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Abstract Self-sufficiency, climate change and increasing geopolitical risks have driven energy policies to make renewable energy sources dominant in the power production portfolios. The initial boom in the mid-2000s of global photovoltaic installations demonstrated the feasibility of the ambitious renewable energy targets. However, this rapid scale-up has introduced challenges, including price volatility and system integration issues. This communication calls the attention to these emerging challenges and offers quantitative insights on how rapid adoption of a more diversified photovoltaics deployment strategies can mitigate price volatilities, reduce fossil fuel dependence and steer Europe towards a forward-thinking sustainable energy pathway. The analysis reveals that as innovative bifacial photovoltaic systems are incorporated on a large-scale disruptive scenario, four main patterns emerge: economic value of solar production increases, base-load electricity price decreases, sun-rich countries expand their solar contributions, whereas nations with ample grid interconnections enhance their energy imports from neighbouring countries. It also underscores the importance of maintaining photovoltaics an attractive option for energy investors and traders in the future. Establishing this groundwork is critical since a successful integration of large-scale solar systems contributing to decrease price volatilities in Europe and US will carry significant repercussions for global energy policy formulation.

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was −2.8 (95% CI: −5.614–0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25–4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Abstract Calcium sparks are involved in major physiological and pathological processes in vertebrate muscles but have never been characterized in invertebrates. Here, dynamic confocal imaging on intact skeletal muscle cells isolated enzymatically from the adult honey bee legs allowed the first spatio-temporal characterization of subcellular calcium release events (CREs) in an insect species. The frequency of CREs, measured in x–y time lapse series, was higher than frequencies usually described in vertebrates. Honey bee CREs had a larger spatial spread at half maximum than their vertebrate counterparts and a slightly ellipsoidal shape, two characteristics that may be related to ultrastructural features specific to invertebrate cells. In line-scan experiments, the histogram of CREs’ duration followed a bimodal distribution, supporting the existence of both sparks and embers. Unlike in vertebrates, embers and sparks had similar amplitudes, a difference that could be related to genomic differences and/or excitation–contraction coupling specificities in honey bee skeletal muscle fibres. The first characterization of CREs from an arthropod which shows strong genomic, ultrastructural and physiological differences with vertebrates may help in improving the research field of sparkology and more generally the knowledge in invertebrates cell Ca2+ homeostasis, eventually leading to a better understanding of their roles and regulations in muscles but also the myotoxicity of new insecticides targeting ryanodine receptors.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Both the intake of beneficial olive oil and of harmful trans-fatty acids (TFAs) in consumed foods are of great significance in tumor biology. In our present study we examined the effects they exert on the expression patterns of miR-134, miR-132, miR-124-1, miR-9-3 and mTOR in the liver, spleen and kidney of mice treated with 7,12-dimethylbenz [a] anthracene (DMBA). Feeding of TFA-containing diet significantly increased the expression of all studied miRs and mTORC1 in all organs examined, except the expression of mTORC1 in the spleen and kidney. Diet containing olive oil significantly reduced the expression of miR-124-1, miR-9-3 and mTORC1 in the liver and spleen. In the kidney, apart from the mTORC1 gene, the expression of all miRs examined significantly decreased compared to the DMBA control. According to our results, the cell membrane protective, antioxidant, and anti-inflammatory effects of olive oil and the cell membrane damaging, inflammatory, and carcinogenic properties of TFA suggest negative feedback regulatory mechanisms. In contrast to our expectations, mTORC1 gene expression in the kidney has not been shown to be an appropriate biomarker-presumably, because the many complex effects that regulate mTOR expression may quench each other.

The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)—a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects.

Abstract The golden jackal (Canis aureus) is a reoccurring species in the centre of the Carpathian basin, in Hungary. In total, 31 golden jackal tissue samples were collected, from 8 white-coated, 2 black-coated and one mottled animal across Hungary. Sequences and fragment length polymorphisms were studied for white colour (MC1R), and for black coat colouration (CBD103). In each white animal, the most widespread mutation causing white fur colour in dogs in homozygous form was detected. Three animals were found to carry the mutation in heterozygous form. The two black golden jackals were heterozygous for the 3 bp deletion in CBD103 that mutation for black coat colouration in dogs, and one of them also carried the mutation causing white fur. None of the white animals showed signs of hybridization, but both the black and the mottled coloured individuals were found to be hybrids based on genetic testing. Kinship was found three times, twice between white animals, and once between a white animal and an agouti animal carrying the mutation of white coat. Our results confirm the findings that golden jackal–dog hybrids may occur without human intervention, and the detected mutation causing white fur colour in golden jackals could possibly be due to an early hybridization event.

Economic theory suggests that significant benefits can be realized, if two or more countries integrate their renewable support schemes and capitalize on the lowest cost renewable energy projects in merged markets. Hungary is one of the Central and Eastern European countries having a legal obligation to open their renewable auction schemes to other EU member states. This paper provides a model-based assessment of what such a cross-border cooperation could mean for Hungary and its neighbouring countries. Economic benefits are calculated and presented for the participating countries according to three pairwise cases for cooperation. Based on these outcomes, the paper concludes with the policy considerations and recommendations to shape the design of the opened auction scheme.

Small lowland watercourses, strongly exposed to anthropogenic activities and climate change, have received negligible odonatological attention. This study provides a revised checklist of three typical lowland small watercourses (Kállai-főfolyás, Konyári-Kálló and Ölyvös) within the Pannonian Lowland and presents the changes in their diversity over the past decades. Results revealed a significant biodiversity loss, with a 31.6% decline in Odonata fauna over the last 53 years. The upper and middle sections degraded the most, where the habitats have dried out or become intermittent. However, a diverse Odonata assemblage (1,277 individuals of 27 species) was observed at the 14 sampling sites of the three watercourses, containing protected and sensitive species (Somatochlora flavomaculata, Orthetrum brunneum, Aeshna isoceles, Libellula fulva). However, the low abundance of larval and exuvial forms (59 individuals of 13 species) suggests that the majority of the observed adults were developed in other watercourses. While recolonisation from nearby habitats is still possible, a parallel degradation of adjecent waterbodies could lead to an irreversible biodiversity loss.

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The Piezo1 mechanosensitive ion channel is abundant on several elements of the central nervous system including astrocytes. It has been already demonstrated that activation of these channels is able to elicit calcium waves on astrocytes, which contributes to the release of gliotransmitters. Astrocyte- and N-methyl-D-aspartate (NMDA) receptor-dependent slow inward currents (SICs) are hallmarks of astrocyte–neuron communication. These currents are triggered by glutamate released as gliotransmitter, which in turn activates neuronal NMDA receptors responsible for this inward current having slower kinetics than any synaptic events. In this project, we aimed to investigate whether Piezo1 activation and inhibition is able to alter spontaneous SIC activity of murine neocortical pyramidal neurons. When the Piezo1 opener Yoda1 was applied, the SIC frequency and the charge transfer by these events in a minute time was significantly increased. These changes were prevented by treating the preparations with the NMDA receptor inhibitor D-AP5. Furthermore, Yoda1 did not alter the spontaneous EPSC frequency and amplitude when SICs were absent. The Piezo1 inhibitor Dooku1 effectively reverted the actions of Yoda1 and decreased the rise time of SICs when applied alone. In conclusion, activation of Piezo1 channels is able to alter astrocyte–neuron communication. Via enhancement of SIC activity, astrocytic Piezo1 channels have the capacity to determine neuronal excitability.

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38–1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45–0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.

Background: Despite the fact that some results can be found for the logistics simulation in the literature, there is a lack of an experiment based on inner company data. Therefore, the study aimed to determine the potential need for this kind of solution by Zala County enterprises. Methods: As a first step, the paper presents the existing literature with the help of a literature review. Afterwards, questionnaire sampling was conducted among local enterprises. The paper applies several statistical methods (e.g., descriptive statistics, SPSS, exploratory factor analysis, and structural equation modeling) to the sample for the validation of the reorganization demand. Results: The study obtained a total of 147 complete responses from the 1022 invitations. An overwhelming majority of the respondents indicated regular and significant delays in their logistics processes, as well as the need for a new simulation method. Based on the SEM model, it has been observed that IT solutions are being utilized in an inefficient manner, resulting in logistical system issues and operational damages. Conclusion: The paper successfully identified a research gap, the research of which can have not only theoretical but also many practical benefits. Hopefully, the results will generate other academic research in this field.

BackgroundStaphylocoagulase (SCG) is a virulence factor of Staphylococcus aureus, one of the most lethal pathogens of our times. The complex of SCG with prothrombin (SCG/ProT) can clot fibrinogen, and SCG/ProT-induced fibrin and plasma clots have been described to show decreased mechanical and lytic resistance, which may contribute to septic emboli from infected cardiac vegetations. At infection sites, neutrophils can release DNA and histones, as parts of neutrophil extracellular traps (NETs), which in turn favor thrombosis, inhibit fibrinolysis and strengthen clot structure.ObjectivesTo characterize the combined effects of major NET-components (DNA, histone H1 and H3) on SCG/ProT-induced clot structure, mechanical and lytic stability.MethodsRecombinant SCG was used to clot purified fibrinogen and plasma. The kinetics of formation and lysis of fibrin and plasma clots containing H1 or core histones+/-DNA were followed by turbidimetry. Fibrin structure and mechanical stability were characterized with scanning electron microscopy, pressure-driven permeation, and oscillation rheometry.ResultsHistones and DNA favored the formation of thicker fibrin fibers and a more heterogeneous clot structure including high porosity with H1 histone, whereas low porosity with core histones and DNA. As opposed to previous observations with thrombin-induced clots, SCG/ProT-induced fibrin was not mechanically stabilized by histones. Similarly to thrombin-induced clots, the DNA-histone complexes prolonged fibrinolysis with tissue-type plasminogen activator (up to 2-fold). The anti-fibrinolytic effect of the DNA and DNA-H3 complex was observed in plasma clots too. Heparin (low molecular weight) accelerated the lysis of SCG/ProT-clots from plasma, even if DNA and histones were also present.ConclusionsIn the interplay of NETs and fibrin formed by SCG, DNA and histones promote structural heterogeneity in the clots, and fail to stabilize them against mechanical stress. The DNA-histone complexes render the SCG-fibrin more resistant to lysis and thereby less prone to embolization.

Abstract Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130–4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213–2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.

Abstract Obstructive sleep apnea (OSA) is associated with treatment‐resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta‐analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was −8.89 mmHg, 95% confidence interval (95% CI; −13.67 to −4.10, p

Introduction: Necrotizing fasciitis (NF) is a rapidly progressing soft tissue infection caused by fulminant tissue destruction with severe systemic toxicity and a high rate of mortality. It often holds a diagnostic challenge as initially the overlying tissue might appear unaffected. Early surgical intervention parallel with antibiotic therapy forms the basis of appropriate treatment. We present a case admitted with a suspicion of severe allergic reaction due to an insect bite, but finally diagnosed with a NF. Case report: A 17-year old female with swelling, pain and erythema of the left hand was admitted to Heim Pál National Pediatric Institute, Budapest, Hungary on 07.08.2022. She had an insect sting on the same localization one day prior admission. Due to tachycardia and low blood pressure on admission, she was initially mistreated as a severe allergic reaction (anaphylaxis). Laboratory parameters showed elevated inflammatory reaction. Examination of the dorsal area of the left hand revealed swelling and edema with pallor on the fingertips. At the center of the insect bite a pinhead size of a bluish area was seen with one pinhead size of a bulla. Broad spectrum antibiotics (ceftriaxone) was initially started, but sepsis progressed since tachycardia and hypotension persisted. On the second day of hospital stay imaging diagnostics (ultrasound and magnetic resonance imaging) were taken which revealed the signs of NF. High dose penicillin and clindamycin were started and surgical debridement of all necrotic tissues was done. Blood cultures as well as swab culture grew Streptococcus pyogenes. After 4 days of antibiotic treatment and surgical intervention, general condition and symptoms showed rapid improvement. She received 10 days of antibiotic treatment total. Conclusion: This case demonstrates that early diagnosis of NF is crucial. Immediate surgical intervention is needed, regardless of the imaging findings as the delay in surgical intervention can have a great impact on mortality.

Septins are considered the fourth component of the cytoskeleton with the septin7 isoform playing a critical role in the formation of diffusion barriers in phospholipid bilayers and intra- and extracellular scaffolds. While its importance has already been confirmed in different intracellular processes, very little is known about its role in skeletal muscle. Muscle regeneration was studied in a Sept7 conditional knock-down mouse model to prove the possible role of septin7 in this process. Sterile inflammation in skeletal muscle was induced which was followed by regeneration resulting in the upregulation of septin7 expression. Partial knock-down of Sept7 resulted in an increased number of inflammatory cells and myofibers containing central nuclei. Taken together, our data suggest that partial knock-down of Sept7 hinders the kinetics of muscle regeneration, indicating its crucial role in skeletal muscle functions.

Septin7 as a unique member of the GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be essential in the formation of hetero-oligomeric septin complexes. As a cytoskeletal component, Septin7 is involved in many important cellular processes. However, its contribution in striated muscle physiology is poorly described. In skeletal muscle, a highly orchestrated process of migration is crucial in the development of functional fibers and in regeneration. Here, we describe the pronounced appearance of Septin7 filaments and a continuous change of Septin7 protein architecture during the migration of myogenic cells. In Septin7 knockdown C2C12 cultures, the basic parameters of migration are significantly different, and the intracellular calcium concentration change in migrating cells are lower compared to that of scrambled cultures. Using a plant cytokinin, forchlorfenuron, to dampen septin dynamics, the altered behavior of the migrating cells is described, where Septin7-depleted cells are more resistant to the treatment. These results indicate the functional relevance of Septin7 in the migration of myoblasts, implying its contribution to muscle myogenesis and regeneration.

Abstract The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (

Introduction Bladder emptying abnormalities and cardiovascular autonomic dysfunction are manifestations of autonomic dysfunction in people with diabetes mellitus (DM), which are major causes of morbidity and mortality. Since they can reduce the quality of life, they are urgent to be addressed before resulting in complications. As uroflowmetry might determine autonomic neuropathy earlier than cardiovascular autonomic dysfunction symptoms occur, our aim is to detect early abnormalities in bladder muscle function in children with DM. We investigate the diagnostic accuracy of uroflowmetry. As a secondary aim, we compare the prevalence of uroflowmetry abnormalities to the appearance of measures of cardiovascular autonomic neuropathy. Finally, as an ancillary study, we examine the association of uroflowmetry with the appearance of peripheral neuropathy. These three aims, we feel, will put our results regarding uroflowmetry into an overall context of nerve disease early in the course of type 1 DM. To our knowledge, such an approach has heretofore not been performed.Methods and analysis This will be a prospective, observational, single-centre clinical study. Patients with DM fulfilling the inclusion criteria and healthy controls will have uroflowmetry examination, cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva manoeuvre, blood pressure and heart rate response to standing up, and to sustained handgrip) and nerve conduction test. The autonomic nervous system function will be examined by the reproducible and standardised cardiovascular reflex tests described by Ewing et al. During the examination, electrocardiogram (ECG) and blood pressure values will be recorded continuously. Heart rate response to deep inspiration will be executed to investigate the parasympathetic nervous system. Peripheral neuropathy will be evaluated by nerve conduction test. After a pilot period, when the first 50 diabetic and 50 healthy children will be assessed, sample size calculation will be carried out. The primary objective of this trial is to evaluate the diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of uroflowmetry. To do so, we compare uroflowmetry to the gold standard neuropathy tests, which are cardiovascular autonomic dysfunction tests (heart rate response to deep breathing, to Valsalva manoeuvre, blood pressure and heart rate response to standing up and to sustained handgrip).Ethics and dissemination Ethics approval was obtained from the Scientific and Research Ethics Committee of the Heim Pál National Paediatric Institute in Budapest, Hungary (registration number KUT-37/2021). Results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT05247840.