Search

Kirurška odstranitev zob je najpogostejši kirurški poseg pri osebah s prirojeno motnjo strjevanja krvi (MSK). Da se čezmerna krvavitev med posegom in po njem prepreči, se pri osebah z MSK, tudi pri lahkih oblikah bolezni, poseg načrtuje z medsebojnim sodelovanjem maksilofacialnega ali oralnega kirurga in hematologa. Prav krvavitev po ekstrakciji zoba je lahko tudi prvi znak lahke oblike še neprepoznane prirojene MSK, ko kirurg bolnika po opravljenem posegu zaradi čezmerne krvavitve napoti k hematologu za diagnosticiranje in zdravljenje.

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS)  5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development.

Prader-Willi syndrome (PWS) is a complex genomic imprinting disorder of chromosomal region 15q, characterized by hypotonia, feeding problems, and emotional-behavioural problems. Comprehensive treatment includes pharmacological therapy with the replacement of growth hormone as well as other pharmacological therapies against, e.g., depression, attention disorders, and psychosis. In addition, non-pharmacological measures and behavioural strategies are the keys to caring for these patients. We present a comprehensive treatment of children with Prader-Willi syndrome as implemented at our Centre for Education, rehabilitation, and Training CIRIUS Kamnik. We present a cohort of children with genetically confirmed PWS (n=5; age=11.4 ± 3.1 years, of which four were boys) and comprehensive follow-up we offer with dietary counselling, body content measurement (with electronic device BIVA), physiatry treatment with the prescription of medical devices and psychological treatment, all of which contribute to their better functionality and control of the condition. The paper also presents practical instructions on how to act in specific behavioural situations, using examples.

Sindrom Prader-Willi (PWS) je kompleksna genetska motnja, ki je posledica pomanjkljivega izražanja genov na kromosomski regiji 15q, za katero so značilne hipotonija, težave s hranjenjem in čustveno-vedenjske težave. Celostna obravnava vključuje somatsko zdravljenje z nadomeščanjem rastnega hormona kot tudi z drugim medikamentnim zdravljenjem npr. zdravljenje depresije, motnje pozornosti, psihoze. Poleg tega pa so ključnega pomena nemedikamentni ukrepi: dietetična in fiziatrična obravnava ter opremljenost z medicinskimi pripomočki in vedenjske strategije. V prispevku prikazujemo celostno obravnavo otrok s sindromom Prader-Willi, kot se izvaja v Centru za izobraževanje, rehabilitacijo in usposabljanje CIRIUS Kamnik od vstopa v šolo do končanega šolanja oziroma do dopolnjenega 26. leta starosti. Predstavimo kohorto otrok z genetsko potrjenim PWS (starost 11.4 ± 3.1 let, od tega 4 fantje in 1 dekle) in način zdravstvene obravnave v naši ustanovi s spremljanjem pri dietetiku, merjenjem telesne sestave (z elektronskim analizatorjem BIVA) in z individualnimi prehranskimi ukrepi, s fiziatrično obravnavo s predpisovanjemm medicinskih pripomočkov in psihološko obravnavo, kar vse prispeva k njihovi boljši funkcionalnosti in obvladovanju stanja. Na prikazu primerov so predstavljeni tudi praktični napotki, kako ravnati v specifičnih vedenjskih situacijah.

Objectives: To determine secular trends in body height, fat-mass, fat-free mass, and external skeletal robustness in young adults and examine possible relationship between them. Methods: Anthropometric data (body height, body mass; skinfold thickness (SFT) – triceps, abdominal, thigh; circumferences (C) – waist, upper arm, thigh; width – elbow, knee) of young adults aged 20-25 years (N = 5303; males 1985, females 3318) were used from the Slovenian (data)Base of Anthropometric Measurements from 1960 to 2023. Multiple linear regressions were performed. Results: The most significant positive secular trends (p < 0.000) were observed in males for abdominal SFT (B = 0.151, R2 = 0.169) and thigh SFT (B = 0.131, R2 = 0.142). In females, similar trend was observed in waist C (B = 0.151; R2 = 0.169). The most significant negative secular trend (p < 0.001) was observed in muscle area of lower limbs in both sexes (males: B = - 0.427, R2 = 0.000; females: B = - 0.875, R2 = 0.300). Body height and overall body mass were the most important factors influencing the observed decline in external skeletal robustness assessed with frame index according to elbow and knee width according to multiple linear regression. Conclusion: Over the last 60 years, a positive secular trend was observed in body height and body fat, while a negative trend was noted in muscle mass. Increases in body height and overall body mass had the most significant impact on the observed decrease in assessed external skeletal robustness over time.

IntroductionColorectal cancer (CRC) ranks as the third most prevalent malignancy globally, with a concerning rise in incidence among young adults. Despite progress in understanding genetic predispositions and lifestyle risk factors, the intricate molecular mechanisms of CRC demand exploration. MicroRNAs (miRNAs) emerge as key regulators of gene expression and their deregulation in tumor cells play pivotal roles in cancer progression.MethodsNanoString's nCounter technology was utilized to measure the expression of 827 cancer-related miRNAs in tumor tissue and adjacent non-involved normal colon tissue from five patients with locoregional CRC progression. These expression profiles were then compared to those from the primary colon adenocarcinoma (COAD) cohort in The Cancer Genome Atlas (TCGA).Results and discussionIntriguingly, 156 miRNAs showed a contrasting dysregulation pattern in reccurent tumor compared to their expression in the TCGA COAD cohort. This observation implies dynamic alterations in miRNA expression patterns throughout disease progression. Our exploratory study contributes to understanding the regulatory landscape of recurrent CRC, emphasizing the role of miRNAs in disease relapse. Notable findings include the prominence of let-7 miRNA family, dysregulation of key target genes, and dynamic changes in miRNA expression patterns during progression. Univariate Cox proportional hazard models highlighted miRNAs associated with adverse outcomes and potential protective factors. The study underscores the need for more extensive investigations into miRNA dynamics during tumor progression and the value of stage specific biomarkers for prognosis.

To examine the main drivers of firm growth, we estimated a model integrating firm-level, industry-specific as well as country-level determinants, aiming at a comprehensive explanation of firm growth. We used a large dataset of European firms for the 2005–2017 period and combined Amadeus firm-level data with macroeconomic variables and multidimensional measures of institutional framework, based on a range of sources. Using different panel regression model specifications, we found the most consistent relationships for firm-level determinants. Among country-level determinants, infrastructure quality, inward FDI, natural resources, and inequality show a consistently positive and significant relation with firm growth.

Bacterial overgrowth, also known as dysbiosis, is a common concomitant of canine atopic dermatitis. Microbial diversity is decreased and coagulase-positive staphylococci are more abundant in dogs with canine atopic dermatitis compared to healthy dogs. Antimicrobial therapy restores the diversity of the skin microbiome; however, this effect can diminish after treatment is discontinued. Therapies for skin dysbiosis have traditionally included antibiotics and antiseptic medications. Due to increasing microbial resistance to antibiotics, the era of novel antimicrobial agents for the treatment of skin infections has already begun. Recent research highlights potential new treatment options, of which one of the most promising appears to be the use of bacteriophages. Bacteriophages are viruses that can infect and kill bacteria without having negative effects on human or animal cells. This article provides an update on human and veterinary research on phage therapy as a potential approach for the treatment of bacterial infections, with a focus on the treatment of skin dysbiosis in atopic dogs. The clear clinical potential of phage therapy, its advantages and disadvantages, and the legal, biological, technical, and economic challenges it faces for its further implementation and wider application are outlined.

In the search for novel polymeric molecules that could be used as electroactive materials, seven novel polyenaminones were prepared in high yields by the transaminative polymerization of resorcinol-derived bis-enaminones with m- and p-phenylenediamine and with 2,5-diaminohydroquinone. The obtained polymers show very low solubility in organic solvents and absorb UV light and visible light at wavelengths below 500 nm. All the obtained polymeric products were tested for redox activity in a Li battery setup. The 2,5-diaminohydroquinone-derived compound showed the best redox activity, with a maximum capacity of 86 mAh/g and relatively good capacity retention, thus confirming the hydroquinone group as the primary redox-active group. Other potential redox-active groups, such as resorcinol and conjugated carbonyls, showed limited activity, while variations in the phenylene groups and the substitution of phenolic groups in the resorcinol residue did not impact the electrochemical activity of the polymers. Their electrochemical properties, together with their previously established chemical recyclability, make polyenaminones promising scaffolds for the development of materials for sustainable energy storage applications.

IntroductionResidents of long-term care facilities (LTCFs) are at high risk of morbidity and mortality due to COVID-19, especially when new variants of concern (VOC) emerge. To provide intradisciplinary data in order to tailor public health interventions during future epidemics, available epidemiologic and genomic data from Slovenian LTCFs during the initial phases of the COVID-19 pandemic was analyzed.MethodsThe first part of the study included SARS-CoV-2 reverse-transcription Real-Time PCR (rtRT-PCR) positive LTCF residents, from 21 facilities with COVID-19 outbreaks occurring in October 2020. The second part of the study included SARS-CoV-2 rtRT-PCR positive LTCF residents and staff between January and April 2021, when VOC Alpha emerged in Slovenia. Next-generation sequencing (NGS) was used to acquire SARS-CoV-2 genomes, and lineage determination. In-depth phylogenetic and mutational profile analysis were performed and coupled with available field epidemiological data to assess the dynamics of SARS-CoV-2 introduction and transmission.Results370/498 SARS-CoV-2 positive residents as well as 558/699 SARS-CoV-2 positive residents and 301/358 staff were successfully sequenced in the first and second part of the study, respectively. In October 2020, COVID-19 outbreaks in the 21 LTCFs were caused by intra-facility transmission as well as multiple independent SARS-CoV-2 introductions. The Alpha variant was confirmed in the first LTCF resident approximately 1.5 months after the first Alpha case was identified in Slovenia. The data also showed a slower replacement of existing variants by Alpha in residents compared to staff and the general population.DiscussionMultiple SARS CoV-2 introductions as well as intra-facility spreading impacted disease transmission in Slovenian LTCFs. Timely implementation of control measures aimed at limiting new introductions while controlling in-facility transmission are of paramount importance, especially as new VOCs emerge. Sequencing, in conjunction with epidemiological data, can facilitate the determination of the need for future improvements in control measures to protect LTCF residents from COVID-19 or other respiratory infections.

IntroductionAntibiotic resistance represents a growing global threat, and thus the motivation to develop novel and combined methods of bacterial inactivation is increasing. Electroporation is a technique in which electric pulses of sufficient strength are applied to permeabilize cells, including bacteria. Combining antibacterials with electroporation is a promising strategy to potentiate their bactericidal and bacteriostatic effectiveness. This approach has already proved useful for increasing bacterial inactivation, yet most studies so far have mainly focused on the maximal achievable effects, and less on the underlying mechanisms. We recently demonstrated that in the Gram-negative (G–) bacterium Escherichia coli, electroporation potentiates antibacterials targeting the peptidoglycan wall more than those with intracellular targets. However, in Gram-positive (G+) bacteria, the wall is directly accessible from the outside, and thus the dependence of potentiation on the antibacterial’s target may be rather different. Here, we compare the inactivation and growth inhibition of the G+ bacterium Lactiplantibacillus plantarum for two antibiotics with different modes of action: ampicillin (inhibits cell-wall synthesis) and tetracycline (inhibits intracellular protein synthesis).MethodsWe used antibiotic concentrations ranging from 0 to 30 × MIC (minimum inhibitory concentration that we predetermined for each antibiotic), a single 1-ms electric pulse with an amplitude from 0 to 20 kV/cm, and post-pulse pre-dilution incubation of 24 h or 1 h.ResultsElectroporation increased the inhibition and inactivation efficiency of both antibiotics, but this was more pronounced for tetracycline, with statistical significance mostly limited to 24-h incubation. In general, both inhibition and inactivation grew stronger with increasing antibiotic concentration and electric field amplitude.DiscussionOur results indicate that electroporation potentiates inactivation of G+ bacteria to a larger extent for antibiotics that inhibit intracellular processes and require transport into the cytoplasm, and to a smaller extent for antibiotics that inhibit cell-wall synthesis. This is the inverse of the relation observed in G– bacteria, and can be explained by the difference in the envelope structure: in G– bacteria the outer membrane must be breached for wall-inhibiting antibiotics to access their target, whereas in G+ bacteria the wall is inherently accessible from the outside and permeabilization does not affect this access.

With increased interest in materials and construction in the architectural field, the use of building structure as the element of architectural expression has gained interest in recent years. In his analysis of contemporary Swiss architecture, Arthur Rüegg has coined the notion of “Strong Structures” for the tendency to activate a load-bearing structure for spatial and conceptual expression. The article applies this notion to the works of renowned Japanese architect Kazuo Shinohara, who has influenced many prominent Swiss figures in the debate over “Strong Structures.” By conducting phenomenological research on his experimental practices in House in White, Tanikawa House, and House in Uehara, the article examines how Shinohara used the organisation of structural elements and relations to express the architectural and cultural context. Finally, by contrasting the structural design methods used in Switzerland and Japan, this article aims to introduce a relational structure design mindset in order to complement and extend the concept of “Strong Structures”, which can enrich structural design by focusing on the art of structural relations.

Low-grade gliomas (LGG) are the most common primary tumours in the central nervous system in children. Histologically, they are a heterogeneous group of brain tumours. The most common of them is pilocytic astrocytoma. The signalling pathway of mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of these tumours, so the search for effective targeted drugs with few side effects is the subject of current research. This article presents a clinical case of a boy with inoperable LGG, which was poorly responsive to established systemic treatment, so he received targeted treatment with an MEK inhibitor.

Gliomi nizkega gradusa (angl. low-grade gliomas, LGG) so najpogostejši primarni tumorji v osrednjem živčnem sistemu pri otrocih. Histološko so heterogena skupina možganskih tumorjev. Najpogostejši med njimi je pilocitni astrocitom. V njihovo patogenezo je med drugim vpletena signalna pot proteinske kinaze, aktivirane z mitogenom (angl. mitogen-activated protein kinase, MAPK), zato je iskanje učinkovitih tarčnih zdravil z malo neželenimi učinki osrednji predmet trenutnih raziskav. V prispevku predstavljamo klinični primer dečka z neoperabilnim LGG, ki je bil slabo odziven na uveljavljene sistemske oblike zdravljenja, zato smo se odločili za tarčno zdravljenje z inhibitorjem MEK.

Background: Slovenian children are facing considerable health challenges from the rapid social changes that influence their opportunity to engage in daily physical activity. Objective: To overlay the social changes to the established Report Card model as a means of contextualising the extreme changes in physical activity and fitness observed over several years. Methods: Benchmarks were graded for 10 core indicators, plus two (Sleep, Seasonal Variations). Active Healthy Kids Slovenia members met (predominantly via zoom) liaising with team leader(s) on a flexible, individual basis, based on coronavirus disease 2019 (COVID-19) regulations, over the ∼2-year assessment period of the project. Data were separated to the years prior to, ‘pre’ 2018–2020, and ‘during’ the global pandemic (2020–2021). Where sufficient data existed for both timeframes, grades were averaged to produce an overall grade. Results: Grade results are expressed as pre/during/final grade, where the final grade (bolded) is a straight average of the two preceding time epochs: Overall Physical Activity (A-/A-/A-), Organized Sport and Physical Activity (C+/C/C), Active Play (D/C+/C), Active Transport (C/INC/C), Sedentary Behaviour (B/C/C+), Physical Fitness (A+/A-/A), Family and Peers (B+/INC/B+), Schools (A/A/A), Community and Environment (A+/A+/A+), Government (A/F/D), Sleep (D-/INC/D-), Seasonal Variations (D/C-/D+). Conclusion: Although Slovenia has some of the most consistently physically-active children in the world, the effects of the COVID-19 pandemic exerted significant reductions in physical activity opportunities, and especially when coupled with funding re-distributions, resulted in the steepest decline of child physical fitness observed within the >35-year history of Slovenia's well-established national fitness surveillance system.

Abstract Objective Present study aimed to assess potential health risk in Slovenian adolescents due to inadequate diet and/or dietary supplement (DS) use. Methods Data on DS use, micronutrient intake (24-h recall), eating habits (FFQ), body height and mass were collected within ACDSi (Analysis of Children’s Development in Slovenia) cross-sectional study conducted in 2014. Adolescents enrolled in first year of 15 secondary schools (average (SD) age: 15.4 (0.7) years, N = 342) were included in the sample. Results Adolescents’ use of DS (especially multivitamins ingested as a popular drink (60%), magnesium (16%), and vitamin C (10%)) significantly contributed to their absolute intake of vitamins/minerals, resulting in higher percentage of DS users meeting reference values proposed by the nutrition societies of Germany, Austria, and Switzerland (D-A-CH recommendation). Simultaneously, DS users did not exceed the upper tolerable level proposed by the European Food Safety Authority for daily intake. With diet alone, adolescents consumed less than recommended amounts of the following vitamins/minerals: the intake was lowest for fat-soluble vitamins A, D, and E; water-soluble vitamins folate, biotin, and pantothenic acid; and minerals fluoride, iodine, chromium, and molybdenum. Suboptimal intake was due to the fact that around ¾ of adolescents consumed less than 54% of the recommended amounts (according to Optimized Mixed Diet (OMD) recommendations) for fruits, vegetables, milk/dairy products, fish, and cereals/cereal products. In contrast, the diet contributed to the consumption of 200–300% of D-A-CH minimum value for sodium. Furthermore, almost ¾ of adolescents exceeded the recommended amount for meat/meat products (320% of OMD) and sweet/salty snacks (453% of OMD). Conclusions Although DS use improved micronutrient intake in adolescents (especially vitamin C and magnesium), activities on public-health interventions should be focus to improve their diets, especially to achieve increased intakes of fruits, vegetables, cereals/cereal products and milk/dairy products, and to reduce consumption of sweet/salty snacks and meat products.

Optimized use of prophylactic or therapeutic donor lymphocyte infusions (DLI) is aimed at improving clinical outcomes in patients with malignant and non-malignant hematological diseases who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Memory T-lymphocytes (CD45RA−/CD45RO+) play a crucial role in immune reconstitution post-HSCT. The infusion of memory T cells is proven to be safe and effective in improving outcomes due to the enhanced reconstitution of immunity and increased protection against viremia, without exacerbating graft-versus-host disease (GVHD) risks. Studies indicate their persistence and efficacy in combating viral pathogens, suggesting a viable therapeutic avenue for patients. Conversely, using virus-specific T cells for viremia control presents challenges, such as regulatory hurdles, cost, and production time compared to CD45RA-memory T lymphocytes. Additionally, the modulation of regulatory T cells (Tregs) for therapeutic use has become an important area of investigation in GVHD, playing a pivotal role in immune tolerance modulation, potentially mitigating GVHD and reducing pharmacological immunosuppression requirements. Finally, donor T cell-mediated graft-versus-leukemia immune responses hold promise in curbing relapse rates post-HSCT, providing a multifaceted approach to therapeutic intervention in high-risk disease scenarios. This comprehensive review underscores the multifaceted roles of T lymphocytes in HSCT outcomes and identifies avenues for further research and clinical application.

Tetra pak packaging is one of the most frequently used types of packaging in the food industry. The recycling of the tetra pak packaging waste presents a difficult task because of its multi-layered, multi-component structure. In this study, the degradation of tetra pak packaging in subcritical (SubCW) and supercritical (SCW) water was investigated. The experiments were carried out in one (SCW) or two stages (SubCW and SCW), whereby the influence of the reaction temperature and time on the yield and composition of the products obtained was investigated. The maximum oil phase yield achieved in a one-stage and a two-stage degradation process was 60.7% and 65.5%, respectively. The oil and gas phases were composed of different types of hydrocarbons. Higher temperature and longer time led to higher amounts of saturated aliphatic hydrocarbons in both the oil and gas phases. The aqueous phase contained sugars (glucose, fructose) and sugar derivatives (levulinic acid, glyceraldehyde, furfurals). Based on these results, the degradation pathway of waste tetra pak packaging in SubCW and SCW was proposed. The results of the study show that the degradation of waste tetra pak packaging with SubCW and SCW is a promising recycling process.

Abstract High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development.

Feline atopic skin syndrome (FASS) describes allergic skin diseases in cats associated with sensitivity to environmental allergens. Allergen-specific immunotherapy (ASIT) aims to reduce or eliminate symptoms associated with subsequent exposure to the causative allergen. The primary outcome of this study was to determine if the quality of life (QoL) of cats and owners improved as a result of ASIT. The secondary outcome was to determine whether the QoL improved in cats treated with ASIT compared with cats treated symptomatically. Eight cats were included in the ASIT group (AG) and 6 cats in the control group (CG). Validated quality of life questionnaires were retrospectively completed by cat owners for the period before and after treatment. The QoL of cats improved significantly with ASIT. Cats were significantly less lazy, nervous, aggressive, restrained, preened less while sleeping and hid less, were less disturbed by consultations, were more playful and interactive with their environment, and had better appetites than before treatment. Owners felt significantly less physically exhausted and less emotionally distressed compared to before ASIT treatment and their expenses were significantly lower. On the contrary various symptomatic treatments did not significantly improve the quality of life of the cats or their owners in any of the terms. No serious side effects were observed with ASIT. The quality of life of animals suffering from chronic diseases is important as it determines the decisions of owners and veterinarians on the modalities of lifelong treatment. Validated questionnaires are still rarely used in veterinary practice and research.

Mental fatigue (MF) arises during prolonged demanding cognitive activity and results in acute feelings of tiredness and a decreased physical and/or cognitive performance capacity. An often-overlooked population that is significantly at risk for the development of MF are university students. The current study investigated the impact of prolonged in-person theoretical classes on the perceptions of MF, boredom, and sleepiness among 27 Slovenian university students (first-year physiotherapy). Their subjective experiences at various time points during a 4-h class interspersed with a 20 min break were assessed with a repeated measures ANOVA and consequent Bonferroni post-hoc tests (significance set at

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

Uvod: Motnje v razvoju spola (DSD) se pojavijo pri približno 1/5000 živorojenih otrok. Med nedavno odkritimi genetskimi vzroki za 46,xY DSD so različice v genu NR5A1, ki so odgovorne za širok fenotipski razpon. Prikaz primera: Predstavljamo primer donošenega novorojenčka z dvoumnimi genitalijami: levostransko tipno gonado v levi urogenitalni gubi volumna 1 ml, ter desnostransko tipno gonado v dimljah, odsotnost gubanosti in hiperpigmentacije kože urogenitalnih gub, kratek genitalni tuberkel dolžine 1,5 cm, labioskrotalni meatus sečnice (ocena zunanjih genitalij 4). Ultrazvok je pokazal prisotnost spolnih žlez, ki so kompatibilne s testisi, moški tip sečnice in odsotnost maternice ali jajčnikov. Kariotip je bil 46,xY in NGS je odkril patogeno heterozigotno podvajanje enega nukleotida 614dupC v genu NR5A1. Glede na to je bil določen moški spol in pri 8 mesecih je imel majhno strukturo penisa z dolžino < 2 cm, brez razvitega skrotuma in labioskrotalno hipospadijo. Orhidopeksija je bila opravljena v starosti 14 mesecev. Histologija gonad je kazala na prepubertetni testis. Razprava: Različice NR5A1 imajo spremenljivo ekspresivnost in nepopolno penetranco. Klinična slika pri bolnikih 46,xY s patogeno različico v genu NR5A1 sega od dvoumnih genitalij do normalnih ženskih zunanjih genitalij z virilizacijo v puberteti. Zdi se, da razvoj v puberteti ni močno povezan s stopnjo virilizacije ob rojstvu, saj velika večina kaže znake virilizacije v puberteti.

Introduction: Differences of Sex Development (DSD) occur in approximately 1/5000 live births. One of the recently found genetic causes for 46, xY DSD is NR5A1 gene variants, responsible for a broad phenotypic spectrum. Case Report: We present a case of a full-term newborn with ambiguous genitalia: one gonad located in the urogenital fold, the other inguinal, absence of wrinkling or hyperpigmentation of the urogenital folds’ skin, the short genital tubercle, and labio-scrotal urethral meatus (External Genital Score of 4). Male-type urethra and the absence of a uterus or ovaries were determined by ultrasound. The karyotype was 46, xY, and a pathogenic heterozygous single nucleotide duplication 614dupC in the NR5A1 gene was found by NGS. The decided gender of rearing was male. Orchidopexy was performed at age 14 months. The histology of the gonad was indicative of a prepubertal testis. Discussion: NR5A1 variants have variable expressivity and incomplete penetrance. 46, xY patients with a pathogenic variant in the NR5A1 gene range from ambiguous genitalia to normal female external genitalia with virilization at puberty. Pubertal development does not strongly correlate to the degree of virilization at birth, with the majority showing signs of virilization at pubertal age.

Relative energy deficiency syndrome develops in children and adolescents as a result of a negative energy balance due to insufficient energy intake during intense physical exercise regimens. This energy imbalance leads to impaired physiological function of multiple organ systems. Moreover, in children and adolescents, it presents a risk for the development of long-term consequences in terms of negative effects on growth, pubertal development and bone health. Early recognition and management are therefore crucial in this age group. Due to poor awareness among young athletes, their parents, coaches, medical staff, and a non-specific clinical presentation the illness is often overlooked.

Sindrom relativnega energijskega primanjkljaja se razvije pri otrocih in mladostnikih športnikih ob negativni energijski bilanci, ki je posledica nezadostnega vnosa energije glede na velike potrebe ob intenzivni telesni vadbi. Energijsko neravnovesje privede do motenj v delovanju več organskih sistemov. Pri otrocih in mladostnikih so posledice lahko dolgoročne in se kažejo kot neugoden vpliv na rast, pubertetni razvoj in zdravje kosti. Zgodnji prepoznava in obravnava sta tako v tej starostni skupini ključni. Zaradi pomanjkljive ozaveščenosti med mladimi športniki, njihovimi starši, trenerji in zdravstvenim osebjem ter nespecifične klinične slike bolezen pogosto spregledamo.

Abstract Objective Evaluate the adequacy of energy/macronutrient intake in adolescents according to the Slovenian national recommendations adopted from the recommendations of the German Nutrition Society and to identify differences in energy/macronutrient intake between differently active adolescents. Methods Data on energy and macronutrient intake (24-hour dietary recall), physical activity (SHAPES questionnaire), and anthropometric characteristics (body mass and height) of adolescents were obtained on a representative sample of first-year secondary school students (average (SD) age: 15.3 (0.5) years; N = 341), who were included in the national survey The Analysis of Children’s Development in Slovenia (ACDSi) in 2013/14. Results 75% of adolescents met the national recommendations for carbohydrates and proteins and 44% for fats, whereas only 10% of adolescents met the recommendations for energy intake. Energy/macronutrient intakes were significantly higher in vigorously physically active (VPA) boys compared to moderately (MPA) and less (LPA) physically active boys. No such differences were observed between girls of different physical activity levels. Conclusion Adolescents need to be encouraged to meet their energy needs according to gender and physical activity (especially VPA girls) and to reach for higher quality foods in adequate macronutrient proportions.

Abstract Population-based estimates of pathogenic variation burden in gynecologic cancer predisposition genes are a prerequisite for the development of effective precision public health strategies. This study aims to reveal the burden of pathogenic variants in a comprehensive set of clinically relevant breast, ovarian, and endometrial cancer genes in a large population-based study. We performed a rigorous manual classification procedure to identify pathogenic variants in a panel of 17 gynecologic cancer predisposition genes in a cohort of 7091 individuals, representing 0.35% of the general population. The population burden of pathogenic variants in hereditary gynecologic cancer-related genes in our study was 2.14%. Pathogenic variants in genes ATM, BRCA1, and CDH1 are significantly enriched and the burden of pathogenic variants in CHEK2 is decreased in our population compared to the control population. We have identified a high burden of pathogenic variants in several gynecologic cancer-related genes in the Slovenian population, most importantly in the BRCA1 gene.

Plastics are widely used due to their versatile properties and numerous applications. However, the proper management of plastic waste is a major challenge, even though it is recyclable. The process of repeated recycling can cause the quality of the material to decrease as unwanted contaminants and pollutants increase. This can affect the chemical recycling of plastics at the end of their life and the recovery of secondary products that can be used in other applications. In this study, the chemical degradation of virgin polypropylene (vPP) and recycled polypropylene (rPP) was investigated in supercritical water at a temperature of 450 °C and a reaction time of 15 to 240 min. The oil phase was the primary decomposition product and was obtained in high yield, which reached a maximum after 30 min of reaction time and was 96.9 % for vPP and 94.5 % for rPP. The results of our study show that there are some differences in the product composition depending on which material (vPP or rPP) is chemically recycled.

Sustainable societies of the future should be designed on the basis of a green public budgeting, as green public 79 spending and investment are the key drivers of sustainable development. Studies on green budgeting have so far tended to focus on green taxes and favourable regulatory regimes for specific sectors, although 14 out of 38 OECD countries have introduced these in some form. Based on secondary research of Slovenian budget documentation for the period from 2018 to 2022, our research findings show that green and sustainable content is weak, both in terms of content and scope. Only 11 out of 24 policies and only 23 out of over 3000 projects have included some ideas of the green and sustainable concept. Due to the evolving methodology and framework of green budgeting, the research challenge could be identified in a repeated and deeper analysis, including the targets and indicators in the coming years.

Rail transport is considered to be more environmentally friendly, economical and socially acceptable than other types of land transport, especially when compared to road transport. However, it can adversely affect wildlife by creating barriers to their movement, commonly known as the “barrier effect”, and by directly increasing mortality due to collisions with trains. Therefore, it is crucial to plan and implement mitigating measures to ensure ecological connectivity and reduce wildlife mortality caused by rail traffic. The primary focus of such measures should be on preventing animals from accessing and lingering on railway tracks, since trains typically cannot avoid collisions. Measures that effectively reduce the number of collisions without exacerbating the barrier effect are particularly desirable. In this review article, we focused on measures that have been proposed or implemented in railway infrastructure. Additionally, we examine recent research exploring the feasibility of alternative mitigation measures, such as warning systems tested in Canada and Sweden. The second part of the paper presents a proposal for a protocol designed to ensure migration corridors and minimize barrier effects. The protocol was developed based on relevant literature and previous studies, as well as our own experience in planning and implementing monitoring measures to reduce wildlife mortality (with a focus on ungulates) on roads, highways and freeways. It also incorporates an analysis of collisions between wildlife and trains on the Slovenian railways network during a selected five-year period.

Some previous research showed that average daily exposure to extremely low frequency (ELF) magnetic fields (MF) of more than 0.3 or 0.4 μT could potentially increase risk of childhood leukaemia.

Ultrasound (US) has been proven to be reliable in the assessment of early haemophilic arthropathy in the adult haemophilic population, however few studies so far focused on the reliability of US specifically in the paediatric haemophilic population. We were interested if the changing appearance of the growing bone hinders the ultrasonographic evaluation of the pathologic processes caused by haemophilic arthropathy. The aim of the study was to assess the reliability of US for evaluation of haemophilic arthropathy in children in comparison to magnetic resonance imaging (MRI).

Plant waste materials are important sources of bioactive compounds with remarkable health-promoting benefits. In particular, industrial by-products such as mango peels are sustainable sources of bioactive substances, with antioxidant, enzymatic, and antimicrobial activity. Appropriate processing is essential to obtain highly bioactive compounds for further use in generating value-added products for the food industry. The objective of the study was to investigate and compare the biological activity of compounds from fresh and dried mango peels obtained by different conventional methods and unconventional extraction methods using supercritical fluids (SFE). The highest total phenolic content (25.0 mg GAE/g DW) and the total content of eight phenolic compounds (829.92 µg/g DW) determined by LC-MS/MS were detected in dried mango peel extract obtained by the Soxhlet process (SE). SFE gave the highest content of proanthocyanidins (0.4 mg PAC/g DW). The ethanolic ultrasonic process (UAE) provided the highest antioxidant activity of the product (82.4%) using DPPH radical scavenging activity and total protein content (2.95 mg protein/g DW). Overall, the dried mango peels were richer in bioactive compounds (caffeic acid, chlorogenic acid, gallic acid, catechin, and hesperidin/neohesperidin), indicating successful preservation during air drying. Furthermore, outstanding polyphenol oxidase, superoxide dismutase (SOD), and lipase activities were detected in mango peel extracts. This is the first study in which remarkable antibacterial activities against the growth of Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) were evaluated by determining the microbial growth inhibition rate after 12 and 24 h incubation periods for mango peel extracts obtained by different methods. Ethanolic SE and UAE extracts from dried mango peels resulted in the lowest minimum inhibitory concentrations (MIC90) for all bacterial species tested. Mango peels are remarkable waste products that could contribute to the sustainable development of exceptional products with high-added value for various applications, especially as dietary supplements.

ITER is of key importance in the European fusion roadmap as it aims to prove the scientific and technological feasibility of fusion as a future energy source. The EUROfusion consortium of labs within Europe is contributing to the preparation of ITER scientific exploitation and operation and aspires to exploit ITER outcomes in view of DEMO. The paper provides an overview of the major progress obtained recently, carried out in the frame of the new (initiated in 2021) EUROfusion work-package called ‘ Pr eparation of I TER O peration’ (PrIO). The overview paper is directly supported by the eleven EUROfusion PrIO contributions given at the 29th Fusion Energy Conference (16–21 October 2023) London, UK [ https://www.iaea.org/events/fec2023 ]. The paper covers the following topics: (i) development and validation of tools in support to ITER operation (plasma breakdown/burn-through with evolving plasma volume, new infra-red synthetic diagnostic for off-line analysis and wall monitoring using Artificial Intelligence techniques, synthetic diagnostics development, development and exploitation of multi-machine databases); (ii) R&D for the radio-frequency ITER neutral beam sources leading to long duration of negative deuterium/hydrogen ions current extraction at ELISE and participation in the neutral beam test facility with progress on the ITER source SPIDER, and, the commissioning of the 1 MV high voltage accelerator (MITICA) with lessons learned for ITER; (iii) validation of neutronic tools for ITER nuclear operation following the second JET deuterium–tritium experimental campaigns carried out in 2021 and in 2023 (neutron streaming and shutdown dose rate calculation, water activation and activated corrosion products with advanced fluid dynamic simulation; irradiation of several materials under 14.1 MeV neutron flux etc).