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As an alternative to bisphenol A (BPA), bisphenol S (BPS) has been used as an ink developer in thermal paper products including price labels on food packaging which have been suggested as the sources of BPS found at high levels in packaged fish samples. BPS in the printed price labels glued onto the outside of plastic film could migrate indirectly from the printed surface through the paper, adhesive and film into the food. In order to investigate if price labels could also be the sources of BPS detected in the meat samples in our previous studies, meat and other food samples packaged under different conditions were collected, and BPS in these samples together with the price labels on the corresponding packaging were extracted with solvent followed by solid phase extraction and stable isotope dilution LC-MS/MS analysis. BPS was detected at very high levels (161.7-222.4 µg/cm 2 ) in all the five sticker type of price labels, indicating BPS being the dominant if not the sole ink developer. BPS was also detected in all the 26 continuous roll type of price labels but at very low levels (0.017-18 ng/cm 2 ), indicating that the dominant ink developer is likely one of the other alternatives, rather than BPS. Despite BPS being detected in all price labels on packaging of fish, meat, and cheese samples, BPS was not detected or detected in only a few fish, meat, and cheese samples at levels considerably lower than the current EU specific migration limit (SML) of 50 ng/g food for BPS authorised under Regulation (EU) 10/2011.

Aim: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac). We aimed to study whether chronic CsA and Tac exposures, before reaching irreversible nephrotoxic damage, affect renal compartments differentially and whether related pathogenic mechanisms can be identified., Methods: CsA and Tac were administered chronically in wild type Wistar rats using osmotic minipumps over 4 weeks. Functional parameters were controlled. Electron microscopy, confocal, and 3D-structured illumination microscopy were used for histopathology. Clinical translatability was tested in human renal biopsies. Standard biochemical, RNA-seq, and proteomic technologies were applied to identify implicated molecular pathways., Results: Both drugs caused significant albeit differential damage in vasculature and nephron. The glomerular filtration barrier was more affected by Tac than by CsA, showing prominent deteriorations in endothelium and podocytes along with impaired VEGF/VEGFR2 signaling and podocyte-specific gene expression. By contrast, proximal tubule epithelia were more severely affected by CsA than by Tac, revealing lysosomal dysfunction, enhanced apoptosis, impaired proteostasis and oxidative stress. Lesion characteristics were confirmed in human renal biopsies., Conclusion: We conclude that pathogenetic alterations in the renal compartments are specific for either treatment. Considering translation to the clinical setting, CNI choice should reflect individual risk factors for renal vasculature and tubular epithelia. As a step in this direction, we share protein signatures identified from multiomics with potential pathognomonic relevance., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Background: As one of the speculated bisphenols to replace bisphenol A (BPA), bisphenol F (BPF), naturally present in mustard, is structurally similar to BPA and may have similar estrogenic activity, but information on its toxicity is very limited compared to BPA., Objective: In order to support the toxicology study of BPF at Heath Canada, a gas chromatography (GC) with mass spectrometry (MS) method based on solid phase extraction and derivatization was developed for analysis of BPF in liver samples., Methods: Samples were treated with β-glucuronidase to convert BPF glucuronide to free BPF for analysis of total BPF., Results: The method was validated for free BPF at different spiking levels, and recoveries ranged from 90.0-97.5% with relative standard deviations from 0.11-5.54%. The method was also validated for glucuronide-conjugated BPF at different spiking levels of BPF mono-β-D-glucuronide, recoveries ranged from 72.3-93.3% with relative standard deviations from 1.7-8.94%. The method was used to analyse 60 liver tissue samples from the rats dosed with BPF at different levels in a toxicology study. Free and glucuronide-conjugated BPF were not detected in any of the control samples which were not dosed with BPF (average method detection limit: 0.31 ng/g), but detected in all the other liver tissue samples with levels increasing at higher doses. The percent of glucuronide-conjugated BPF in total BPF varied among the liver samples, from as low as 9.8% to as high as 77.9%, indicating the importance of analysing biological samples for BPF in both free and conjugated forms for total exposure., Conclusion: A GC-MS method based on solid phase extraction and derivatization was developed for analysis of both free and glucuronide-conjugated BPF in liver samples. This method was validated not only for free BPF, but also for mono-β-D-glucuronide conjugated BPF for the first time to confirm the efficiency of the deconjugation procedure with enzyme., Highlights: This method can be adapted and applied for analysis of free and glucuronide-conjugated BPF in other biological samples with appropriate validation in target sample matrices., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like fibro-osseous lesion that can develop anywhere in the neuraxis. Approximately a half of reported CAPNONs developed in the spinal region, mostly close to the facet joint (FJ). The diagnosis of spinal CAPNONs is challenging given the existence of mimics and associated pathologies including calcific degeneration of the FJ ligaments (DFJL) and synovial cysts (SCs). The pathogenesis of CAPNON remains elusive, although there have been a few hypotheses including degenerative, reactive, proliferative and immune-mediated processes. Our present study examined clinical, radiological and pathological features of 12 spinal CAPNONs in comparison to 9 DFJL foci, and diagnostic and pathogenic relationship between CAPNONs and FJ pathologies. On imaging, CAPNONs were all tumor-like and typically bigger than DFJL foci. All CAPNONs showed pathologically diagnostic features including characteristic cores, consistently identifiable core-surrounding/peripheral palisading of macrophages and other cells including multinucleated giant cells, variable infiltration of CD8 + T-cells, and multifocal immunopositivity of neurofilament light chain (NF-L). These features were absent or limited in the DFJL foci with statistically significant differences from CAPNONs, except calcifications. Spinal CAPNONs co-existed with DFJL foci in all cases; some had transitional foci with overlapping focal CAPNON and DFJL-like features. These findings, along with our previously reported relationship between CAPNONs and SCs, suggest that spinal CAPNONs may occur in association with or in transition from calcifying/calcified degenerative lesions of FJ ligaments and/or SCs when a reactive proliferative process is complemented by other pathogenic changes such as immune-mediated pathology and NF-L deposition/expression., Competing Interests: Declaration of competing interest Dr. Faiha Fareez has received the Resident Research Grant from Department of Pathology and Molecular Medicine, McMaster University. The other authors receive no funding specified for this work and report no conflicts of interest. Parts of this study have been presented at the 20th International Congress of Neuropathology. Berlin, Germany (September 13–16, 2023), and as an abstract, published in Brain Pathology 2023; 33(S1):189., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Physical fitness is a health marker in youth and is associated with current and future health., Objective: Present the healthy fitness zone (HFZ) prevalence and age-specific fitness profile of young people from seven European countries., Methods: This study used data from the European Fitness Monitoring System project. The sample comprised 4965 (51.4% boys) youths aged 9 to 18 years. Fitness data were collected by physical education teachers using field-based tests. Raw data from the fitness tests were used to calculate the prevalence and 95% confidence intervals (CI) of participants in the HFZ., Results: The overall prevalence of boys and girls in the HFZ for all tests was 16.6% (95% CI = 14.7, 18.1) and 14.9% (95% CI = 13.2, 16.6), respectively. Boys have a mainly positive HFZ profiles, except for the 9-year-olds in the sit and reach (z-score difference = -1.20) and the 20 m run for boys 13-18-year-olds (z-score difference range: -0.09 to -0.01). Girls have worse HFZ profiles than boys, being out of the HFZ in several tests. Furthermore, a decreasing trend in z-score difference from the HFZ with age was observed in VO 2 peak for boys and girls and sit and reach for girls. Notwithstanding, several country-related, sex and age differences were observed., Conclusions: Boys presented mostly healthy age-specific fitness profiles in several fitness tests and ages. These differences should be considered when promoting youth's health through physical activity and fitness, as different fitness levels may require different approaches to implementing health-enhancing physical activity policies., (© 2023 Wiley Periodicals LLC.)

Low testosterone (T), common in aging men, associates with cardiovascular disease. We investigated whether follicle-stimulating hormone (FSH), which is affected by T, modulates the cardiovascular effects associated with low T or castration. FSHβ -/- :low-density lipoprotein receptor (LDLR) -/- mice, untreated or castrated (orchiectomy, gonadotropin-releasing hormone agonist or antagonist), demonstrated significantly less atherogenesis compared with similarly treated LDLR -/- mice, but not following FSH delivery. Smaller plaque burden in LDLR -/- mice receiving gonadotropin-releasing hormone antagonists vs agonists were nullified in FSHβ -/- :LDLR -/- mice. Atherosclerotic and necrotic plaque size and macrophage infiltration correlated with serum FSH/T. In patients with prostate cancer, FSH/T following androgen-deprivation therapy initiation predicted cardiovascular events. FSH facilitates cardiovascular disease when T is low or eliminated., Competing Interests: Financial support was provided by the Heart and Stroke Foundation of Canada, Grant-in Aid (G-18-0022086) to Drs Pinthus and Duivenvoorden, McMaster Surgical Associates grant to Drs Pinthus and Duivenvoorden, and Ferring Pharmaceuticals through an investigator-initiated grant to Dr Pinthus. Ferring Pharmaceuticals had no involvement in study design, collection, analysis, and interpretation of data, writing of the report, or the decision to submit for publication. Dr Pinthus has acted in a consulting role for Ferring Pharmaceuticals, and has received research funding from Ferring Pharmaceuticals for this project. Dr Margel has received research funding from Ferring Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females., (© 2023 Wiley Periodicals LLC.)

With the goal to discover a new antitumor drug with the better or similar effects to existing, a small series of β -diketonate was tested on a cisplatin-resistant MDA-MB-231 and HeLa tumor cell lines, and nontumor MRC-5 cell line. All compounds showed notable cytotoxicity against both tumor cell lines and good selectivity. Importantly, β -diketonates displayed greater selectivity than cisplatin, which is the crucial factor for a new antitumor drug candidate. Further, investigations with biomacromolecules such as DNA and serum albumin were performed. Investigations showed that tested compounds bind to DNA through intercalation and have appropriate affinity for binding to bovine serum albumin. In addition, the molecular docking study was performed to investigate more specifically the sites and binding mode of tested β -diketonate to DNA or bovine serum albumin. In conclusion, all results indicated the big potential of these compounds for application in clinical practice in future.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

It is known that the industry already abandoned the use of bisphenol A (BPA)-based epoxy resins as internal coatings for some canned food products (e.g. infant formula, soups). The presence of bisphenol A (BPA) in foods has also been extensively investigated, especially since late 2000. However, information on temporal trends of BPA occurrence in foods is very limited. It is not clear if BPA-based epoxy resins are still being used in internal coating for many other canned foods and if the overall exposure to BPA through consumption of canned foods has significantly decreased. As part of the Canadian total diet study (TDS) program, we have been analysing food samples for BPA since 2008. In this study, results of BPA in samples of different composite canned foods from 2008-2020 TDS were reported. Clear temporal trends were observed for canned fish and soups, with BPA levels being significantly reduced since 2014 for canned fish products and 2017 for canned soups. Temporal trends were not observed for canned evaporated milk, luncheon meats, and vegetables, with even the highest levels of BPA being detected in recent samples for evaporated milk (57 ng/g), luncheon meats (56 ng/g), and baked beans (103 ng/g). This seems to indicate that BPA-based epoxy resins are still being used in the internal coatings for these canned foods products. Thus, analysis of canned food samples for BPA should be continued for exposure assessment.

Chondrosarcomas are a diverse group of malignant cartilaginous matrix-producing neoplasms. Conventional chondrosarcomas are a continuum of disease based on the biologic activity of the tumor. The tumors range from the relatively biologically benign low-grade tumors or intermediate atypical cartilaginous tumors (ACTs), to malignant, aggressive high-grade tumors. The clinical presentation, radiographic and pathologic findings, treatments and outcomes vary significantly based on the histologic grade of the tumor. Chondrosarcomas present a diagnostic dilemma, particularly in the differentiation between high- and intermediate-grade tumors and that of low-grade tumors from benign enchondromas. A multidisciplinary team at a tertiary sarcoma centre allows for optimal care of these patients.

Cardiovascular manifestations are common (35-100%) in the multisystem inflammatory syndrome in children. Our study aimed to analyze treatment impact and cardiovascular involvement in patients with multisystem inflammatory syndrome in children. The retrospective cohort included 81 patients treated between April 2020 and December 2021 (9.3±4.6 years). Elevated cardiac troponin I and pro-B-type natriuretic peptide were observed in 34.2% and 88.5% of patients, respectively. Myocardial dysfunction was observed in 50.6%. Children older than 10 years had a 4-fold increased risk of myocardial dysfunction (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.4-8.9; p=0.006). A moderate negative correlation was proved between left ventricle ejection fraction and C-reactive protein (rr = - 0.48; p < 0.001). More than one-fifth of the patients presented with shock. Coronary artery dilatation was observed in 6.2% of patients. Mild pericardial effusion was detected in 27.1% of children. On standard electrocardiogram, 52.6% of children had negative T waves in the inferior and/or precordial leads; transient QTc prolongation was registered in 43% of patients. Treatment failure was observed in 19 patients. Patients initially treated with intravenous immunoglobulins had 10-fold higher chances for treatment failure than patients treated with corticosteroids (OR 10.6, 95% CI 3,18 - 35.35; p < 0.001). Cardiovascular manifestations were observed in more than half of the patients, with acute myocardial dysfunction being the most common, especially in children older than 10 years. We established a negative association between the degree of elevation of inflammatory markers and left ventricular ejection fraction. Patients treated with intravenous immunoglobulins who had cardiovascular manifestations had treatment failures more frequently than patients treated with corticosteroids.

Objectives: (1) To develop reference values for health-related fitness in European children and adolescents aged 6-18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries., Methods: This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test-retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method., Results: A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu)., Conclusion: This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coronavirus Disease 2019 (COVID-19) has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 single nucleotide polymorphisms (SNPs), namely rs12980275, rs8099917, rs12979860, and rs368234815. 21.9% and 65.0% of hospitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased Charlson Comorbidity Index (CCI), N/L, and lactate dehydrogenase (LDH) level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19., (© 2023 Wiley Periodicals LLC.)

Introduction: Necrotizing crescentic glomerulonephritis is a major contributor to morbidity and mortality in Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Because therapy relies on immunosuppressive agents with potentially severe adverse effects, a reliable noninvasive biomarker of disease activity is needed to guide treatment., Methods: We used flow cytometry to quantify T cell subsets in blood and urine samples from 95 patients with AAV and 8 controls to evaluate their biomarker characteristics. These were compared to soluble markers, monocyte chemoattractant protein-1 (MCP-1), soluble CD163 (sCD163), soluble CD25 (sCD25), and complement C5a (C5a), measured using multiplex analysis. Available kidney biopsies ( n  = 21) were classified according to Berden., Results: Patients with active renal AAV (rAAV) showed significantly higher urinary cell counts than those in remission, or those with extrarenal manifestation, or healthy controls. Urinary T cells showed robust discrimination of disease activity with superior performance compared to MCP-1 and sCD163. Patients whose kidney biopsies had been classified as "crescentic" according to Berden classification showed higher urinary T cell counts. Discordant regulatory T cells (T reg ) proportions and CD4 + /CD8 + ratio in blood and urine suggested that urinary cells reflect tissue migration rather than mere micro-bleeding. Furthermore, urinary T reg and T helper cells (T H 17) patterns were associated with clinical response and risk of renal relapse., Conclusion: Urinary T cells reflect the renal inflammatory milieu in AAV and provide further insights into the pathogenesis of this chronic condition. Their promising potential as noninvasive diagnostic and prognostic biomarkers deserves further exploitation., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries., Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years., Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world's population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world's population live in countries where PA promotion capacity should be significantly improved., Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion.

Introduction: Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB., Methods and Analysis: A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane's RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health's tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used., Ethics and Dissemination: No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance., Systematic Review Registration: CRD42021282874., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In our previous study, bisphenol S (BPS) was detected unexpectedly and at high levels in meat samples from 2016 and 2020 Canadian total diet study (TDS). In this study, samples of meat and meat products from 2008-2015 and 2017-2019 TDS were also analysed to investigate the consistency of BPS occurrence in meat and identify possible trends and provide some information on the potential sources for BPS in meat. BPS was detected again with the highest levels observed in samples of fresh pork (105 ng/g) and veal cutlets (140 ng/g) from the 2008 TDS. This indicates that the occurrence of BPS in meat is not a recent phenomenon but rather an existing one since 2008 or even earlier. BPS concentrations in meat samples from the 2008 to 2020 TDS varied significantly, e.g. 1.2-118 ng/g in roast beef, 1.8-140 ng/g in veal cutlets, but no trend was observed. The lack of trend for BPS over the period of 13 years (2008-2020) does not support the speculation that BPS is being used to replace BPA in food packaging, and sources other than food packaging may be possible and should be investigated for BPS.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumour-like fibro-osseous lesion in the neuraxis including the spine. It is diagnosed by the presence of the following histological features: granular amorphous to chondromyxoid fibrillary cores with calcification/ossification, peripheral palisading of spindle to epithelioid cells, variable fibrous stroma, and foreign body reaction with multinucleated giant cells, as well as positive NF-L immunostaining. Spinal CAPNON is sometimes named as tumoural calcinosis that is tumour-like dystrophic calcification usually in the periarticular tissue and also described in calcified synovial cyst (CSC). We examined clinical, radiological and pathological features of five spinal CAPNONs and 21 spinal CSCs including three recurrent lesions. The results demonstrated some radiological and pathological overlaps between these two entities, as well as distinct features of each entity to be diagnosed. All CAPNONs showed the diagnostic histological features with NF-L positivity mainly in lesion cores and variable CD8+ T-cells. In contrast, CSCs exhibited the synovial lining and variable degenerative/reactive changes with some CAPNON-like features, but mostly no to occasionally limited NF-L positivity and less CD8+ T-cells with statistically significant differences between groups of CAPNONs and CSCs. Four CSCs contained CAPNON-like foci with the CAPNON diagnostic features including prominent NF-L positivity, and some transitional features from CSC to CAPNON. As the pathogenesis of CAPNON is likely reactive/degenerative in association with an inflammatory/immunological process involving NF-L protein deposition, our findings suggest the link between spinal CAPNON and CSC, with possible transition from CSC to CAPNON or CAPNON developing in reaction to CSC., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The aim of this cross-sectional study was to determine the differences in the morphological characteristics and situational precision among younger and older groups of handball players. The sample of participants consisted of 30 handball players, members of the younger category of the Al-Ahli handball club (Bahrein), divided into two groups: older (U16, n = 18) and younger (U15, n = 12). To evaluate their morphological characteristics, eight variables were measured, while two standardized tests were used to evaluate their situational precision. The results indicate that a statistically significant difference between the groups was noticeable for nine variables in total, seven in morphology (body height, p = 0.010; body mass index, p = 0.049; arm length, p = 0.009; upper arm length, p = 0.016; lower arm length, p = 0.040; the planimetric parameter of the hand, p = 0.005; hand length p = 0.004) and two in situational precision (the standing shot, p = 0.003; the jump shot, p = 0.17), and that the achieved difference ranges from a medium to a large effect. For only one variable (body mass, p = 0.734), significant difference was not determined between the groups. It was also determined (by Cohen's criterion) that handball players with higher longitudinal dimensionality achieve better results for specific precision. Therefore, when selecting young handball players, the aforementioned dimensions should be taken into consideration as predictors of success.

The aim of the study was to examine the immunomodulatory effect of crude Chelidonium majus L ethanolic extract on ex vivo harvested peripheral blood mononuclear cells (PBMNCs). PBMNCs were isolated by density gradient centrifugation. The PBMNC cytotoxicity assay was performed with HeLa tumor cells as target cells. MTT assay was used to estimate the proliferation effect of extract and cytotoxic efficiency of treated PBMNCs. Flow cytometric analysis was used for immunophenotyping. Treatment induced moderate proliferative response, perturbation in PBMNC ratios, and the emergence of some unconventional subpopulations. The percentage ratio of double positive CD4+ and CD8+ T lymphocytes and monocytes, ratio of T and B lymphocytes expressing CD14, and percentage of NK cells expressing CD57 increased after treatment, indicating activation of PBMNC subpopulations. Cytotoxic activity against HeLa cells was enhanced. Activation of PBMNCs and enhancement of their cytotoxic effect toward HeLa cells indicate the immunostimulatory effect of Ch. majus ethanolic extract.

The aim of this study was to identify some of the secondary metabolites present in acetonic, methanolic, and hexanic extracts of lichen Xanthoparmelia stenophylla and to examine their antioxidant, antimicrobial, and cytotoxic activity. Compounds of the depsid structure of lecanoric acid, obtusic acid, and atranorin as well as usnic acid with a dibenzofuran structure were identified in the extracts by HPLC. The acetone extract was shown to have the highest total phenolic (167.03 ± 1.12 mg GAE/g) and total flavonoid content (178.84 ± 0.93 mg QE/g) as well as the best antioxidant activity (DPPH IC50 = 81.22 ± 0.54). However, the antimicrobial and antibiofilm tests showed the best activity of hexanic extract, especially against strains of B. cereus, B. subtilis, and S. aureus (MIC < 0.08, and 0.3125 mg/mL, respectively). Additionally, by using the MTT method, the acetonic extract was reported to exhibit a strong cytotoxic effect on the HeLa and HCT-116 cell lines, especially after 72 h (IC50 = 21.17 ± 1.85 and IC50 = 21.48 ± 3.55, respectively). The promising antioxidant, antimicrobial, and cytotoxic effects of Xanthoparmelia stenophylla extracts shown in the current study should be further investigated in vivo and under clinical conditions.

In this study, the occurrence of bisphenol S (BPS) in the meat and meat products from a recent Canadian Total Diet Study (TDS) was investigated in more detail. In addition to their composite samples, the individual raw meat and meat products were also analysed for BPS to investigate the variations of BPS levels and provide some information on the potential sources for BPS in meat. BPS was detected in all the 11 composite samples of different meat and meat products, with the highest level in roast beef (118.23 ng/g) and lowest in cured pork (0.14 ng/g) and cold cuts luncheon meats (0.18 ng/g). BPS was also detected in all the 84 individual raw meat and meat products, with the highest level of 257.61 ng/g in roast beef, followed by 190.41 ng/g in organ meats, 110.15 ng/g in beef steak, 27.91 ng/g in veal cutlets, 17.63 ng/g in wieners & sausages, and 15.27 ng/g in ground beef. However, significant variations of BPS levels were observed in the individual meat and meat product samples under the same category collected from different stores. This may indicate that packaging is unlikely the sources for BPS in meat otherwise BPS levels would have been more or less the same with the same type of packaging (Styrofoam and cling film) regardless where they were collected. Thus, sources other than food packaging, such as the contaminated feed and farming environment (e.g. grass) for animals (e.g. cow), may be possible and should be investigated in future studies.

Competing Interests: Competing interests: The authors declare no conflict of Interest.

This narrative review of the literature assessed whether regular physical exercise and sleep patterns, fasting and autophagy, altogether can be an adequate strategy for achieving healthy longevity and well-being within different stage of life. There are a large number of studies dealing with well-being and healthy longevity; however, few of them have given us a specific formula for how to live long and healthy. Despite all the advances that have been made to create adequate physical exercise programs, sleep patterns or nutritional protocols, the relation between different types of fasting, nutritional supplementation as well as regular physical exercise and sleep patterns have not yet been satisfactorily resolved to cause the best effects of autophagy and, therefore, well-being and healthy longevity. In this way, future studies should clarify more efficiently the relationship between these variables to understand the association between regular physical exercise, sleep patterns, fasting and autophagy for healthy longevity and well-being., 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., (Copyright © 2021 Min, Masanovic, Bu, Matic, Vasiljevic, Vukotic, Li, Vukovic, Fu, Jabucanin, Bujkovic and Popovic.)

Background: In multisystem inflammatory syndrome in children (MIS-C) temporarily associated with coronavirus disease-19 (COVID-19), myocardial damage has been reported., Materials and Methods: A retrospective observational cohort study included children under 18 who had a myocardial injury related to COVID-19 treated in mother and child health institute from April 2020 to August 2020. Myocardial injury related to COVID-19 was manifested by elevated serum cardiac troponin and NT-proBNP with LV dysfunction, arrhythmias, and coronary arteries (CAs) dilatation or aneurysms. During the short-term follow-up, cardiac testing (electrocardiography, laboratory analysis, echocardiography, 24-h Holter monitoring, exercise stress test, and cardiac magnetic resonance) was performed., Results: Six male adolescents (14.7 ± 2.4 years) were included in the analysis (2/6 had MIS-C shock syndrome). All patients had elevated acute-phase reactants and NT-proBNP, whereas troponins were elevated in 5/6 patients. Echocardiography revealed left ventricular (LV) systolic dysfunction (EF 45.2 ± 6.9%); 2/6 had dilated CAs. IVIG was prescribed to all patients with MIS-C. Four patients required inotropic drug support. During hospitalization, a significant reduction of CRP, LDH, NT-proBNP, and D-dimer ( P < 0.05) was registered. LV systolic function recovery was registered 3 days after applied therapy ( P < 0.001). None of the patients developed dilated cardiomyopathy or CA aneurysms., Conclusions: With early recognition and adequate MIS-C therapy, children recovered entirely, maintained in the short-term follow-up period., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

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.

Background: Cardiovascular complications with myocarditis in multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 infection have been reported, but the optimal therapeutic strategy remains unknown., Methods: A retrospective cohort study included 19 patients with acute left ventricular systolic dysfunction associated with MIS-C, average years of age 13.2 ± 3.8, treated from April 2020 to April 2021., Results: Treatment failure (TF) was observed in 8 patients (in the intravenous immunoglobulin [IVIG] group 7/10; in the corticosteroid [CS] group 1/9). The independent risk factor for TF was IVIG treatment (odds ratio [OR] 18.6, 95% confidence interval [CI] 1.6-222.93, P = 0.02). Patients initially treated with CS became afebrile during in-hospital day 1 (1.5, interquartile range [IQR] 1-2), while IVIG-treated patients became afebrile on in-hospital day 4 (IQR 2-4.25), after CS was added. The C-reactive protein (CRP) significantly declined in CS-treated patients on day 2 (P = 0.01), while in the IVIG group, CRP decreased significantly on the fourth day (P = 0.04). Sodium and albumin levels were higher on third in-hospital day in the CS group than in the IVIG group (P = 0.015, P = 0.03). A significant improvement and normalization of ejection fraction (EF) during the first 3 days was observed only in the CS group (P = 0.005). ICU stays were shorter in the CS group (4, IQR 2-5.5) than in the IVIG group (IVIG group 7, IQR 6-8.5) (P = 0.002)., Conclusions: Among children with MIS-C with cardiovascular involvement, treatment with CS was associated with faster normalization of LV EF, fever, laboratory analysis, and shorter ICU than IVIG-treated patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the influence of Nordic walking (NW) on hip joint loads in order to determine whether it can be safely performed during postoperative physiotherapy in patients after orthopeadic surgery of the hip., Methods: Internal hip joint loads were directly measured in vivo in 6 patients using instrumented hip prostheses during NW and ordinary walking (OW). All patients received training in two different NW techniques (double-poling and the diagonal technique) by a certified NW instructor. Measurements were conducted on a treadmill at a speed of 4 km/h on level ground, at 10% inclination and at 10% slope as well as on a level lawn at a self chosen comfortable speed. Resultant contact force (F res ), bending moment (M bend ) and torsional torque (M tors ) were compared between NW and OW as well as between both NW techniques., Results: Joint loads showed a double peak pattern during all setups. Neither NW technique significantly influenced hip joint loads at the time of the first load peak during contralateral toe-off (CTO), which was also the absolute load peak, in comparison to OW. Compared to OW, double-poling significantly reduced F res and M bend at the time of the second load peak during the contralateral heel strike (CHS) on level ground both on the treadmill (- 6% and - 7%, respectively) and on the lawn (- 7% and - 9%). At 10% inclination, the diagonal technique increased F res and M bend at CHS (by + 6% and + 7%), but did not increase the absolute load peak at CTO., Conclusion: Joint loads during NW are comparable to those of OW. Therefore, NW can be considered a low-impact activity and seems to be safe for patients that are allowed full weight bearing, e.g. during postoperative rehabilitation after THA., (© 2021. The Author(s).)