Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1.

BACKGROUND: The sodium channel and clathrin linker 1 gene (SCLT1) has been involved in the pathogenesis of various ciliopathy disorders such as Bardet-Biedl syndrome, orofaciodigital syndrome type IX, and Senior-Løken syndrome. Detailed exams are warranted to outline all clinical features. Here, we present a family with a milder phenotype of SCLT1-related disease. MATERIAL AND METHODS: Comprehensive eye examination including fundus images, OCT, color vision, visual fields and electroretinography were performed. Affected individuals were assessed by a pediatrician and a medical geneticist for systemic features of ciliopathy. Investigations included echocardiography, abdominal ultrasonography, blood work-up for diabetes, liver and kidney function. Genetic testing included NGS retinal dystrophy panel, segregation analysis and transcriptome sequencing. RESULTS: Two male children, age 10 and 8 years, were affected with attention deficit hyperactivity disorder (ADHD), obesity and mild photophobia. The ophthalmic exam revealed reduced best-corrected visual acuity (BCVA), strabismus, hyperopia, astigmatism and moderate red-green defects. Milder changes suggesting photoreceptors disease were found on retinal imaging. Electroretinogram confirmed cone photoreceptors dysfunction. Genetic testing revealed a homozygous likely pathogenic, splice-site variant in SCLT1 gene NM_144643.3: c.1439 + 1del in the proband and in the affected brother. The unaffected parents were heterozygous for the SCLT1 variant. Transcriptome sequencing showed retention of intron 16 in the proband. CONCLUSIONS: In this report, we highlight the importance of further extensive diagnostics in patients with unexplained reduced vision, strabismus, refractive errors and ADHD spectrum disorders. SCLT1-related retinal degeneration is very rare and isolated reduced function of cone photoreceptors has not previously been observed.

High average daily temperature in summer and the incidence of thrombolytic treatment for acute ischemic stroke.

INTRODUCTION: Meteorological factors can increase stroke risk; however, their impact is not precisely understood. Heat waves during summer increase total mortality. Therefore, we hypothesized that the average daily temperature in summer may correlate with the incidence of thrombolytic treatment for acute ischemic stroke in Budapest and Pest County, Hungary. METHODS: We analyzed the relationship between the average daily temperature in summer months and the daily number of thrombolytic treatments (TT) performed with the indication of acute ischemic stroke between 1st June and 31st August each year from 2007 to 2016. The analysis was also performed after the omission of the data of the last day of the months due to possible psychosocial impact reported in our previous study. Spearman's correlation was used for statistical analysis. RESULTS: No significant correlation was found between the average summer daily temperature and the number of TT in the entire sample of the 10-year period. When omitting the data of the last day of each month, positive correlations were suspected in 2014 (r=0.225, P=0.034) and 2015 (r=0.276, P=0.009). CONCLUSION: Our findings did not confirm an association between the average daily temperature in summer and the daily number of TT throughout the examined 10-year period. However, importantly, in 2014 and 2015, the years with the highest average daily temperatures in this period, a positive correlation was found. The level of correlation is modest, indicating that risk factors, both meteorological and non-meteorological, other than the average temperature, play equally important roles in determining the incidence of thrombolytic treatment for acute ischemic stroke on the population level.

Untargeted metabolomic analyses support the main phylogenetic groups of the common plant-associated Alternaria fungi isolated from grapevine (Vitis vinifera).

Alternaria, a cosmopolitan fungal genus is a dominant member of the grapevine (Vitis vinifera) microbiome. Several Alternaria species are known to produce a variety of secondary metabolites, which are particularly relevant to plant protection and food safety in field crops. According to previous findings, the majority of Alternaria species inhabiting grapevine belong to Alternaria sect. Alternaria. However, the phylogenetic diversity and secondary metabolite production of the distinct Alternaria species has remained unclear. In this study, our aim was to examine the genetic and metabolic diversity of endophytic Alternaria isolates associated with the above-ground tissues of the grapevine. Altogether, 270 Alternaria isolates were collected from asymptomatic leaves and grape clusters of different grapevine varieties in the Eger wine region of Hungary. After analyses of the nuclear ribosomal DNA internal transcribed spacer (ITS) and RNA polymerase second largest subunit (rpb2) sequences, 170 isolates were chosen for further analyses. Sequences of the Alternaria major allergen gene (Alt a 1), endopolygalacturonase (endoPG), OPA10-2, and KOG1058 were also included in the phylogenetic analyses. Identification of secondary metabolites and metabolite profiling of the isolates were performed using high-performance liquid chromatography (HPLC)-high-resolution tandem mass spectrometry (HR-MS/MS). The multilocus phylogeny results revealed two distinct groups in grapevine, namely A. alternata and the A. arborescens species complex (AASC). Eight main metabolites were identified in all collected Alternaria isolates, regardless of their affiliation to the species and lineages. Multivariate analyses of untargeted metabolites found no clear separations; however, a partial least squares-discriminant analysis model was able to successfully discriminate between the metabolic datasets from isolates belonging to the AASC and A. alternata. By conducting univariate analysis based on the discriminant ability of the metabolites, we also identified several features exhibiting large and significant variation between A. alternata and the AASC. The separation of these groups may suggest functional differences, which may also play a role in the functioning of the plant microbiome.

[The new target population of stroke awareness campaign: Kindergarten students]. / "Stroke-ovi". A lakossági felvilágosítás új célközönsége: az óvodások.

Background and purpose:

 Thrombolysis and/or thrombectomy have been proven effective in the treatment of acute ischemic stroke. Due to the narrow time window, the number of patients suitable for these treatments is low. The main limitation is the pre-hospital stage, few people call an ambulance in time. The delay may be caused by the population’s insufficient health knowledge, but also by the loneliness and isolation of the population most prone to stroke. Among the latter, there are many grandparents who spend considerable time with their grandchildren. This gave rise to the idea of educating even younger children about the symptoms of a stroke, enabling them to call an ambulance if necessary. To this end, we adapted the Angels Initiative project previously tested in Greece. The Hungarian pilot study Budapest District XII. took place in district kindergartens. The Angels’ original role-playing program could not be implemented due to the COVID epidemic, so the necessity called for a new, Hungarian version: the online “Stroke Ovi” program. We introduced this in several stages, and in the third we also carried out an impact study.

 We adapted the Angels Initiative’s international program and its Hungarian translation to our program. We prepared the original, live role-playing form, with a parent meeting in the selected “test kindergarten”. Due to the uncertainly lingering impact of the COVID epidemic, we reevaluated our plan, using the Hungarian storybook and take-home workbook created in the meantime, we developed our own online version in several kindergartens in Budapest. We held 10 and then 25 minute sessions a week for 5 weeks. In the third educational cycle, which always targets new groups, we already examined the impact of the program by taking pre- and post-tests, in which not only the children but also their parents participated. In addition to neurologists and kindergarten teachers, we also included psychologists and speech therapists in our work, because we believed that in a social environment that includes parents and children, results can only be achieved through multidisciplinary cooperation.

 In the third cycle of the program, tests were taken before (pre-test) and after (post-test) among children and their parents. We only took into account those answers where we received an evaluable answer in the survey before and after the program. Our most important results: 1. there was no negative change in any question, so it was not the case that the total score of any question in the pre-test was higher than in the post-test. 2. The children learned that not only adults can call the ambulance. 3. Before the program, all children were already aware that if “someone is very ill”, the ambulance should be called. 4. Among the questions about stroke symptoms, it is important that hemiparesis, facial paresis and speech/language disorder are clear symptoms for children. Based on the parental questionnaires, the knowledge of the adults can be judged to be very good. The same number of correct answers were received during the pre-test and the post-test, on the basis of which we could not calculate a transfer effect. However, it is important that the parents considered the program useful, motivating and important for the children, so cooperation can be expected in the future.

The Hungarian “Stroke Ovi” program has so far proven to be clearly effective. This was proven by the impact assessments even if, instead of the original role-playing game, we implemented it “only” online due to the COVID epidemic. This constraint also forced and created a new “Hungarian version”. Despite the small number of samples caused by the circumstances, we consider this positive effect to be measurable. However, as the main result and evidence, we evaluated the children’s reaction, which took shape in spontaneous drawings and displayed professional values in addition to positive emotional reactions, such as the drawing of ambulances, the recurring representation of the 112 number. With the involvement of the media, we think online education is also a good option in the series of stroke campaigns, but we think the original role-playing form is really effective. At the same time, we can see that the application of the new method requires great caution due to the education of developing children. For this reason, results can only be achieved through social and multidisciplinary cooperation involving neurologists, psychologists, kindergarten teachers, and parents.

Characterization of the Sterol 24-C-Methyltransferase Genes Reveals a Network of Alternative Sterol Biosynthetic Pathways in Mucor lusitanicus.

Certain members of the order Mucorales can cause a life-threatening, often-fatal systemic infection called mucormycosis. Mucormycosis has a high mortality rate, which can reach 96 to 100% depending on the underlying condition of the patient. Mucorales species are intrinsically resistant to most antifungal agents, such as most of the azoles, which makes mucormycosis treatment challenging. The main target of azoles is the lanosterol 14α-demethylase (Erg11), which is responsible for an essential step in the biosynthesis of ergosterol, the main sterol component of the fungal membrane. Mutations in the erg11 gene can be associated with azole resistance; however, resistance can also be mediated by loss of function or mutation of other ergosterol biosynthetic enzymes, such as the sterol 24-C-methyltransferase (Erg6). The genome of Mucor lusitanicus encodes three putative erg6 genes (i.e., erg6a, erg6b, and erg6c). In this study, the role of erg6 genes in azole resistance of Mucor was analyzed by generating and analyzing knockout mutants constructed using the CRISPR-Cas9 technique. Susceptibility testing of the mutants suggested that one of the three genes, erg6b, plays a crucial role in the azole resistance of Mucor. The sterol composition of erg6b knockout mutants was significantly altered compared to that of the original strain, and it revealed the presence of at least four alternative sterol biosynthesis pathways leading to formation of ergosterol and other alternative, nontoxic sterol products. Dynamic operation of these pathways and the switching of biosynthesis from one to the other in response to azole treatment could significantly contribute to avoiding the effects of azoles by these fungi. IMPORTANCE The fungal membrane contains ergosterol instead of cholesterol, which offers a specific point of attack for the defense against pathogenic fungi. Indeed, most antifungal agents target ergosterol or its biosynthesis. Mucormycoses-causing fungi are resistant to most antifungal agents, including most of the azoles. For this reason, the drugs of choice to treat such infections are limited. The exploration of ergosterol biosynthesis is therefore of fundamental importance to understand the azole resistance of mucormycosis-causing fungi and to develop possible new control strategies. Characterization of sterol 24-C-methyltransferase demonstrated its role in the azole resistance and virulence of M. lusitanicus. Moreover, our experiments suggest that there are at least four alternative pathways for the biosynthesis of sterols in Mucor. Switching between pathways may contribute to the maintenance of azole resistance.

Disentangling the effects of terroir, season, and vintage on the grapevine fungal pathobiome.

The composition, diversity and dynamics of microbial communities associated with grapevines may be influenced by various environmental factors, including terroir, vintage, and season. Among these factors, terroir stands out as a unique possible determinant of the pathobiome, the community of plant-associated pathogens. This study employed high-throughput molecular techniques, including metabarcoding and network analysis, to investigate the compositional dynamics of grapevine fungal pathobiome across three microhabitats (soil, woody tissue, and bark) using the Furmint cultivar. Samples were collected during late winter and late summer in 2020 and 2021, across three distinct terroirs in Hungary's Tokaj wine region. Of the 123 plant pathogenic genera found, Diplodia, Phaeomoniella, and Fusarium displayed the highest richness in bark, wood, and soil, respectively. Both richness and abundance exhibited significant disparities across microhabitats, with plant pathogenic fungi known to cause grapevine trunk diseases (GTDs) demonstrating highest richness and abundance in wood and bark samples, and non-GTD pathogens prevailed soil. Abundance and richness, however, followed distinct patterns Terroir accounted for a substantial portion of the variance in fungal community composition, ranging from 14.46 to 24.67%. Season and vintage also contributed to the variation, explaining 1.84 to 2.98% and 3.67 to 6.39% of the variance, respectively. Notably, significant compositional differences in fungi between healthy and diseased grapevines were only identified in wood and bark samples. Cooccurrence networks analysis, using both unweighted and weighted metrics, revealed intricate relationships among pathogenic fungal genera. This involved mostly positive associations, potentially suggesting synergism, and a few negative relationships, potentially suggesting antagonistic interactions. In essence, the observed differences among terroirs may stem from environmental filtering due to varied edaphic and mesoclimatic conditions. Temporal weather and vine management practices could explain seasonal and vintage fungal dynamics. This study provides insights into the compositional dynamics of grapevine fungal pathobiome across different microhabitats, terroirs, seasons, and health statuses. The findings emphasize the importance of considering network-based approaches in studying microbial communities and have implications for developing improved viticultural plant health strategies.

Mutations in Rht-B1 Locus May Negatively Affect Frost Tolerance in Bread Wheat.

The wheat semi-dwarfing genes Rht (Reduced height) are widely distributed among the contemporary wheat varieties. These genes also exert pleiotropic effects on plant tolerance towards various abiotic stressors. In this work, frost tolerance was studied in three near-isogenic lines of the facultative variety 'April Bearded' (AB), carrying the wild type allele Rht-B1a (tall phenotype), and the mutant alleles Rht-B1b (semi-dwarf) and Rht-B1c (dwarf), and was further compared with the tolerance of a typical winter type variety, 'Mv Beres'. The level of freezing tolerance was decreasing in the order 'Mv Beres' > AB Rht-B1a > AB Rht-B1b > AB Rht-B1c. To explain the observed differences, cold acclimation-related processes were studied: the expression of six cold-related genes, the phenylpropanoid pathway, carbohydrates, amino acids, polyamines and compounds in the tricarboxylic acid cycle. To achieve this, a comprehensive approach was applied, involving targeted analyses and untargeted metabolomics screening with the help of gas chromatography/liquid chromatography­mass spectrometry setups. Several cold-related processes exhibited similar changes in these genotypes; indeed, the accumulation of eight putrescine and agmatine derivatives, 17 flavones and numerous oligosaccharides (max. degree of polymerization 18) was associated with the level of freezing tolerance in the 'April Bearded' lines. In summary, the mutant Rht alleles may further decrease the generally low frost tolerance of the Rht-B1a, and, based on the metabolomics study, the mechanisms of frost tolerance may differ for a typical winter variety and a facultative variety. Present results point to the complex nature of frost resistance.

Exploring Relationships among Grapevine Chemical and Physiological Parameters and Leaf and Berry Mycobiome Composition.

Improving our knowledge on biotic and abiotic factors that influence the composition of the grapevine mycobiome is of great agricultural significance, due to potential effects on plant health, productivity, and wine characteristics. Here, we assessed the influence of scion cultivar on the diversity and composition of fungal communities in the berries and leaves of three different cultivars. We generated DNA metabarcoding data, and statistically compared the richness, relative abundance, and composition of several functional groups of fungi among cultivars, which are partly explained by measured differences in chemical composition of leaves and berries and physiological traits of leaves. Fungal communities in leaves and berries show contrasting patterns among cultivars. The richness and relative abundance of fungal functional groups statistically differ among berry and leaf samples, but less so among cultivars. Community composition of the dominant functional groups of fungi, i.e., plant pathogens in leaves and saprotrophs in berries, differs significantly among cultivars. We also detect cultivar-level differences in the macro- and microelement content of the leaves, and in acidity and sugar concentration of berries. Our findings suggest that there appears to be a relatively diverse set of fungi that make up the grapevine mycobiome at the sampled terroir that spans several cultivars, and that both berry and leaf mycobiomes are likely influenced by the chemical characteristics of berries and leaves, e.g., pH and the availability of nutrients and simple carbohydrates. Finally, the correlation between fungal community composition and physiological variables in leaves is noteworthy, and merits further research to explore causality. Our findings offer novel insights into the microbial dynamics of grapevine considering plant chemistry and physiology, with implications for viticulture.

A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver.

BACKGROUND: Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. RESULTS: We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model. CONCLUSIONS: We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.

Identification and Molecular Analysis of Putative Self-Incompatibility Ribonuclease Alleles in an Extreme Polyploid Species, Prunus laurocerasus L.

Cherry laurel (Prunus laurocerasus L.) is an extreme polyploid (2n = 22x) species of the Rosaceae family where gametophytic self-incompatibility (GSI) prevents inbreeding. This study was carried out to identify the S-ribonuclease alleles (S-RNases) of P. laurocerasus using PCR amplification of the first and second intron region of the S-RNase gene, cloning and sequencing. A total of 23 putative S-RNase alleles (S 1-S 20, S 5 m, S 13 m, and S 18 m) were sequenced from the second (C2) to the fifth conserved region (C5), and they shared significant homology to other Prunus S-RNases. The length of the sequenced amplicons ranged from 505 to 1,544 bp, and similar sizes prevented the proper discrimination of some alleles based on PCR analysis. We have found three putatively non-functional alleles (S 5 m, S 18 m, and S 9) coding for truncated proteins. Although firm conclusions cannot be drawn, our data seem to support that heteroallelic pollen cannot induce self-compatibility in this polyploid Prunus species. The identities in the deduced amino acid sequences between the P. laurocerasus and other Prunus S-RNases ranged between 44 and 100%, without a discontinuity gap separating the identity percentages of trans-specific and more distantly related alleles. The phylogenetic position, the identities in nucleotide sequences of the second intron and in deduced amino acid sequences found one or more trans-specific alleles for all but S 10, S 14, S 18, and S 20 cherry laurel RNases. The analysis of mutational frequencies in trans-specific allele pairs indicated the region RC4-C5 accepts the most amino acid replacements and hence it may contribute to allele-specificity. Our results form the basis of future studies to confirm the existence and function of the GSI system in this extreme polyploid species and the alleles identified will be also useful for phylogenetic studies of Prunus S-RNases as the number of S-RNase sequences was limited in the Racemose group of Prunus (where P. laurocerasus belongs to).

[Dysphagiafelmérések akut stroke-ban]. / Akut stroke-betegeken validált ágy melletti dysphagiafelmérések az elmúlt húsz évben ­ szisztematikus irodalmi áttekintés.

BACKGROUND AND PURPOSE: Stroke associated dysphagia can have serious consequences such as aspiration pneumonia. The Hungarian guideline on nutritional therapy for stroke patients recommends dysphagia assessment, as early screening can optimize disease outcome and hospital cost. Thus far, this may be the first study in Hungarian that has documented a systematic review about the available validated dysphagia assessments of acute stroke. Purpose - The aim of this study was to summarize the instrumentally validated bedside dysphagia screening tools for acute stroke patients, which were published in the last twenty years. Our objective was to describe the characteristics of the validation studies, examine their study design, and sample the sub-tests and the diagnostic accuracy of the assessments. METHODS: A systematic research was carried out of the literature between 2001 and 2021 in eight scientific databases with search terms appropriate to our objectives. Subjects of the study - 652 articles were found and were reduced to eight. We made a comparative analysis of these. RESULTS: The GUSS test reached a high level of sensitivity compared to the others. In our study sample, the prevalence of instrumentally confirmed dysphagia among acute stroke patients was 56.1%. CONCLUSION: The focus and the composition of the analyzed studies differed and posed problems such as the ambiguity of the concept of dysphagia, the difference in outcome indicators, or the timing of screening. The GUSS test, which offers domestic management, is a suitable tool for the Hungarian clinical use.

A new method to determine the optimal orientation of Slim Modiolar cochlear implant electrode array insertion.

BACKGROUND AND PURPOSE: Our goal was to determine the optimal orientation of insertion of the Slim Modiolar electrode and develop an easy-to-use method to aid implantation surgery. In some instances, the electrode arrays cannot be inserted in their full length. This can lead to buckling, interscalar dislocation or tip fold-over. In our opinion, one of the possible reasons of tip fold-over is unfavourable orientation of the electrode array. Our goal was to determine the optimal orientation of the Slim Modiolar electrode array relative to clear surgical landmarks and present our method in one specified case. METHODS: For the measurement, we used the preoperative CT scan of one of our cochlear implant patients. These images were processed by an open source and free image visualization software: 3D Slicer. In the first step we marked the tip of the incus short process and then created the cochlear view. On this view we drew two straight lines: the first line represented the insertion guide of the cochlear implant and the second line was the orientation marker (winglet). We determined the angle enclosed by winglet and the line between the tip of the incus short process and the cross-section of previously created two lines. For the calculation we used a self-made python code. RESULTS: The result of our algorithm for the angle was 46.6055°. To validate this result, we segmented, from the CT scan, the auditory ossicles and the membranaceous labyrinth. From this segmentation we generated a 3D reconstruction. On the 3D view, we can see the position of the previous lines relative to the anatomical structures. After this we rotated the 3D model together with the lines so that the insertion guide forms a dot. In this view, the angle was measured with ImageJ and the result was 46.599°. CONCLUSION: We found that our method is easy, fast, and time-efficient. The surgery can be planned individually for each patient, based on their routine preoperative CT scan of the temporal bone, and the implantation procedure can be made safer. In the future we plan to use this method for all cochlear implantation surgeries, where the Slim Modiolar electrode is used.

Above-ground parts of white grapevine Vitis vinifera cv. Furmint share core members of the fungal microbiome.

Grapevine (Vitis vinifera) is a reservoir of fungal endophytes that may affect its growth, health status and grape production. Although there is growing interest in comparing fungal communities of mainly red grape varieties across various factors using only high-throughput sequencing, the small-scale mycobiome variations in geographically close vineyards need further examination. We aimed to characterize the fungal microbiome of the above-ground tissues of V. vinifera cv. Furmint in different plant parts, seasons and sites using culture-dependent and culture-independent methods, and in planta fluorescent microscopic visualization techniques. Samples were collected from four sites of the Tokaj wine region in Mád and two reference sites in Eger, Hungary, across different seasons for 2 years. Fungal endophytes of young and mature leaves, flowers and grape bunches were collected at different phenological stages. Based on each technique, Aureobasidium pullulans, Cladosporium spp. and the complex species Alternaria alternata dominated the community at every site, season and plant organ. We found no significant difference among communities in distinct neighbouring vineyards, nor when compared with the distant reference sites. We can conclude that the different shoot parts of the Furmint grapevines harbour a common core group of fungal community in these regions.

Christmas, acute ischemic stroke and stroke-related mortality in Hungary.

OBJECTIVES: Risk factors for stroke include psychological effects, such as depression. Festive occasions (such as Christmas in Hungary) may carry a significant emotional impact and may therefore contribute to increased cardiovascular risk. Thrombolytic treatment of acute ischemic stroke has a narrow time window and allows for the precise assessment of stroke incidence. MATERIALS & METHODS: We analyzed anonymized national data of the number of thrombolytic treatments for acute ischemic stroke and the number of stroke-related deaths between 1 January 2007 and 31 December 2016 in Hungary within 2-day, 5-day, and 1-month periods preceding and following 24 December each year. Analysis of subgroups based on age (below and over 65 years) and sex was also performed. RESULTS: The number of thrombolytic treatments was higher in all three periods preceding Christmas compared to the corresponding period that follows the feast. This increase was particularly prominent in men below 65 years of age. While overall stroke-associated mortality was increased 1 month after Christmas, the death rate was higher a month before rather than after Christmas in men below 65 years of age and in women both below and over 65 years of age 5 days before Christmas. CONCLUSIONS: These findings may predominantly relate to emotional and psychological factors. In case of women, the anxiety secondary to festive preparations, while in men below 65 years, the increased psychological stress of providing financial security for the celebration may play an important role.

[The first Hungarian patient with Guillain-Barre syndrome after COVID-19]. / Covid-19-asszociált Guillain­Barré-szindróma elsô hazai esete.

Guillain-Barré syndrome (GBS) is a sporadic, relatively rare disease. In serious cases, it can lead to respiratory failure and death. The correlation between SARS-CoV-2 and the risk of GBS is not yet known. COVID-19-associated prolonged pulmonary complications could be worsened by the potential airway interference caused by GBS. The literature is inconsistent whether SARS-CoV-2 virus has direct or indirect effect on the onset of GBS. The authors describe the medical history of the first published GBS patient in Hungary with a preceding confirmed COVID-19 infection. The trigger role of COVID-19 infection is assumed because of the subsequent development of GBS after COVID-19 infection. So far none of the patients in the literature (including this patient) had positive PCR of SARS-CoV-2 virus from the cerebrospinal fluid.

Interaction between elevated temperature and different types of Na-salicylate treatment in Brachypodium dystachion.

Salicylic acid (SA) plays a role in several physiological processes in plants. Exogenously applied SA is a promising tool to reduce stress sensitivity. However, the mode of action may depend on how the treatment was performed and environmental conditions may alter the effects of SA. In the present study the physiological and biochemical effects of different modes of application (soaking seeds prior sowing; spraying leaves with 0.5 mM NaSA) were compared at normal and moderately elevated temperatures (4 h; 35°C) in Brachypodium distachyon (L.) P. Beauv. plants. While soaking the seeds stimulated plant growth, spraying caused mild stress, as indicated by the chlorophyll-a fluorescence induction parameters and changes in certain protective compounds, such as glutathione, flavonoids or antioxidant enzymes. Elevated temperature also caused an increase in the glutathione-S-transferase activity, and this increase was more pronounced in plants pre-treated with NaSA. Both seed soaking or spraying with NaSA and exposure to heat treatment at 35°C reduced the abscisic acid levels in the leaves. In contrast to abscisic acid, the jasmonic acid level in the leaves were increased by both spraying and heat treatment. The present results suggest that different modes of application may induce different physiological processes, after which plants respond differently to heat treatment. Since these results were obtained with a model plants, further experiments are required to clarify how these changes occur in crop plants, especially in cereals.

Utilization of acute vascular imaging and neurointervention for acute ischaemic stroke patients in 20 Hungarian stroke centers.

BACKGROUND AND PURPOSE: Acute mortality rate of stroke in Hungary is significantly higher than in Western Europe, which is likely to be partially attributable to suboptimal treatment. METHODS: We examined the use of acute vascular imaging and mechanical thrombectomy for acute ischaemic stroke patients. We collected data on 20 consecutive patients from Hungarian stroke centers before 31st August 2016. RESULTS: Out of the reported 410 patients, 166 (40.4%) underwent CT angiography and 44 (10.7%) had mechanical thrombectomy. CONCLUSION: Only about 1/3 of acute ischaemic stroke patients eligible for thrombectomy actually had it. The underlying reasons include long onset-to-door time, low utilization of acute vessel imaging and a limited neuro-intervention capacity needing improvement.

The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells.

Several monoclonal antibodies and inhibitors targeting signalling pathways are being used in personalised medicine. Anti-EGFR antibodies seem to be effective, however, therapy resistance often occurs in colon carcinoma cases. mTOR inhibitors (mTORIs) could have a potential role in the breakthrough of therapy resistance. The mTOR activity related protein expression patterns and the in vitro effects of EGFR inhibitors (EGFRIs), mTORIs and their combinations were studied in different colon carcinoma cell lines (with different genetic backgrounds). Alamar Blue test and flow cytometry were used to analyse the in vitro proliferation and apoptotic effects of cetuximab, gefitinib, cisplatin, rapamycin, PP242 and NVP-BEZ235. The expressions of mTOR activity related proteins (p-70S6K, p-S6, Rictor, p-mTOR, Raptor) were studied by Western blot, immunocytochemistry and Duolink staining. The EGFRI resistance of the studied colon carcinoma cell lines related to their known mutations were confirmed, neither gefitinib nor cetuximab inhibited the proliferation or induced apoptosis in vitro. Individual differences in Rictor and Raptor expressions were detected by Western blot and immunocytochemistry beside elevated mTOR activity of these different colon carcinoma cell lines. These expression patterns correlated to the mTORIs sensitivity differences, moreover, mTORIs could enhance the effects of EGFRIs and other in vitro treatments. Our results suggest that mTORI combinations could be helpful in both EGFRI and platinum-based therapy of colon carcinomas. Moreover, we suggest determining both mTOR complex activity and mutations in Akt/mTOR signalling pathways for selecting the appropriate mTORIs and patients in potential future combination treatments.

Repeatability, reproducibility and interocular difference in the assessments of optic nerve OCT in children- a Swedish population-based study.

BACKGROUND: The aim was, first, to collect normative data of the optic nerve head and the peripapillary retinal nerve fibre layer (RNFL) thickness assessed with Cirrus SD-OCT, in healthy children in a population-based study; second, using these data, to examine repeatability, reproducibility and the interocular difference. METHODS: One-hundred and ten eyes from 57 children aged 6-15 born at term, were examined. Best-corrected visual acuity and refraction were assessed. Both eyes were examined and the interocular difference was calculated. Repeatability was calculated by one examiner performing three assessments. Thereafter, a second examiner repeated the assessments to calculate reproducibility. RESULTS: Mean RNFL thickness was 99.2 (SD 8.8) µm, mean disc area 1.89 (SD 0.37) mm2 and mean rim area 1.52 (SD 0.26) mm2. No significant correlations with age, gender or refraction were found. Repeatability and reproducibility were good overall. There was interocular symmetry between the eyes. CONCLUSIONS: Normal values for optic nerve head and RNFL thickness assessed with Cirrus SD-OCT were gathered to obtain a normal material in children. High repeatability and reproducibility indicated reliability of assessments performed by different examiners on different occasions. Overall, good correlation between right and left eyes was found.

Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm.

Importance: The function of rods and cones in children born extremely preterm has not yet been fully investigated. Objective: To compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term. Design, Setting, and Participants: A subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks' gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash. Main Outcomes and Measures: The ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined. Results: Adequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: mean difference, -48.9 µV [95% CI, -80.0 to -17.9 µV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: mean difference, -55.7 µV [95% CI, -92.5 to -18.8 µV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, -12.1 µV [95% CI, -22.5 to -1.6 µV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group. Conclusions and Relevance: Both rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.