Abstract Orbital metastatic lesions are rare entities1-3 best treated with radical surgical resection with preservation/improvement of neurological and visual function.1-9 Renal cell metastases, in particular, respond less favorably to radiation.9 To our knowledge, an operative video of microsurgical resection of a renal cell carcinoma metastasis to the superior orbital fissure and orbit has not been reported. A patient presented with worsening right eye vision as demonstrated on preoperative visual field testing and found to have a 3 × 1 × 1 cm lesion in the orbit and superior orbital fissure. The patient was placed supine and stealth neuronavigation was used to aid in tumor localization and extension. A cranio-orbital craniotomy and pretemporal exposure2,10,11 were performed to allow extradural dissection of the dura propria off the lateral wall of the cavernous sinus. Right-sided extradural cranial nerves II, III, IV, V1, and V2 were identified, and a high-speed diamond drill was used to perform extradural anterior clinoidectomy and optic nerve decompression. Microsurgical resection of the intraorbital tumor components was performed by the senior author (KIA) to delineate the plane between tumor and periorbita. An oval-shaped dural opening was made to resect the dura involved by tumor, confirmed on histological analysis, followed by closure via dural allograft. The patient's right-sided visual field improved markedly after surgery. Metastatic renal cell carcinoma of the orbit should be resected while preserving and improving preoperative neurological and visual function. The orbitocranial pretemporal approach offers wide visualization to achieve surgical resection. The patient provided written consent and permission to publish her image.

Abstract Rationale: Pheochromocytoma (PHEO) is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. Most pediatric PHEOs are functional tumors, and clinical manifestations are related to catecholamine hypersecretion and/or tumor mass effects. Patient concerns: We report here a case of a 10-year-old boy with a highly functional adrenal PHEO detected after the evaluation of a generalized tonic-clonic seizure in the patient. His vital signs at admission were: blood pressure up to 220/135 mm Hg; pulse, 112 beats/min; temperature, 37.4°C; respiratory rate, 22 breaths/min. Diagnosis: A 24-hour urine collection for catecholamines test showed a marked increase in Vanillylmandelic acid levels (338.9 μmol/L). An abdominal magnetic resonance imaging revealed a well-defined left adrenal gland mass measuring ∼5 cm in its largest dimension. Interventions: The mass was surgically removed, and histopathological examination revealed PHEO with low malignant potential (Adrenal Gland Scaled Score/PASS/ < 4). Outcomes: The patient was discharged on the 10th postoperative day in good condition. At 24-month follow-up, the patient was doing well without complications such as tumor recurrence, elevated blood pressure, and seizure. Lessons: PHEO should be considered in the differential diagnosis of children with seizures presenting in the emergency department. A multidisciplinary approach to the evaluation and treatment of PHEO is also crucial for a successful outcome.

Children’s health behaviors are highly influenced by their parents and family. This study aimed to prospectively evaluate the parental/familial factors associated with physical activity levels (PALs) among older adolescents. The participants were 766 adolescents, who were prospectively observed at baseline (when they were 16 years of age), at first follow-up measurement (FU1; 17 years of age), and second follow-up measurement (FU2; 18 years of age). Sociodemographic factors (age, gender, socioeconomic status, and sport participation) and parental/familial variables were evaluated at baseline. PALs (evidenced by the Physical-Activity Questionnaire-for-Adolescents) were prospectively evidenced at baseline, FU1, and FU2. Factorial analysis of variance for repeated measurements showed a significant decrease in PALs during the study course (F = 83.05, p < 0.001). Sport participation and male gender were significant predictors of PALs at baseline, FU1, and FU2. Logistic regression, controlled for sport participation and male gender, evidenced paternal education as a significant predictor of baseline PALs. Parental conflict was a significant predictor of PALs in all three testing waves. The significant influence of paternal education on the children’s PALs existed from younger adolescence until the age of 17 years. The association between parental conflict and PALs developed in older adolescence. These results should be used in the development of specific and targeted interventions aimed at the improvement of PALs and a reduction of sedentarism in youth.

Asphalt production plants play an important role in the field of civil engineering, but also in the entire economic system since the construction of roads enables uninterrupted functioning within it. In this paper, the ranking of asphalt production plants on the territory of the Autonomous Province of Vojvodina has been performed. The modern economy needs contemporary models and methods to solve complicated MCDM problems and, for these purposes, it has been developed an original Interval Rough Number (IRN) Multi-criteria decision-making (MCDM) model that implies an extension of two methods belonging to the field with interval rough numbers. After forming a list of eight most significant criteria for assessing the efficiency of asphalt production plants, the Interval Rough Number PIvot Pairwise RElative Criteria Importance Assessment (IRN PIPRECIA) method was developed to determine the significance of the criteria. A total of 21 locations with asphalt mixture installation were considered. For that purpose, seven asphalt production plants were included, and for their ranking, the IRN EDAS (Evaluation based on Distance from Average Solution) method was created. The aim of this paper is to develop a novel interval rough model that can be useful for determining the efficiency of asphalt production plants. Averaging in group decision-making (GDM) for both methods was performed using an IRN Dombi weighted geometric averaging (IRNDWGA) aggregator. The obtained results show that (A15) Ruma (SP)–Mačvanska Mitrovica–Zasavica has the best characteristics out of the set of locations considered in this study. However, Alternatives A6 and A19 are also variants with remarkably good characteristics since there is very little difference in values compared to the first-ranked alternative. Also, the obtained results have shown that the developed model is applicable, which is proven through a comparative analysis.

Harnessing renewable energy sources (RES) using hybrid systems for buildings is almost a deontological obligation for engineers and researchers in the energy field, and increasing the percentage of renewables within the energy mix represents an important target. In crowded urban areas, on-site energy production and storage from renewables can be a real challenge from a technical point of view. The main objectives of this paper are quantification of the impact of the consumer’s profile on overall energy efficiency for on-site storage and final use of solar thermal energy, as well as developing a multicriteria assessment in order to provide a methodology for selection in prioritizing investments. Buildings with various consumption profiles lead to achieving different values of performance indicators in similar configurations of storage and energy supply. In this regard, an analysis of the consumption profile’s impact on overall energy efficiency, achieved in the case of on-site generation and storage of solar thermal energy, was performed. The obtained results validate the following conclusion: On-site integration of solar systems allowed the consumers to use RES at the desired coverage rates, while restricted by on-site available mounting areas for solar fields and thermal storage, under conditions of high energy efficiencies. In order to segregate the results and support optimal selection, a multicriteria analysis was carried out, having as the main criteria the energy efficiency indicators achieved by hybrid heating systems.

This study aims to do a morphological and biochemical characterization of selected wild hop populations from the Banja Luka region, as plant material with potential value for introduction into plant selection. Female inflorescences (cones) from seven populations (DKH3, DKH5, DKH6, DKH8, DKH9, DKH10, and DKH11) were sampled in 2018 and 2019. Hop cones were collected in October 2018 and 2019 for morphological characterization, when 50 cones per population were analyzed, and also the cones were collected in mid-September in 2019 for biochemical characterization. Morphological parameters were carried out for: cone length (cm), number of nodes per cone spindle, cone density, and number of seeds per cone, all important agronomic characters in hop production. Also, 27 components of essential oil and 6 components of hop resins were analyzed. Statistical analysis of morphological characteristics was performed by factorial analysis of variance (year × population), and the significance of individual differences was determined by LSD test. The grouping of examined hop populations according to the manifested morphological characteristics was performed by cluster analysis. Statistical analysis for biochemical characteristics was performed by analysis of variance, and the significance of the differences was tested by Tukey’s statistical test. In order to determine similarities between different population multivariant statistical method Principal component analysis (PCA) was applied. According to morphological and biochemical analysis, DKH6 hop population is singled out as the most valuable for hop breeding.

BACKGROUND Genome-wide DNA methylation profiling has recently been developed into a tool that allows tumor classification in central nervous system tumors. Extracellular vesicles (EVs) are released by tumor cells and contain high molecular weight DNA, rendering EVs a potential biomarker source to identify tumor subgroups, stratify patients and monitor therapy by liquid biopsy. We investigated whether the DNA in glioblastoma cell-derived EVs reflects genome-wide tumor methylation and mutational profiles and allows non-invasive tumor subtype classification. METHODS DNA was isolated from EVs secreted by glioblastoma cells as well as from matching cultured cells and tumors. EV-DNA was localized and quantified by direct stochastic optical reconstruction microscopy. Methylation and copy number profiling was performed using 850k arrays. Mutations were identified by targeted gene panel sequencing. Proteins were differentially quantified by mass spectrometric proteomics. RESULTS Genome-wide methylation profiling of glioblastoma-derived EVs correctly identified the methylation class of the parental cells and original tumors, including the MGMT promoter methylation status. Tumor-specific mutations and copy number variations (CNV) were detected in EV-DNA with high accuracy. Different EV isolation techniques did not affect the methylation profiling and CNV results. DNA was present inside EVs and on the EV surface. Proteome analysis did not allow specific tumor identification or classification but identified tumor-associated proteins that could potentially be useful for enriching tumor-derived circulating EVs from biofluids. CONCLUSIONS This study provides proof of principle that EV-DNA reflects the genome-wide methylation, CNV and mutational status of glioblastoma cells and enables their molecular classification.

This study investigated the correlation between bone characteristics, the design of orthodontic mini-implants, the pull-out force, and primary stability. This experimental in vitro study has examined commercial orthodontic mini-implants of different sizes and designs, produced by two manufacturers: Tomas-pin SD (Dentaurum, Ispringen, Germany) and Perfect Anchor (Hubit, Seoul, Korea). The total number of 40 mini-implants were tested. There are two properties that are common to all tested implants—one is the material of which they are made (titanium alloy Ti-6Al-4V), and the other is the method of their insertion. The main difference between the mini-implants, which is why they have been selected as the subject of research in the first place, is reflected in their geometry or design. Regardless of the type of implant, the average pull-out forces were found to be higher for a cortical bone thickness (CBTC) of 0.62–0.67 mm on average, compared to the CBTC < 0.62 mm, where the measured force averages were found to be lower. The analysis of variance tested the impact of the mini-implant geometry on the pull-out force and proved that there is a statistically significant impact (p < 0.015) of all three analyzed geometric factors on the pull-out force of the implant. The design of the mini-implant affects its primary stability. The design of the mini-implant affects the pulling force. The bone quality at the implant insertion point is important for primary stability; thus, the increase in the cortical bone thickness increases the value of the pulling force significantly.

OBJECTIVE Tumors of the brain and spine make up about 20% of all childhood cancers; they are the second most common form of childhood cancer after leukemia. Brain tumors are the most common solid tumor in children. Symptoms depend on a variety of factors, including location of the tumor, age of child, and rate of tumor growth. The aim of study was to present our experience with the diagnosis and treatment of brain tumors in children. PATIENTS AND METHODS The aim of this study is to analyze clinicopathological characteristics, treatments, complications, and outcomes in children with brain tumors. This study is a retrospective analysis of 27 consecutive patients younger than 16 years and hospitalized for surgical treatment of brain tumors. Intracranial hypertension, neurological status, radiological computerized tomography (CT) or magnetic resonance imaging (MRI) findings, tumor localization, type of resection, hydrocephalus treatment, histopathology, complications, and outcome were analyzed. RESULTS Twenty-seven surgeries were performed in patients for brain tumors. There were 9 females and 18 males. The average patient age was 7.8 years. There were 11 (40%) children with astrocytoma; of these, there were 9 (82%) pilocytic astrocytomas and 2 (18%) ordinary histopathological subtypes of high-grade tumors. CONCLUSION As with any cancer, prognosis and long-term survival vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with a brain tumor.

Amazonian wildfires in 2019 have raised awareness about rainforest burning due to increased emissions of particulate matter and carbon. In the context of these emissions, by-products of lignin thermal degradation (i.e. methoxyphenols) are often neglected. Methoxyphenols entering the atmosphere may form intermediates with currently unknown reaction mechanisms and toxicity. This study for the first time provides a comprehensive insight into the impact of lignin degradation products [guaiacol, catechol], and their nitrated intermediates [4-nitrocatechol, 4,6-dinitroguaiacol, 5-nitroguaiacol] on zebrafish Danio rerio. Results revealed 4-nitrocatechol and catechol as the most toxic, followed by 4,6DNG > 5NG > GUA. The whole-organism bioassay integrated with molecular modeling emphasized the potential of methoxyphenols to inhibit tyrosinase, lipoxygenase, and carbonic anhydrase, consequently altering embryonic development (i.e. affected sensorial, skeletal, and physiological parameters, pigmentation formation failure, and non-hatching of larvae). The whole-organism bioassay integrated with in silico approach confirmed the harmful effects of lignin degradation products and their intermediates on aquatic organisms, emphasizing the need for their evaluation within ecotoxicity studies focused on aquatic compartments.

A mechanistic understanding of the regulatory circuits that control the effector responses of memory T helper lymphocytes, and in particular their ability to produce pro‐inflammatory cytokines, may lead to effective therapeutic interventions in all immune‐related diseases. Activation of T lymphocytes induces robust immune responses that in most cases lead to the complete eradication of invading pathogens or tumor cells. At the same time, however, such responses must be both highly controlled in magnitude and limited in time to avoid unnecessary damage. To achieve such sophisticated level of control, T lymphocytes have at their disposal an array of transcriptional and post‐transcriptional regulatory mechanisms that ensure the acquisition of a phenotype that is tailored to the incoming stimulus while restraining unwarranted activation, eventually leading to the resolution of the inflammatory response. Here, we will discuss some of these cell‐intrinsic mechanisms that control T cell responses and involve transcription factors, microRNAs, and RNA‐binding proteins. We will also explore how the same mechanisms can be involved both in anti‐tumor responses and in autoimmunity.

OBJECTIVE Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. APPROACH AND RESULTS Using human coronary artery smooth muscle cells we found that the transcriptional co-activator MRTFA promotes lipid accumulation via several mechanisms, including direct transcriptional control of LDL receptor, enhanced fluid-phase pinocytosis and reduced lipid efflux. Inhibition of MRTF activity with CCG1423 and CCG203971 significantly reduced lipid accumulation. Furthermore, we demonstrate enhanced MRTFA expression in vascular remodeling of human vessels. CONCLUSIONS This study demonstrates a novel role for MRTFA as an important regulator of lipid homeostasis in vascular smooth muscle cells. Thus, MRTFA could potentially be a new therapeutic target for inhibition of vascular lipid accumulation.

Sport is one of the world’s most important resources and an indispensable part of international culture. Men and women participate in most sports from football, basketball, boxing to extreme sports. The aim of this paper is to research gender equality in many aspects of sport, from equal pay, sponsorship agreements, to scholarships as state support to talented athletes. The paper presents a theoretical framework for defining sport and its significance. The media attitude towards sports is discussed and the symbiosis relationship between sports and the media is emphasized. The focus of the paper is on women in sports and their progress towards gender equality in all sports activities from participation, coaching positions to management. An analysis of the results of the survey was done. The survey was conducted on a representative sample of 201 respondents. The questionnaire was on sports monitoring and key issues on equality in the choice of sports, media attention, equal pay and sponsorship agreements as well as on prejudice against female athletes and career duration and monitoring of women’s football given the growing popularity of the sport.

Perennial plant Mentha pulegium L. (pennyroyal, Lamiaceae) can be found in Europe and Mediterranean. In areas where it thrives, M. pulegium is used in nutrition and as medicinal plant. Essential oil of M. pulegium is also a frequent constituent of foods and fragrances, because of mint‐like odor. Regarding the use of M. pulegium in traditional medicine and nutrition, as well as fact that essential oils are potential sources of bioactive components, this study was conducted to examine the chemical composition of essential oil of M. pulegium wild growing in Bosnia and Herzegovina and its biological activity. The chemical profile testing was made using GC/MS and GC/FID technique. Potential of cholinesterase inhibition was tested by Ellman's assay. The antioxidant activity was tested by DPPH and FRAP assay. The dominant components in analyzed oil were pulegone 54.4 %, p‐menthone 14.0 % and piperitenone 12.8 %. Good antioxidant activity and moderate cholinesterase inhibition potential of tested essential oil indicates to possibility of its use in treatment of diseases related to free radicals, Alzheimer disease and as lipid protecting antioxidant.