autoimmune inflammation and justificates early systemic immunosuppressive therapy in JLS.

Objective: To investigate the spectrum of neurological disorders in children with juvenile localized scleroderma (JLS) on face and JLS without plaques on face and head., Materials and Methods: 156 children with JLS were examined were with a neurological examination MRI, EEG, genetic thrombophilia markers detection., Results: Neurological disorders (ND) were found in 56 from 114 (49%) of the patients with scleroderma of head and face (LSH)(group1) and in 30% (13 from 42) with JLS without plaques on face (Group 2). Headaches were detected in Group 1 in 43,8%, in Group 2-in30%. In Group 1 other disorders were detected: epileptic seizures (in 25%), cranial nerve involvement (12.5%), stroke (5.3%), tics (5.3%), none of named in Group 2. Out of 56 children with ND changes on brain magnetic resonance imaging (MRI) were detected in 47 (84%). white matter lesions and less commonly gliotic changes in the periventricular area. Electroencephalography (EEG) monitoring revealed typical patterns of epileptiform activity in the majority of cases. These three cases of ischemic stroke in children with LSH are the first to be presented. All patients with stroke were diagnosed with genetic thrombophilia, two had cerebral vascular malformations, and one had antiphospholipid syndrome., Conclusion: Our data suggest that sclerodermic vasculopathy, cerebral vascular anomalies and genetic thrombophilia are rick factors for stroke in children with LSH. Mandatory MRI angiography and screening for genetic thrombophilia could identify risk group for stroke in children with LSH.

The effect of silver nanoparticles (Ag NPs) obtained in the presence of royal jelly (RJ) on the growth of yeast Candida guilliermondii NP-4, on the total and H + -ATPase activity, as well as lipid peroxidation process and antioxidant enzymes (superoxide dismutase (SOD), catalase) activity was studied. It has been shown that RJ-mediated Ag NPs have a fungicide and fungistatic effects at the concentrations of 5.4 µg mL -1 and 27 µg mL -1 , respectively. Under the influence of RJ-mediated Ag NPs, a decrease in total and H + -ATPase activity in yeast homogenates by ~ 90% and ~ 80% was observed, respectively. In yeast mitochondria total and H + -ATPase activity depression was detected by ~ 80% and ~ 90%, respectively. The amount of malondialdehyde in the Ag NPs exposed yeast homogenate increased ~ 60%, the catalase activity increased ~ 70%, and the SOD activity-~ 30%. The obtained data indicate that the use of RJ-mediated Ag NPs have a diverse range of influence on yeast cells. This approach may be important in the field of biomedical research aimed at evaluating the development of oxidative stress in cells. It may also contribute to a more comprehensive understanding of antimicrobial properties of RJ-mediated Ag NPs and help control the proliferation of pathogenic fungi., (© 2024. The Author(s).)

Linear scleroderma of head and face (LSH) in children is a severe disorder, that results in hemiatrophy of skin, subcutaneuse tissue, bones with functional disabilities, neurologic disorders and uveal involvement. The aim of the research was to establish uveal involvement in children with hemifacial scleroderma. Materials and methods: A retrospective analysis was done in a group of 110 children with hemifacial scleroderma. A comprehensive clinical, laboratory and instrumental examination was performed, including MRI of the brain, EEG, and an ophthalmologist's examination, which included visometry, biomicroscopy, and ophthalmoscopy. Results: 10 cases of uveal involvement were detected (9% of 110 pt). 9 patients had anterior segment inflammation (iridocyclitis), in 2 iridocyclitis was combined with retinal changes (in 1- peripheral focal chorioretinitis, in 1- iridocyclitis and central focal chorioretinitis). In one case, iridocyclitis was combined with optic neuropathy. In 3 children uveitis appeared at the disease debute, in the others 3-10 years later. Uveal inflammation in all cases was on the side of scleroderma skin involvement. In 3 children uveitis was bilateral. Seizures and concomittant foci in white matter of the brain were detected in 2 children with uveitis. 90% of the group had positive antinuclear factor. Persistent decrease in visual acuity developed in 3 patients. Соnclusion: Patients with LSH must undergo routine eye examination using basic ophthalmological techniques (visometry, biomicroscopy, ophthalmoscopy) every 6 months and highly necessary in case of relapse of scleroderma We assume that patients with UI in LSH must be defined as patients with JSS and treated intensively with systemicglucocorticoids, cytostatics and even biologics in case of resistance.

Purpose: Prosthetics for patients after oncological resection of the upper jaw is a complex problem associated with the physiological and anatomical separation of the oral cavity and the nasal/paranasal region. This study reports the clinical results of the use of the zygomatic implants for prosthetic rehabilitation in patients with maxillectomy due to upper jaw tumors., Materials and Methods: The study included 16 patients who underwent prosthetic rehabilitation using a zygomatic implant after maxillectomy period from 2021 to 2023. After the tumor was removed, immediate surgical obturators were placed. Main prosthetic rehabilitation was performed 6-12 months after tumor removal, but before that, a temporary obturator was made and used. Six-twelve months after tumor resection, 1-4 zygomatic implants were inserted into the zygomatic bone unilaterally or bilaterally. A total of 42 zygomatic implants were installed, 2 of which were unsuccessful and were removed in 1 patient. The implants were placed using the surgical guide, which was planned and prepared digitally., Results: No postsurgical complications were seen, and the patients were discharged from the hospital after 7-10 days. The patients were able to return to a normal diet (hard food) after just 7 days following surgery, with no further complaints regarding function or pain, apart from the residual edema caused by the intervention., Conclusions: The use of prostheses fixed on zygomatic implants in patients with maxillary defects is an effective method of prosthodontic rehabilitation in complex clinical cases after maxillectomy., (© 2024. The Author(s).)

The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m 2 /day for 7 days and 21 days at a dose of 15 μg/m 2 /day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ ETV6::RUNX1 became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate and assess the indicators of bone metabolism markers osteocalcin and β -Cross-Laps in blood serum as a tool for monitoring bone regeneration and determining the time of implantation in patients after mandibulectomy and reconstruction of a free fibular flap with subsequent endosteal implants., Materials and Methods: Forty-eight patients in a 6-year period participated in this study, due to resection for tumors. All patients underwent reconstruction with fibula free flap after tumor resection, 4-6 months after osteoectomy, dental implants were installed with further orthopedic rehabilitation. To assess the rate of bone remodeling after transplantation, the content biochemical markers of bone remodeling osteocalcin and β -Cross-Laps serum were determined by enzyme immunoassay., Results: All 46 fibular free flaps were healed without complications and were survived. A total 326 implants installed, 8 implants failed to osseointegrate, and 6 implants failed after 5 years of loading (peri-implantitis). Success rate of implants after 5 years was 95,7%. In patients before surgery, the mean of osteocalcin levels was 8.5 ng/ml, two months later, there was a sharp increase in the content of osteocalcin by 15.4 ng/ml, after four months reached 24.7 ng/ml, after six months of 28.6 ng/ml, then the indicator began to decrease and after 12 months it was approaching the norm of 14.7 ng/ml. In patients before surgery, the mean level of β -Cross-Laps was 0.76 ng/ml, after two months bone transplantation the mean level of β -Cross-Laps decreased to - 0.65 ng/ml, after four months the indicator increased and reached of 0.98 ng/ml, after six months the indicator was - 1.56 ng/ml, then these indicators began to decrease and after 12 months, approaching normal values of - 0.87 ng/ml. There is a correlation between different concentrations of osteocalcin or β -Cross- Laps and the success rate of implants. Implants were shown to be unsuccessful low concentrations of osteocalcin and high concentrations of β -Cross-Laps in serum., Conclusion: Studies have shown that the long-term survival and success rates of implants placed in the reconstructed areas may guarantee an excellent prognosis of implant-supported prostheses. Bone markers in blood serum osteocalcin and β -Cross-Laps can be used to evaluate the rate of bone remodeling, which allows you to determine the time of implantation., Competing Interests: Conflict of interestThe author declares that he has no conflict of interest and there was no external source of funding for the present study. None of the authors have any relevant financial relationship(s) with a commercial interest., (© The Association of Oral and Maxillofacial Surgeons of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: In recent years, several studies have reported on the relationship between diabetes and carpal tunnel syndrome (CTS). However, due to their contradictory results, a systematic review and meta-analysis were conducted to investigate this subject., Methods: This study is a systematic review and meta-analysis of studies published in ISI Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase databases. Heterogeneity in the studies included in the meta-analysis was evaluated using statistical tests such as the Chi-square test, I2, and forest plots. Publication bias was assessed using Begg's and Egger's tests., Results: This investigation analyzed data from 42 studies conducted between 1985 and 2022, with a total of 3,377,816 participants. The meta-analysis demonstrated that the odds ratio (OR) of CTS in participants with a history of diabetes compared to those without was 1.90 (95% CI: 1.64-2.21; P-value < 0.001). Given that publication bias was observed in this study (Begg's test P-value = 0.01), the modified OR was calculated with consideration of missed studies, which was 1.68 (95% CI: 1.45-1.94; P-value < 0.001)., Conclusion: The results of this study suggest that diabetic patients have 90% higher odds of developing CTS compared to non-diabetic individuals, which is statistically significant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sanjari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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The present research is primarily focused on investigating the characteristics of environmentally persistent free radicals (EPFRs) generated from commonly recognized aromatic precursors, namely, 1,2-dichlorobenzene (DCB) and 2-monochlorophenol (MCP), within controlled laboratory conditions at a temperature of 230 °C, termed as DCB230 and MCP230 EPFRs, respectively. An intriguing observation has emerged during the creation of EPFRs from MCP and DCB utilizing a catalyst 5% CuO/SiO 2 , which was prepared through various methods. A previously proposed mechanism, advanced by Dellinger and colleagues (a conventional model), postulated a positive correlation between the degree of hydroxylation on the catalyst's surface (higher hydroxylated, HH and less hydroxylated, LH) and the anticipated EPFR yields. In the present study, this correlation was specifically confirmed for the DCB precursor. Particularly, it was observed that increasing the degree of hydroxylation at the catalyst's surface resulted in a greater yield of EPFRs for DCB230. The unexpected finding was the indifferent behavior of MCP230 EPFRs to the surface morphology of the catalyst, i.e., no matter whether copper oxide nanoparticles are distributed densely, sparsely, or completely agglomerated. The yields of MCP230 EPFRs remained consistent regardless of the catalyst type or preparation protocol. Although current experimental results confirm the early model for the generation of DCB EPFRs (i.e., the higher the hydroxylation is, the higher the yield of EPFRs), it is of utmost importance to closely explore the heterogeneous alternative mechanism(s) responsible for generating MCP230 EPFRs, which may run parallel to the conventional model. In this study, detailed spectral analysis was conducted using the EPR technique to examine the nature of DCB230 EPFRs and the aging phenomenon of DCB230 EPFRs while they exist as surface-bound o -semiquinone radicals ( o -SQ) on copper sites. Various aspects concerning bound radicals were explored, including the hydrogen-bonding tendencies of o -semiquinone ( o -SQ) radicals, the potential reversibility of hydroxylation processes occurring on the catalyst's surface, and the analysis of selected EPR spectra using EasySpin MATLAB. Furthermore, alternative routes for EPFR generation were thoroughly discussed and compared with the conventional model., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Particulate matter (PM) containing environmentally persistent free radicals (EPFRs) results from the incomplete combustion of organic wastes which chemisorb to transition metals. This process generates a particle-pollutant complex that continuously redox cycles to produce reactive oxygen species. EPFRs are well characterized, but their cardiopulmonary effects remain unknown. This publication provides a detailed approach to evaluating these effects and demonstrates the impact that EPFRs have on the lungs and vasculature. Combustion-derived EPFRs were generated (EPFR lo: 2.1e -16 radical/g, EPFR hi: 5.5e -17 radical/g), characterized, and verified as representative of those found in urban areas. Dry particle aerosolization and whole-body inhalation were established for rodent exposures. To verify that these particles and exposures recapitulate findings relevant to known PM-induced cardiopulmonary effects, male C57BL6 mice were exposed to filtered air, ∼280 μg/m 3 EPFR lo or EPFR hi for 4 h/d for 5 consecutive days. Compared to filtered air, pulmonary resistance was increased in mice exposed to EPFR hi. Mice exposed to EPFR hi also exhibited increased plasma endothelin-1 (44.6 vs 30.6 pg/mL) and reduced nitric oxide (137 nM vs 236 nM), suggesting vascular dysfunction. Assessment of vascular response demonstrated an impairment in endothelium-dependent vasorelaxation, with maximum relaxation decreased from 80% to 62% in filtered air vs EPFR hi exposed mice. Gene expression analysis highlighted fold changes in aryl hydrocarbon receptor (AhR) and antioxidant response genes including increases in lung Cyp1a1 (8.7 fold), Cyp1b1 (9 fold), Aldh3a1 (1.7 fold) and Nqo1 (2.4 fold) and Gclc (1.3 fold), and in aortic Cyp1a1 (5.3 fold) in mice exposed to EPFR hi vs filtered air. We then determined that lung AT2 cells were the predominate locus for AhR activation. Together, these data suggest the lung and vasculature as particular targets for the health impacts of EPFRs and demonstrate the importance of additional studies investigating the cardiopulmonary effects of EPFRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2). A total of 81 anonymized submissions were received between September 2019 and March 2020. Most participants' predictions performed better than random predictions in classifying IBD versus nonIBD, Ulcerative Colitis (UC) versus nonIBD, and Crohn's Disease (CD) versus nonIBD. However, discrimination between UC and CD remains challenging, with the classification quality similar to the set of random predictions. We analyzed the class prediction accuracy, the metagenomics features by the teams, and computational methods used. These results will be openly shared with the scientific community to help advance IBD research and illustrate the application of a range of computational methodologies for effective metagenomic classification., (© 2023. The Author(s).)

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin (hATG) and cyclosporin A (CsA) with (n = 49) or without (n = 49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR + IST and IST groups was similar (65% vs 53%; P = .218); however, the complete response (CR) rate was significantly higher in the ELTR + IST group (31% vs 12%; P = .027). In severity subgroups, the ORR was 89% vs 57% (P = .028) in favor of IST + ELTR in SAA, but it did not differ in patients with vSAA (52% vs 50%; P = .902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared with 17% of initial ELTR(+) patients (P = .016). No significant difference in ELTR + IST and IST groups was observed in the 3-year overall survival (OS) (89% vs 91%; P = .673) or the 3-year event-free survival (EFS) (53% vs 41%; P = .326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. This trial was registered at Clinicaltrials.gov as #NCT03413306., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air pollution, the environmentally persistent free radical (EPFR) DCB230, was used to mimic pollution exposure four hours prior to infection. Some wells were pretreated with antioxidant, astaxanthin, for 24 hours prior to EPFR-DCB230 exposure and/or SARS-CoV-2 infection. Outcomes included viral replication, epithelial integrity, surface receptor expression ( ACE2 , TMPRSS2 ), cytokine mRNA expression ( TNF-α , IFN-β ), intracellular signaling pathways, and oxidative defense enzymes. SARS-CoV-2 infection induced a mild phenotype in NECs, with some cell death, upregulation of the antiviral cytokine IFN-β , but had little effect on intracellular pathways or oxidative defense enzymes. Prior exposure to EPFR-DCB230 increased SARS-CoV-2 replication, upregulated TMPRSS2 expression, increased secretion of the proinflammatory cytokine TNF-α , inhibited expression of the mucus producing MUC5AC gene, upregulated expression of p21 (apoptosis pathway), PINK1 (mitophagy pathway), and reduced levels of antioxidant enzymes. Pretreatment with astaxanthin reduced SARS-CoV-2 replication, downregulated ACE2 expression, and prevented most, but not all EPFR-DCB230 effects. Our data suggest that oxidant damage to the respiratory epithelium may underly the link between poor air quality and increased COVID-19. The apparent protection by antioxidants warrants further research.