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Abstract Introduction The Harris Hip Score is the most widely used outcome measure for the assessment of hip pathologies. An official Slovenian version has not been culturally adapted and validated. The aim of this study was to create a Slovenian valid and reliable version of the HHS. Materials and method The HHS was translated and modified in Slovenian. The measurement properties of the Slovenian HHS were tested in 42 patients suffering from different hip pathologies. Reliability, responsiveness, construct validity, convergent/divergent validity and content validity of the Slovenian version of the HHS were tested. Results Only minor adaptation was required in the translation process. The internal consistency of the HHS expressed by Cronbach’s alpha was 0.94. The test–retest reliability expressed by the intraclass correlation coefficient was 0.983. The correlations of the HHS scale with the WOMAC scale (r = − 0.877) and the VAS scale (r = − 0.717) were statistically significant. The highest correlation between the HHS and SF-36 was with the General Health dimension (r = 0.61). while the lowest correlation was with the SF-36 Mental Health dimension (r = 0.43). MDC95% was 10.1. No floor or ceiling effects were found. Conclusion Slovenian version of HHS seems to has an acceptable level of reliability and validity. Slovenian HHS is short, comprehensible and easy to administer and interpret. Trial registration Approved by the Slovenian National Medical Ethics Committee (0120-46/2019/19).

The purpose of our research is to gain a better insight into what encourages young adults, in particular young women, to enter the teaching profession. The empirical part of the article is based on a pilot study including 132 students, with data collection being based on a survey approach using a questionnaire. The research attempts to address the context from which the desired characteristics of pre-service teachers with regard to their future employment arise. We have therefore tried to single out factors influencing the choice of teaching as a career, and to examine pre-service teachers’ attitudes towards the reputation of female and male teachers. The data obtained confirm the thesis that the predominance of women in the teaching profession(s) is an effect of the harmonisation of the female respondents’ habitus and their perception of the field they are entering. The perception of the teaching profession as a vocation (calling) that can be linked to the concepts of caring, giving and helping also proves to be very important. The data also confirms the thesis that the orientation towards life and work balance is important to our respondents of both genders.

Predmet obsežnega in natančnega preiskovanja Lilijane Burcar so procesi in oblike institucionalizacije patriarhata v kapitalizmu, politike, ki so v socializmu zrahljale institucionalni patriarhat, ukrepi, s katerim ga postsocialistične države ponovno vzpostavljajo, ter učinki pozasebljanja oskrbovalnega in varstvenega dela na družbenoekonomsko državljanstvo žensk.

Background. Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. Methods. This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. Results. Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE’s social network, which leads to (self-)isolation and social distrust. Conclusion. PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy.

In last ten, fifteen years, variety of disciplines literary throng the conceptualizations of identity. This plurality of discourses blurs the boundaries between disciplines and at the same time deepens them. The deconstruction positions in psychology, referring to Althusser's concept of interpellation, Lacanian psychoanalysis and Foucault's theorization of discourse and power relations do not try to define the boundaries and connections between the disciplines. However, in the analyses of the birth of psychological knowledge and their consequences the deconstruction position points out that psychological knowledge fatally reduces the factors constructing identity and subjectivity by limiting itself on individual and interpersonal. This article discusses two consequences of this reduction: this reduction leads to the conclusion that social differentiation is the effect of the individual differences in capacities and personal characteristics and at the same time this reduction impedes psychological knowledge in the analyses of its own role in the power relations.

Background: The assessment of sensory thresholds provides a method of examining the function of peripheral nerve fibers and their central connections. Quantitative sensory testing is a variant of conventional sensory testing wherein the goal is the quantification of the level of stimulation needed to produce a particular sensation. While thermal and vibratory testing are established methods in assessment of sensory thresholds, assessment of tactile thresholds with monofilaments is not used routinely. The purpose of this study was to assess the tactile thresholds in normal healthy population.Methods: In 39 healthy volunteers (19 men) aged 21 to 71 years, tactile thresholds were assessed with von Frey’s hair in 7 parts of the body bilaterally.Results: We found touch sensitivity not to be dependent on age or gender. The right side was significantly more sensitive in the lateral part of the leg (p=0.011) and the left side in the medial part of the arm (p=0.022). There were also significant differences between sites (pConclusions: Von Frey filaments allow the estimation of tactile thresholds without the need for complicated instrumentation.

Background: Frostbite is a local cold injury that may lead to loss of tissue, and result in disability. It is normally a consequence of prolonged exposure of unprotected regions to subzero ambient temperatures, which causes impairment of the microcirculation. In Slovenia, the main risk group for frostbite injury are mountain climbers. Frostbite is classified as either a superficialreversible injury, or an irreversible deep tissue injury. Superficial frostbite is managed in out-patient clinics, whereas hospital treatment is required for deep frostbite. The success of frostbite management depends a great deal on the field first aid and emergency medical treatment, as well as on the subsequent hospital treatment. The present study reports of the success of a protocol for hospital treatment of frostbite (Planica Protocol), comprising the early diagnosis with three-phase bone scintigraphy (TS), administration of appropriate medications, particularly iloprost, and initiation of hyperbaric oxygen treatment (HBOT). Patients and methods: A total of 27 mountain climbers presented with frostbite injury between 2000 and 2010. Of these, 16 suffered superficial injuries and were treated as outpatients. The remaining 11 mountaineers (2 females, and 9 males) suffered deep frostbite and were hospitalised. Frostbite injury was sustained at different altitudes (range: 2000 to 8848 meters above sea level) in the toes (n = 9; 82 %) and fingers (n = 2; 18 %). Some climbers (n = 9; 82 %) received field first aid, and some (n = 9; 82 %) also emergency medical treatment in the field. On admission to hospital, patients received the following treatpatient clinics, whereas hospital treatment is required for deep frostbite. The success of frostbite management depends a great deal on the field first aid and emergency medical treatment, as well as on the subsequent hospital treatment. The present study reports of the success of a protocol for hospital treatment of frostbite (Planica Protocol), comprising the early diagnosis with three-phase bone scintigraphy (TS), administration of appropriate medications, particularly iloprost, and initiation of hyperbaric oxygen treatment (HBOT). Patients and methods: A total of 27 mountain climbers presented with frostbite injury between 2000 and 2010. Of these, 16 suffered superficial injuries and were treated as outpatients. The remaining 11 mountaineers (2 females, and 9 males) suffered deep frostbite and were hospitalised. Frostbite injury was sustained at different altitudes (range: 2000 to 8848 meters above sea level) in the toes (n = 9; 82 %) and fingers (n = 2; 18 %). Some climbers (n = 9; 82 %) received field first aid, and some (n = 9; 82 %) also emergency medical treatment in the field. On admission to hospital, patients received the following treatment: early diagnosis with TS (n = 7; 64 %); pharmaceutcial interventions, including acetylsalicylic acid, low-molecular weight heparin, pentoxifylline, antibiotics, iloprost (n = 8; 64 %); and HBOT (n = 8; 73 %). Results: Of the 11 climbers with deep frostbite, tissue loss and amputation was avoided in 6 (55 %). Necrectomy (full amputation) was performed in 5 climbers (45 %): full-length digit amputation (n = 2), and part-length (one or two phalanges) amputations (n = 3). Amputation of the toes was required in both female climbers. Conclusions: Timely field first aid and emergency medical treatment is of paramount importance for a good outcome of frostbite injury. Early diagnostics using three-phase bone scintigraphy (TS) can assess the extent of tissue damage before final clinical manifestation of frostbite is fully developed. The Planica Protocol for the treatment of frostbite injury, comprising early diagnostics (TS), proper medication (acetylsalicylic acid, low-molecular weight heparin, pentoxifylline, antibiotics, iloprost), and HBOT appears to provide a beneficial outcome of deep frostbite injury.

Background Peripheral neuropathy is a common complication of diabetes, whereby pain control is the most difficult issue. The outcomes of existing treatment options are far from satisfactory and the results of studies comparing them are indecisive. Hence, we aimed at comparing the effect of treating pain with transcutaneous electrical nerve stimulation (TENS), pregabalin and their combination in patients with painful diabetic neuropathy (PDN), including the quality-of-life aspect. Methods A randomized clinical trial was planned with 69 PDN patients divided into three equally sized groups receiving TENS, pregabalin or combined treatment. Because of early dropouts from the pregabalin and combination group due to side effects, randomization was abandoned during recruitment phase and all remaining patients were assigned to TENS, resulting in group sizes of 46, 5 and 14, respectively. Assessments for pain relief and quality of life were performed at baseline, at the end of three-week treatment, and one moth after the end of treatment. Results Observed treatment effects did not differ between the groups. Statistically significant and clinically meaningful reduction of average and worst pain was achieved. Patients rated their quality of life better especially in the bodily pain domain of Short Form-36. One month post treatment, all observed effects were still present. Pain reduction correlated mainly with improvement of physical functioning domain. Conclusions Since TENS did not differ in efficacy from pregabalin and combined treatment, and does not have side effects, it appears to be a viable addition or even alternative to other analgesic modalities in PDN.

American foulbrood (AFB) is a serious infectious disease of honeybees ( Apis mellifera ) caused by Paenibacillus larvae . Increased P. larvae count in hive-related material is associated with an increased risk of AFB. Here, we quantified P. larvae cells in 106 adult bee and 97 hive debris samples using quantitative PCR (qPCR); 66/106 adult bee and 66/97 hive debris samples were collected simultaneously from the same bee colony (paired-sample design). The corresponding bee colonies were also examined for the presence of AFB clinical signs. A binary logistic regression model to distinguish between AFB-affected and unaffected honeybee colonies showed a strong diagnostic accuracy of both sample types for predicting the onset of AFB based on P. larvae counts determined by qPCR. The colonies with a P. larvae count greater than 4.5 log cells/adult bee or 7.3 log cells/mL hive debris had a 50% probability of being clinically affected and were categorized as high-risk. The AFB-unaffected colonies had significantly lower P. larvae counts than the AFB-affected colonies, but the latter did not differ significantly in P. larvae counts in relation to the severity of clinical signs. Both bee-related sample types had a high diagnostic value for predicting disease outcome based on P. larvae counts. These results improve the understanding of the relationship between P. larvae counts and AFB occurrence, which is essential for early detection of high-risk colonies.

Objective: The objective of study was to assess 24-h urinary Na and K excretion and estimate the average salt and K intakes in a nationally representative sample of the adult population of Slovenia., Design: A nationally representative cross-sectional study was conducted in four stages between September and November 2022: study questionnaire, physical measurements, 24-h urine collection and laboratory analysis., Setting: Slovenia., Participants: We invited 2000 adult, non-institutionalised inhabitants of Slovenia, aged between 25 and 64 years. A stratified two-staged sample was selected from this population by the Statistical Office of Slovenia, using sampling from the Central Population Register. According to the WHO methodology, additional eligibility criteria were screened before participating. A total of 518 individuals participated in all four stages of the study, resulting in a response rate of 30 %., Results: The mean 24-h urinary Na excretion was 168 mmol/d (95 % CI 156, 180), which corresponds to a mean estimated intake of 10·3 g salt/d (95 % CI 9·6, 11·1). Mean 24-h urinary K excretion was 65·4 mmol/d (95 % CI 63·2, 67·5), and the estimated mean K intake was 2·93 g/d (95 % CI 2·84, 3·03). There were statistically significant differences in mean intakes between males and females. The mean sodium-to-potassium ratio was 2·7 (95 % CI 2·5, 2·8)., Conclusions: The study results highlighted that the salt intake in the adult population of Slovenia remains much higher than recommended by the WHO, and K intakes are insufficient, as most participants did not meet the recommendations.

Nintedanib, an intracellular inhibitor that targets multiple tyrosine kinase, is an important drug for the treatment of pulmonary fibrosis. Until now, no studies have been published reporting the nintedanib tolerability or its efficacy in patients with chronic pulmonary lung disease and chronic kidney disease comorbidity. The safety, efficacy and pharmacokinetics of nintedanib have not been studied in patients with severe renal impairment (creatinine clearance < 30 mL/min) and for this reason it is contraindicated in these patients. We describe a case of use of nintedanib in a patient affected by idiopathic pulmonary fibrosis (IPF) who started, from 2022, nintedanib 150 mg twice a day with careful monitoring of liver and kidney function. Due to the onset of stage 3/4 chronic kidney disease associated with proteinuria, nintedanib was suspended for two months, and the patient received Prednisone at a dose of 12.5 mg/day. During the two months of suspension, the renal function did not improve, unlike the respiratory status worsened. In the past a renal biopsy was performed which showed no correlation with nintedanib use. Nintedanib therapy started again following the decline in lung function and desaturation below 90% in the 6-min walking test (6MWT). Patient showed a good tolerability of nintedanib with sporadic episode of diarrhea and an improvement of pulmonary function leading to a stable state of chronic pulmonary fibrosis disease. For this reason, in mutual agreement with the patient, we decided to maintain nintedanib therapy even when the patient required hemodialysis. No toxic effects appeared. This case report revealed the safety of nintedinab in patient with concomitant kidney failure, but more studies are necessary.

The present opinion deals with the re-evaluation of shellac (E 904) when used as a food additive and with the new application on the extension of use of shellac (E 904) in dietary foods for special medical purposes. The Panel derived an acceptable daily intake (ADI) of 4 mg/kg body weight (bw) per day for wax-free shellac (E 904) produced by physical decolouring, based on a NOAEL of 400 mg/kg bw per day and applying an uncertainty factor of 100. The Panel concluded that the ADI of 4 mg/kg bw per day should be considered temporary for wax-free shellac (E 904) produced by chemical bleaching, while new data are generated on the identity and levels of the organochlorine impurities in E 904. This ADI is not applicable for wax-containing shellac as a food additive. For several age groups, the ADI was exceeded at the 95th percentile in the non-brand-loyal exposure assessment scenario and maximum level exposure assessment scenario. Considering the low exceedance and the fact that both the exposure estimation and the toxicological evaluation of shellac were conservative, the panel concluded that the calculated exceedance of the ADI does not indicate a safety concern. The Panel recommended to the European Commission separating specifications for E 904 depending on the manufacturing process, chemical bleaching and physical decolouring, because they result in different impurities; revising the definition of the food additive to include a description of each manufacturing process; deleting information on wax-containing shellac from the EU specifications; revising the acid value for wax-free shellac produced by chemical bleaching; lowering the maximum limit for lead; to consider introducing limits for other toxic elements potentially present in shellac; including a maximum limit for chloroform and total inorganic chloride in the EU specification for shellac produced by chemical bleaching., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (∼IC 50 (4 h) 26 µg/ml, ∼IC 50 (24 h) 6-8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD's safety profile, paving the way for further exploration of CBD's therapeutic applications and potential adverse effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance., Competing Interests: The authors report no competing interests., (© 2024 The Author(s).)

Ascorbic acid (AA) plays a crucial role in both the proliferation and chondrogenic differentiation potential of mesenchymal stem/medicinal signalling cells (MSCs); these are both key aspects of their general therapeutic use and their increasing use in veterinary medicine. Current immunomodulatory therapies require efficient expansion of MSCs in the laboratory, while emerging tissue regeneration strategies, such as cartilage or bone repair, aim to use differentiated MSCs and modulate the expression of chondrogenic and hypertrophic markers. Our aim was to investigate whether the addition of AA to the growth medium enhances the proliferation of canine adipose-derived MSCs (cAMSCs) grown on standard plastic surfaces and whether it affects chondrogenic differentiation potential on silk fibroin (SF) films. We assessed cell viability with trypan blue and proliferation potential by calculating population doubling. Chondrogenic induction on SF films was assessed by Alcian blue staining and gene expression analysis of chondrogenic and hypertrophic genes. The results showed that growth medium with AA significantly enhanced the proliferation of cAMSCs without affecting cell viability and modulated the expression of chondrogenic and hypertrophic genes of cAMSCs grown on SF films. Our results suggest that AA may be used in growth medium for expansion of cAMSCs and, at the same time, provide the basis for future studies to investigate the role of AA and SF in chondrogenic differentiation of MSCs.

Honeybee diseases are one of the most significant and most common causes of honeybee colonies' weakness and death. An early diagnosis of subclinical infections is necessary to implement precautionary and control measures. Sampling debris from hive bottom boards is simple, non-invasive, and cheap. In this study, we collected winter debris samples in apiaries located in the continental part of Croatia. We used molecular methods, PCR and qPCR, for the first time to analyze those samples. Laboratory results were compared with the health condition and strength of honeybee colonies at an apiary in spring. Our study successfully identified the presence and quantity of various pathogens, including the presence of Vairimorpha spp. ( Nosema spp.), quintefied Paenibacillus larvae , Acute Bee Paralysis Virus (ABPV), Black Queen Cell Virus (BQCV), Deformed Wing Virus (DWV), and Sacbrood Virus (SBV). However, our analysis did not detect Melissococcus plutonius , Crithidia mellificae , Lotmaria passim , and Aethina tumida . Samples of winter debris were also examined for the presence and quantification of the V. destructor mites, and their natural mite fall was observed in spring. Honeybee colonies were simultaneously infected by an average of four to six pathogens. Some observed honeybee colonies developed characteristic symptoms, while others did not survive the winter.

The present study introduces an advanced surface modification approach combining electrochemical anodization and non-thermal plasma treatment, tailored for biomedical applications on stainless steel grade 316L (SS316L) surfaces. Nanopores with various diameters (100-300 nm) were synthesized with electrochemical anodization, and samples were further modified with non-thermal oxygen plasma. The surface properties of SS316L surfaces were examined by scanning electron microscopy, atomic force microscopy, X-ray photoemission spectroscopy, and Water contact angle measurements. It has been shown that a combination of electrochemical anodization and plasma treatment significantly alters the surface properties of SS316L and affects its interactions with blood platelets and human coronary cells. Optimal performance is attained on the anodized specimen featuring pores within the 150-300 nm diameter range, subjected to subsequent oxygen plasma treatment; the absence of platelet adhesion was observed. At the same time, the sample demonstrated good endothelialization and a reduction in smooth muscle cell adhesion compared to the untreated SS316L and the sample with smaller pores (100-150 nm). This novel surface modification strategy has significant implications for improving biocompatibility and performance of SS316L in biomedical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In this study, we investigated the prognostic potential of DNA ploidy., Materials and Methods: Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was measured and a Ploidy Score (PS) was generated., Results: Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time (PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant (p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence free survival within CAPRA-S low-risk cohort., Conclusion: DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Algal biostimulants are increasingly integral to vegetable cultivation due to their capacity to boost yield, alleviate abiotic and biotic stress, and enhance overall crop quality. This study evaluated the impact of two commercially available algal-based biostimulants on cucumber ( Cucumis sativus L.), examining their effects on yield, number of fruits, dry weight, color, flesh thickness, skin thickness, plastid pigments, and tocopherol content. Both biostimulant treatments resulted in a roughly 13% decrease in yield and fruit number compared to the control treatment. Notably, the biostimulants positively influenced the fruit brightness parameter (L*), leading to darker fruits. Fitostim ® algal biostimulant exhibited a positive effect on dry weight during the initial harvest. The predominant pigments were chlorophyll a and chlorophyll b (constituting 80% of all analyzed pigments), and the most abundant tocopherol was α-tocopherol, comprising 80% to 90% of tocopherols. Skin tissues contained significantly higher levels of pigments and tocopherols compared to flesh. Both biostimulants caused a notable decrease in total tocopherol content in the skin at the first harvest, with reductions of 19.91 mg/kg DW for Phylgreen ® and 9.43 mg/kg DW for Fitostim ® algae. The study underscores the variable efficacy of biostimulants, emphasizing their dependence on the specific biostimulant type and fruit part. The application of biostimulants has the potential to substantially enhance the internal quality of cucumbers, particularly in terms of plastid pigments and tocopherols, offering potential health benefits for consumers.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which are characterised by inflammation of small-medium-sized vessels. Progressive understanding of these diseases has allowed researchers and clinicians to start discussing nailfold video capillaroscopy (NVC) as a future tool for many applications in daily practice. Today, NVC plays a well-established and validated role in differentiating primary from secondary Raynaud's phenomenon correlated with scleroderma. Nevertheless, there has not been sufficient attention paid to its real potential in the ANCA-associated vasculitis. In fact, the role of NVC in vasculitis has never been defined and studied in a multicentre and multinational study. In this review, we carried out a literature analysis to identify and synthesise the possible role of capillaroscopy for patients with ANCA-associated vasculitis., Methods: Critical research was performed in the electronic archive (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until November 2023. The following search words were searched in the databases in all possible combinations: capillaroscopy, video capillaroscopy, nailfold-video capillaroscopy, ANCA-associated vasculitis, vasculitis, granulomatosis with polyangiitis, EGPA, and microscopic polyangiitis., Results: The search identified 102 unique search results. After the evaluation, eight articles were selected for further study. The literature reported that capillaroscopy investigations documented non-specific abnormalities in 70-80% of AAV patients. Several patients showed neoangiogenesis, capillary loss, microhaemorrhages, and bushy and enlarged capillaries as the most frequent findings. Furthermore, the difference between active phase and non-active phase in AAV patients was clearly discernible. The non-active phase showed similar rates of capillaroscopy alterations compared to the healthy subjects, but the active phase had higher rates in almost all common abnormalities instead., Conclusions: Microvascular nailfold changes, observed in patients affected by vasculitis, may correlate with the outcome of these patients. However, these non-specific abnormalities may help in the diagnosis of vasculitis. As such, new analysis analyses are necessary to confirm our results.

The 'QuantitatEVs: multiscale analyses, from bulk to single vesicle' workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV-associated molecular components and EV biophysical features, which are considered the core of EV-associated biomarker discovery and validation for their clinical translation. The in-person-only workshop was held in Trento, Italy, from January 31 st to February 2 nd , 2023, and continued in Milan on February 3 rd with "Next Generation EVs", a satellite event dedicated to early career researchers (ECR). This report summarizes the main topics and outcomes of the workshop., Competing Interests: Conflicts of interest: The authors declare no conflict of interest.

Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor-dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre-analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood-EV), a tool to record and report information about pre-analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre-analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence-based optimization of pre-analytical protocols through meta-analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter-laboratory comparative EV studies, and (iv) improve the peer review process., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

This study aimed to determine the content and composition of bioactive compounds in autochthonous rose hips ( R. pendulina , R. spinosissima , and R. gallica ) and to compare them with the content of bioactive compounds in some cultivars ('Harstad', 'Bourgogne', 'Mount Everest', 'Poppius', 'Fruhlingsduft', 'Single Cherry', 'Fruhlingsmorgen', 'Violacea', and 'Splendens') derived from these main species. Due to insufficient information on how bioactive compound content changes when crossing roses, this study also sought to ascertain whether modern rose hip cultivars are still a sufficiently rich source of bioactive compounds and could, therefore, be potentially used as a functional food. All material was collected in the Arboretum Volčji Potok (Slovenia). The ascorbic acid content was highest in the 'Harstad' cultivar (12.79 g/kg FW), and the total organic acid content varied from 1.57 g/kg FW ( R. spinosissima ) to 34.39 g/kg FW ('Harstad'). Of all the carotenoids analyzed, only lycopene and β -carotene were present in all the samples. The total carotenoid content was highest in the 'Fruhlingsmorgen' cultivar (100.84 mg/kg FW), derived from R. spinosissima , and lowest in the main species, R. spinosissima (9.26 mg/kg FW). It can be concluded, therefore, that the content of bioactive compounds in rose hips of modern cultivars is generally lower than in rose hips of old cultivars and original species included in this study. The research results confirm that modern breeding strategies are mainly focused on goals such as abundant flowering and resistance to diseases and pests and not so much on the content of bioactive compounds.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor β (TGF-β) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

Background: Sarcoidosis is a systemic inflammatory disease characterized by an altered inflammatory response., Objective: The aim of this study was to evaluate whether immune system alterations detected by lymphocyte typing in peripheral blood correlate with the severity of sarcoidosis, calculated according to two separate severity scores proposed by Wasfi in 2006 and Hamzeh in 2010., Materials and Methods: Eighty-one patients were recruited, and clinical data and laboratory tests at the time of diagnosis were obtained in order to assess the severity index score and investigate any statistically significant correlation with the cytofluorimetry data., Results: Our data demonstrated that none of the two scores show an association with the level of total lymphocytes or lymphocyte subclasses., Limitations: First of all, the sample taken into consideration is small. The assessment was performed only at disease onset and not during the disease. Furthermore, the severity scores do not take into account disease activity (measured by PET/CT or gallium scintigraphy)., Conclusions: Lymphocyte subpopulation values at the time of diagnosis do not appear to correlate with disease severity at onset.

Due to the lack of studies on chestnut metabolites, this study was conducted to identify and quantify the major phenolic constituents in chestnuts. Data were compared with the three most commonly grown interspecific hybrids of C. sativa and C. crenata ('Bouche de Betizac', 'Marsol', and 'Maraval') and three "native" accessions of C. sativa . High-performance liquid chromatography coupled with mass spectrometry was used to identify and quantify these compounds. Four dicarboxylic acid derivatives, five hydroxybenzoic acids, nine hydroxycinnamic acids, and three flavanols were identified and quantified, most of them for the first time. Hydroxybenzoic acids were the major phenolic compounds in all chestnut cultivars/accessions, followed by flavanols, dicarboxylic acid derivatives, and hydroxycinnamic acids. Of all the compounds studied, the (epi)catechin dimer was the most abundant in chestnut. The assumption that cultivars from commercial hybrids have a better and different metabolic profile than "native" accessions was refuted.

Our research aimed to investigate the primary and secondary metabolites of rosehips and petals of R. gallica in comparison with R. subcanina . R. gallica was chosen because it is still unexplored in terms of various bioactive substances and is strongly present in Slovenia. Given that roses are generally very variable and unstudied, our research will contribute to greater transparency and knowledge of the bioactive composition of rosehips and petals. We found a strong positive correlation between the total content of phenolics and ascorbic acid, between the total content of organic acids and the total content of carotenoids, and between the total content of sugars and the total content of organic acids. Hips of R. gallica contained higher amounts of sugars, ascorbic acid, and carotenoids than R. subcanina . Based on the composition of phenolic compounds in the petals, it is possible to distinguish between the two species. Among all the phenolic compounds in the petals, both genotypes are richest in gallotannins, followed by flavonols. Among anthocyanins, cyanidin-3-glucoside was determined, the content of which was also higher in R. gallica . It can be concluded that the studied hips had an extremely low sugar content and, consequently, an extremely high organic acid content. The content of carotenoids in hips was in the lower range of the average content compared to data from the literature. By optimizing the harvesting time, we could obtain a higher content of carotenoids, which could potentially be used for industrial purposes. However, we found that the analyzed petals were a rich source of phenolic compounds, which benefit the human body and could be potentially used in the food and cosmetic industries.

The present study deals with the comparison of traditional fruit processing methods on medlar fruits and their effects on sugar content, organic acids, and phenolic composition in the medlar fruit variety 'Domača nešplja'. The study aimed to analyze which processing methods can be used to make technologically mature medlar fruits that are not yet suitable for consumption edible and to maintain their good chemical quality. The two major sugars in medlars are fructose (59.30 g/kg FW) and glucose (54.43 g/kg FW), and the most abundant organic acids present are malic (8.44 g/kg FW) and quinic acid (8.77 g/kg FW). A total of 38 different phenolic compounds were identified in the medlar fruits: 13 phenolic acids, 9 flavanols, 1 flavone, 3 flavanones, and 12 flavonol glycosides. To explicate: phenolic acids (532.85 mg/kg FW) and flavanols (375.21 mg/kg FW) predominated; neochlorogenic acid had the highest content among phenolic acids; and procyanidins were the most abundant flavanols. The analysis observed statistical differences in metabolite content amongst fruits treated differently (technologically ripe fruits (harvested from the three fruits), edible fruits (technologically ripe fruits stored at 8 °C for 25 days), fruits exposed to the hoarfrost (temperature -1 °C to -4 °C), fruits heated at 60 °C (3 h), and frozen fruits (at -20 °C for 2 months). The lowest levels of fructose (191.77-195.1 g/kg DW) and sorbitol (29.35-31.3 g/kg DW) were detected in the heated and edible fruits. Edible fruits had a 30% lower content of organic acids than technologically ripe fruits and a five times lower content of flavanols, whereas flavonols had an 18.7 times lower content of phenolic acids than technologically ripe fruits. Heating the fruits to 60 °C resulted in a 40% increase in total phenolic compounds in medlars. The results of the study indicate that exposure of medlar fruit to hoarfrost does not significantly affect the chemical quality of the fruit and only minimally alters the composition of sugars, acids, and phenolic compounds. The processing of medlar fruit with hoarfrost, therefore, remains the most suitable method of fruit bletting.

The focus of this experiment was to compare the color and metabolic profile of apple juice from the red-fleshed cultivar 'Baya Marisa' with the white-fleshed cultivar 'Golden Delicious'. The changes in the phenolic compounds, organic acids, and sugar content during high-temperature short-time pasteurization and after one year of storage under different storage conditions were analyzed. A total of 26 individual phenolic compounds were identified and quantified. The total analyzed phenolics content (TAPC) decreased after pasteurization of the juices of both cultivars. The TAPC of fresh 'Baya Marisa' juice after pasteurization increased or remained the same compared to one-year stored 'Baya Marisa' juice, depending on the storage method. The sucrose content of the apple juice of both cultivars remained the same after pasteurization; interestingly, it decreased significantly after one year of storage, while the fructose and glucose content remained the same after pasteurization and increased significantly after one year of storage for both cultivars.

Black fruits, especially blackberries and black currants, are highly appreciated by consumers due to their nutraceutical properties, which have reported health benefits. This study aimed to assess the fruit quality of the blackberry (cv. 'Čačanska Bestrna') and black currant (cv. 'Čačanska Crna') created at the Fruit Research Institute, Čačak (Republic of Serbia) by evaluating basic quality parameters (fruit weight, soluble solids), and content of primary (sugars and organic acids) and secondary (phenolic compounds) metabolites. Additionally, the study examined the quality of frozen and long-term frozen storage (6, 9, and 12 months). The results showed that 'Čačanska Crna' contained a high level of total soluble solids (15.23°Bx), sugars (93.06 mg g -1 ), and a high index of sweetness (159.48) as well as a high content of acids (34.35 mg g -1 ) in the fruit. Both species were found to contain forty-seven phenolic compounds, including phenolic acids, flavanols, and anthocyanins, analyzed using high performance liquid chromatography-mass spectrometry (HPLC-MS). 'Čačanska Bestrna' had the highest amounts of phenolic acids (66.85 mg 100 g -1 ) and flavanols (53.99 mg 100 g -1 ), whereas 'Čačanska Crna' showed the highest levels of flavonols (8.57 mg 100 g -1 ) and anthocyanins (139.11 mg 100 g -1 ). Furthermore, the study revealed that anthocyanins were the most abundant phenolic group in both blackberries and black currants, and their levels remained constant during frozen storage. The sugar content in both species remained unchanged, while the acid concentration increased over time in blackberries but remained consistent in black currants. Overall, the findings highlight the superior phenolic content, particularly anthocyanins, of the cultivars with black fruits selected in Serbia. These cultivars have great commercial potential for the fresh market and processing. Moreover, the study suggests that frozen storage is an effective method for preserving their quality and beneficial properties.

The use of compost made from the leaves of Juglans regia has long been controversial because of its inhibitory effect due to the presence of juglone. Therefore, the aim of our study was to replicate the typical habits of farmers and gardeners, where the dried leaves are collected at the end of the season and placed in a composter. Then, the effects of the different treatments on the yield of the plant (lettuce), secondary metabolism, and possible toxicity of the compost of the grown plant were evaluated. The lowest yield of lettuce was obtained in soil with composted walnut and hazelnut leaves, while the highest yield was recorded in in soil with compost control, soil with composted walnut leaves and grass with the addition of composting agent and soil with composted walnut leaves with addition of composting agent. Some allelochemicals were still present in the compost but at such low levels that they did not affect yield. We suggest that dry walnut leaves and cut grass can be used for composting, while dry hazelnut leaves still contain some allelochemicals after two years that significantly inhibit plant growth and thus yield, so we would not recommend their use for composting.

Aim: Recently, a patient-reported experience measure (PREM) was developed in Slovenia to assess patients' experiences with outpatient specialist healthcare clinics. The aim of this study was to evaluate the psychometric properties (including factor structure, reliability, convergent validity, and response distribution) of the questionnaire., Methods: The sample consisted of 8,406 adult participants treated in 171 specialist clinics from different medical fields. Participants voluntarily and anonymously responded to either the paper or online survey., Results: Descriptive statistics show meaningful response patterns with a general tendency towards favourable assessments. The psychometric analyses of the scales evaluating doctor's and nurses' work, respectively, generally showed a good fit of the unidimensional factor model as well as the Rasch model, high factor loadings and very good to satisfactory reliability. The Rasch scaling showed that these scales were most informative for patients with relatively unfavourable experience ratings., Conclusions: The results are similar to those found in previous evaluations of PREMs in other countries. Given its good psychometric properties, the Slovenian PREM can be recommended for healthcare evaluations in Slovenia and as a model for the development of similar PREMs in other countries., Competing Interests: CONFLICTS OF INTEREST The authors declare that no conflicts of interest exist., (© 2023 Gregor Sočan et al., published by Sciendo.)

The genus Rosa is very extensive and variable, so it remains very unpredictable and uninvestigated. This also holds true for values of secondary metabolites in rose hips, which are important for several purposes (human diet, protection of plants against pests, etc.). The aim of our study was to determine the content of phenolic compounds in the hips of R. × R. glauca , R. corymbifera , R. gallica and R. subcanina , which grow wild in nature in southwestern Slovenia. We examined the content of phenolic compounds in different parts of rose hips, in the flesh with skin and in the seeds, depending on the individual species, over a period of two years, 2020 and 2021. We also considered the influence of environmental conditions on the content of the mentioned compounds. In both years, the content of phenolic compounds was higher in the flesh with skin than in the seeds. Considering the total content of phenolic compounds in the flesh with skin, R. gallica stands out (15,767.21 mg/kg FW), but the hips of this species accumulated the lowest number of different phenolic compounds. The lowest content of total phenolic compounds (TPC) was found in R. corymbifera, in the year 2021 (3501.38 mg/kg FW). The content of TPC (in both observed years) in the seeds varied between 1263.08 mg/kg FW ( R. subcanina ) and 3247.89 mg/kg FW ( R. × R. glauca ). Among the anthocyanins, cyanidin-3-glucoside was determined, which was predominant in R. gallica (28.78 mg/kg FW), and at least was determined in R. subcanina (1.13 mg/kg FW). When comparing the two years of the period (2020-2021), we found that 2021 was more favorable for the formation of phenolic compounds in the seeds, but 2020 in the flesh with skin.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are an absolute necessity for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have already been proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based on the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With a False Discovery Rate (FDR) threshold of 0.1, only six circRNAs passed the filtering and only one of them remained statistically significant after Bonferroni correction: hsa&#95;circ&#95;0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa&#95;circ&#95;0060762 and CSE1L. CSE1L is a member of the importin β family and mediates inhibition of TDP-43 aggregation; the central pathogenicity in ALS and hsa&#95;circ&#95;0060762 has binding sites for several miRNAs that have been already proposed as biomarkers for ALS. In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa&#95;circ&#95;0060762. Hsa&#95;circ&#95;0060762 and CSE1L thus represent novel potential peripheral blood biomarkers and therapeutic targets for ALS.

Background and Objectives : The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension ( p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions : IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Probiotics are known for their positive effects on the gut microbiota. There is growing evidence that the infant gut and skin colonization have a role in the development of the immune system, which may be helpful in the prevention and treatment of atopic dermatitis. This systematic review focused on evaluating the effect of single-strain probiotic lactobacilli consumption on treating children's atopic dermatitis. Seventeen randomized placebo-controlled trials with the primary outcome of the Scoring Atopic Dermatitis (SCORAD) index were included in the systematic review. Clinical trials using single-strain lactobacilli were included. The search was conducted until October 2022 using PubMed, ScienceDirect, Web of Science, Cochrane library and manual searches. The Joanna Briggs Institute appraisal tool was used to assess the quality of the included studies. Meta-analyses and sub meta-analyses were performed using Cochrane Collaboration methodology. Due to different methods of reporting the SCORAD index, only 14 clinical trials with 1124 children were included in the meta-analysis (574 in the single-strain probiotic lactobacilli group and 550 in the placebo group) and showed that single-strain probiotic lactobacilli statistically significantly reduced the SCORAD index compared to the placebo in children with atopic dermatitis (mean difference [MD]: -4.50; 95% confidence interval [CI]: -7.50 to -1.49; Z = 2.93; p = 0.003; heterogeneity I 2 = 90%). The subgroup meta-analysis showed that strains of Limosilactobacillus fermentum were significantly more effective than strains of Lactiplantibacillus plantarum , Lacticaseibacillus paracasei or Lacticaseibacillus rhamnosus . A longer treatment time and younger treatment age statistically significantly reduced symptoms of atopic dermatitis. The result of this systematic review and meta-analysis shows that certain single-strain probiotic lactobacilli are more successful than others in reducing atopic dermatitis severity in children. Therefore, careful consideration to strain selection, treatment time and the age of the treated patients are important factors in enhancing the effectiveness of reducing atopic dermatitis in children when choosing probiotic single-strain lactobacilli.

The effects of salicylic acid (SA) and one of its better-known derivatives-methyl salicylic acid (MeSA)-on the infection of apple fruits with the fungus Monilinia laxa , which causes brown rot, were investigated. Since research to date has focused on preventive effects, we also focused on the curative use of SA and MeSA. Curative use of SA and MeSA slowed the progression of the infection. In contrast, preventive use was generally unsuccessful. HPLC-MS was used to analyze the content of phenolic compounds in apple peels in healthy and boundary peel tissues around lesions. The boundary tissue around the lesions of untreated infected apple peel had up to 2.2-times higher content of total analyzed phenolics (TAPs) than that in the control. Flavanols, hydroxycinnamic acids and dihydrochalcones were also higher in the boundary tissue. During the curative treatment with salicylates, the ratio of TAP content between healthy and boundary tissue was lower (SA up to 1.2-times higher and MeSA up to 1.3-times higher content of TAPs in boundary compared to those in healthy tissue) at the expense of also increasing the content in healthy tissues. The results confirm that salicylates and infection with the fungus M. laxa cause an increased content of phenolic compounds. Curative use of salicylates has a greater potential than preventive use in infection control.

Background: COVID-19 infection has been associated with paradoxical thromboembolism through a patent foramen ovale (PFO) and ischaemic stroke. Such events have not been reported after COVID-19 vaccination. The aim of the present study was to investigate PFO-associated stroke during the mass COVID-19 vaccination in Slovenia. Methods: This prospective study, conducted between 26 December 2020 and 31 March 2022, enrolled consecutive patients (≥18 years) with PFO-associated stroke referred for a percutaneous closure to a single interventional facility in Slovenia. Results: A total of 953,546 people aged between 18 and 70 years received at least one dose of a COVID-19 vaccine approved by the European Medicines Agency. Of the 28 patients presenting with PFO-associated stroke, 12 patients (42.9%) were vaccinated prior to the event, of whom nine were women and three were men, aged between 21 and 70 years. Stroke occurred within 35 days after vaccination in six patients (50%). Clinical presentation included motor dysphasia, paresis, vertigo, ataxia, paraesthesia, headache, diplopia and hemianopia. At hospital discharge, 11 patients (91.6%) had at least one residual ischaemic lesion. Conclusion: A temporal coincidence of COVID-19 vaccination and PFO-associated stroke has been described. A potential cause-effect relationship may only be hypothesised., Competing Interests: Disclosure: The authors have no conflicts of interest to declare. Funding: The study was funded by the Center for Cardiovascular Diseases MC Medicor, Izola, Slovenia (EU). Data availability: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Author contributions: Conceptualisation: MR, NCS, MZ, MN; data curation: MR, NCS, MZ, MN; formal analysis: MR, NCS, MZ, MN; funding acquisition: MR, NCS, MZ, MN; investigation: MR, NCS, MZ, MN; methodology: MR, NCS, MZ, MN; project administration: MR, NCS, MZ, MN; resources: MR, NCS, MZ, MN; software: MR, NCS, MZ, MN; supervision: MR, NCS, MZ, MN; validation: MR, NCS, MZ, MN; visualisation: MR, NCS, MZ, MN; writing – original draft preparation: MR, NCS, MZ, MN; writing – review and editing: MR, NCS, MZ, MN Ethics: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the National Ethics Committee (Number 93/11/12). Consent: All patients have given written informed consent., (Copyright © 2023, Radcliffe Cardiology.)

This study investigated the association between certain genetic variations and the risk of developing proliferative vitreoretinopathy (PVR) after surgery. The study was conducted on 192 patients with primary rhegmatogenous retinal detachment (RRD) who underwent 3-port pars plana vitrectomy (PPV). The distribution of single nucleotide polymorphisms (SNPs) located in genes involved in inflammation and oxidative stress associated with PVR pathways were analyzed among patients with and without postoperative PVR grade C1 or higher. A total of 7 defined SNPs of 5 genes were selected for genotyping: rs4880 ( SOD2 ); rs1001179 ( CAT ); rs1050450 ( GPX1 ); rs1143623, rs16944, rs1071676 ( IL1B ); rs2910164 ( MIR146A ) using competitive allele-specific polymerase chain reaction. The association of SNPs with PVR risk was evaluated using logistic regression. Furthermore, the possible association of SNPs with postoperative clinical parameters was evaluated using non-parametric tests. The difference between two genotype frequencies between patients with or without PVR grade C1 or higher was found to be statistically significant: SOD2 rs4880 and IL1B rs1071676. Carriers of at least one polymorphic IL1B rs1071676 GG allele appeared to have better postoperative best-corrected visual acuity only in patients without PVR ( p = 0.070). Our study suggests that certain genetic variations may play a role in the development of PVR after surgery. These findings may have important implications for identifying patients at higher risk for PVR and developing new treatments.

Strawberries are appreciated by consumers for their characteristic taste and health benefits, which enhance their demand throughout the year. Everbearing strawberries can produce fruits for a longer period and could thus meet this demand, but the fruit quality depends on environmental factors and the cultivar. This study focused on the effect of environmental conditions on the physical attributes and the composition of everbearing Capri cultivar fruit harvested from the end of June to the end of October. A positive correlation was observed between temperature and organic acid content (r = 0.87), and a positive correlation was observed between sunshine duration, anthocyanin (r = 0.87) and phenolic compound contents (r = 0.89). Additionally, the composition of sugars was affected by the environmental conditions. While strawberries harvested towards the end of October, when lower temperatures predominated, were larger in size and had a higher sugar/acid ratio, fruit harvested in the middle of August, when there were longer periods of sunshine, had higher anthocyanin and phenolic compound contents. In conclusion, strawberries with higher sugar/acid ratios are obtained when temperatures are lower, while strawberries exposed to longer periods of sunshine are richer in health-promoting compounds.

The aim of this study was to compare peeled and unpeeled dehydrated apple slices of the red-fleshed 'Baya Marisa' and the white-fleshed 'Golden Delicious', to analyze the difference in the content of sugars, organic acids, and phenolic compounds during the heat process of dehydration, and to compare it with our previous study on fresh apples of the same cultivar. The purpose of these study was to see how many primary and secondary metabolites are lost in the dehydration process to better understand what is ingested by consumers in terms of nutritional value. A total of 30 phenolic compounds were identified and quantified, some of them for the first time. The total analyzed phenolic content (TAPC) of the unpeeled dehydrated apple slices was 1.7 times higher in 'Golden Delicious' than in 'Baya Marisa'. The unpeeled dehydrated apple slices of 'Golden Delicious' had higher total hydroxycinnamic acid (2.7×) and dihydrochalcone (1.2×) content. The peeled dehydrated apple slices of 'Baya Marisa' had higher total dihydrochalcone (2.2×) and total flavanol (2.2×) content compared to 'Golden Delicious'. The content of citric and malic acids was higher in the unpeeled and peeled dehydrated apple slices of 'Baya Marisa', compared to 'Golden Delicious'. The content of ascorbic acid was higher in the unpeeled (1.6×) and peeled (1.8×) dried apple slices of 'Baya Marisa'. The content of fructose and glucose was 1.4 times higher in the unpeeled dried apple slices of 'Golden Delicious'.

Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease ( p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 ( p = 0.039) and for DLCO ( p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.

Over the past 20 years, numerous tyrosine kinase inhibitors (TKIs) have been introduced for targeted therapy of various types of malignancies. Due to frequent and increasing use, leading to eventual excretion with body fluids, their residues have been found in hospital and household wastewaters as well as surface water. However, the effects of TKI residues in the environment on aquatic organisms are poorly described. In the present study, we investigated the cytotoxic and genotoxic effects of five selected TKIs, namely erlotinib (ERL), dasatinib (DAS), nilotinib (NIL), regorafenib (REG), and sorafenib (SOR), using the in vitro zebrafish liver cell (ZFL) model. Cytotoxicity was determined using the MTS assay and propidium iodide (PI) live/dead staining by flow cytometry. DAS, SOR, and REG decreased ZFL cell viability dose- and time-dependently, with DAS being the most cytotoxic TKI studied. ERL and NIL did not affect viability at concentrations up to their maximum solubility; however, NIL was the only TKI that significantly decreased the proportion of PI negative cells as determined by the flow cytometry. Cell cycle progression analyses showed that DAS, ERL, REG, and SOR caused the cell cycle arrest of ZFL cells in the G0/G1 phase, with a concomitant decrease of cells in the S-phase fraction. No data could be obtained for NIL due to severe DNA fragmentation. The genotoxic activity of the investigated TKIs was evaluated using comet and cytokinesis block micronucleus (CBMN) assays. The dose-dependent induction of DNA single strand breaks was induced by NIL (≥2 μM), DAS (≥0.006 μM), and REG (≥0.8 μM), with DAS being the most potent. None of the TKIs studied induced micronuclei formation. These results suggest that normal non-target fish liver cells are sensitive to the TKIs studied in a concentration range similar to those previously reported for human cancer cell lines. Although the TKI concentrations that induced adverse effects in exposed ZFL cells are several orders of magnitude higher than those currently expected in the aquatic environment, the observed DNA damage and cell cycle effects suggest that residues of TKIs in the environment may pose a hazard to non-intentionally exposed organisms living in environments contaminated with TKIs.

Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS's slowly progressive characteristic, which is often accompanied by other neurological comorbidities, its diagnosis remains challenging. Perturbations in vesicle-mediated transport and autophagy as well as cell-autonomous disease initiation in glutamatergic neurons have been revealed in ALS. The use of extracellular vesicles (EVs) may be key in accessing pathologically relevant tissues for ALS, as EVs can cross the blood-brain barrier and be isolated from the blood. The number and content of EVs may provide indications of the disease pathogenesis, its stage, and prognosis. In this review, we collected a recent study aiming at the identification of EVs as a biomarker of ALS with respect to the size, quantity, and content of EVs in the biological fluids of patients compared to controls.