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Clinical Neuroscience

NOVEMBER 30, 2020

[New results of neuroscience research – the background of symptomatological and etiological diversity of mental disorders]


[Nowadays, the focus of genetic, neurobiological, neuropsychological and psychosocial research is on a more accurate discovery of the etiology of mental illnesses, especially with regard to the role and complex interactions of certain risk factors. It is increasingly challenging to interpret the results of different aspects and methodologies in a coherent theoretical framework, as this can only lead to a more accurate understanding of the complexity and mechanism of the psychiatric disorders. The main aim of this paper to overview recent studies on etiological background of mental disorders and to present the most important aspects of the Research Domain Criteria (RDoC) system. Review of reports from comprehensive studies published in the most important psychiatric journals over the past five years summarizing new findings on the etio­logy of mental disorders. Although current classifications indicate that mental disorders are strictly distinct diagnostic categories, new findings suggest that these marked differences in symptomatic, genetic, and neurobiological backgrounds are not detectable, as many mental disorders have been identified as having common molecular genetic risk factors, which may indicate common neurobiological pathomechanisms. Research results support the need for a rethinking of psychiatric nosology on an etiological basis and represent an important step forward in the more accurate exploration of the neurobiological background factors of mental disorders and thus in the development of more targeted therapeutic approaches. The development of the RDoC system can be a great help in this, as this dimensional approach offers the possibility of integrating the - often diffuse or even contradictory - neuroscientific research findings into a unified theoretical framework for the etiology, nosology and treatment of mental disorders. ]

Clinical Neuroscience

SEPTEMBER 30, 2020

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Oncology

FEBRUARY 20, 2019

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Neuroscience

SEPTEMBER 30, 2019

[The role of Hungarian-rooted scholars in the development of Otoneurology ]

TAMÁS T. László, GARAI Tibor, TOMPOS Tamás, MAIHOUB Stefani, SZIRMAI Ágnes

[Despite of the symptoms of vertigo have been known since thousands of years, it was evident by the research of the pioneer scientists of the 19th century (Flourens, Ménière, Breuer and others) that dizziness can also be attributed to inner ear disfunctions. The discovery of the vestibulo-ocular reflex was an important milestone (Endre Hőgyes, 1884). The vestibulo-ocular reflex stabilizes images on the retina by rotating the eyes at the same speed but in the opposite direction of head motion. The milestone discovery of Hőgyes by stimulating individual labyrinth receptors and recording the activity of eye muscles were verified by János Szentágothai in 1950. Low-frequency lesions of the angular vestibulo-ocular reflex can be investigated by caloric test (Robert Bárány,1906), high-frequency lesions by head impulse test (Gabor Michael Halmagyi and Ian Stewart Curthoys, 1988).]

Clinical Neuroscience

MARCH 30, 2019

EEG-based connectivity in patients with partial seizures with and without generalization

DÖMÖTÖR Johanna, CLEMENS Béla, EMRI Miklós, PUSKÁS Szilvia, FEKETE István

Objective - to investigate the neurophysiological basis of secondary generalization of partial epileptic seizures. Patients and methods - inter-ictal, resting-state EEG functional connectivity (EEGfC) was evaluated and compared: patients with exclusively simple partial seizures (sp group) were compared to patients with simple partial and secondary generalized seizures (spsg group); patients with exclusively complex partial seizures (cp group) were compared to patients with cp and secondary generalized seizures (cpsg group); the collapsed sp+cp group (spcp) was compared to those who had exclusively secondary generalized seizures (sg group). EEGfC was computed from 21-channel waking EEG. 3 minutes of waking EEG background activity was analyzed by the LORETA Source Correlation (LSC) software. Current source density time series were computed for 23 pre-defined cortical regions (ROI) in each hemisphere, for the 1-25 Hz very narrow bands (1 Hz bandwidth). Thereafter Pearson correlation coefficients were calculated between all pairs of ROI time series in the same hemisphere. Z-scored correlation coefficients were compared at the group level (t-tests and correction for multiple comparisons by local false discovery rate, FDR). Results - Statistically significant (corrected p<0.05) EEGfC differences emerged at specific frequencies (spsg > sg; cpsg > cp), and at many frequencies (sg > spcp). The findings indicated increased coupling between motor cortices and several non-motor areas in patients with partial and sg seizures as compared to patients with partial seizures and no sg seizures. Further findings suggested increased coupling between medial parietal-occipital areas (structural core of the cortex) and lateral hemispheric areas. Conclusion - increased inter-ictal EEGfC is associated with habitual occurrence of secondary generalized seizures.

Lege Artis Medicinae

AUGUST 30, 2018

[How to diagnose idiopathic pulmonary fibrosis. Part 2]


[Idiopathic pulmonary fibrosis is a severe irreversible lung disease with a progressive course. The disease onset is hard to discover due to the unspecific signs and symp­toms. It occurs mainly in elderly people. In the past decades its prevalence has increased continuously. Physical examination, restrictive pattern on lung function test with decreased diffusion capacity are characteristic features of the disease. Chest X-ray showing fibrotic pattern also points toward the diagnosis of idiopathic pulmonary fibrosis. Differential diagnosis is based on high resolution komputertomográfy. Diag­nosis of IPF is based on the appearance of usual interstitial pneumonia pattern together with the lack of external risk factors and autoimmune or other diseases also known to cause this pattern seen on chest imaging. If no firm diagnosis can be built lung biopsy is required. Multidis­ciplinary teams from clinician, radiologist and pathologist are set in predefined centres that could provide care with novel antifibrotic drugs. These can slow disease progression and are in the frontline in the treatment of the disease. Further research is required to understand the pathomechanism and foster the discovery of further treatment options. ]

Clinical Oncology

FEBRUARY 10, 2017

[Diffuse large B-cell lymphoma – a road to personal therapy]


[The majority of patients with diffuse large B-cell lymphoma can be cured using the standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) based therapy. However, approximately 30-40% of the patients are refractory to the therapy or they relapse. The currently available salvage therapies represent a realistic curative approach only for approximately one quarter of the patients. Therefore, there is unmet clinical need for more effi cient fi rst line and salvage therapies in DLBCL. The rapid advances in the fi eld of molecular genetic techniques lead to a better understanding of the biological heterogeneity as well as the discovery of the key factors involved in the pathogenesis of the disease. Nowadays, the distinction between the cases with germinal center B-cell and activated B-cell origin characterized with different prognosis has therapeutic implications. Presently, the therapy of the so-called double-hit lymphomas also represents an unmet clinical need. The next generation sequencing based studies lead to the discovery of novel molecular targets, including components of different cellular signaling pathways, immune checkpoints and components of the microenvironment. Targeted therapies against many of these molecular targets are being tested in different clinical trials. Due the heterogeneity of the disease, it is of critical importance to identify those patient groups who will benefi t from a particular targeted therapy. Hopefully, this risk-adopted therapeutic approach will become soon available for patients with DLBCL. Currently, the R-CHOP therapy still represents the gold standard in treatment of patients with DLBCL.]

Clinical Neuroscience

MARCH 30, 2017

[Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia]

PULAY Attila József, KOLLER Júlia, NAGY László, MOLNÁR Mária Judit, RÉTHELYI János

[Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives - The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multilocus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods - Associations of single nucleotide and indel markers were transferred to gene- and geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results - After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xq13 cytobands were found (p_corr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (P_rep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses. ]

Hypertension and nephrology

OCTOBER 20, 2016

[A new perspective on the extrarenal regulation of sodium and water balance]

AGÓCS Róbert István, SUGÁR Dániel, SULYOK Endre, SZABÓ J. Attila

[The regulation of the homeostasis of sodium and water is one of the oldest fields in medical research. Our article exhibits a new aspect of sodium balance: the concept of the regulated sodium storage taking place in the interstitium of the skin. We summarize the history of the research carried out in this area, beginning with the discovery of osmotically inactive sodium reservoirs to the localization of these buffers and the elucidation of the role of a regulating cutaneous cascade, which has an effect on blood pressure. Glycosaminoglycan (GAG) macromolecules present in the skin interstitium, come into reversible contact with the excess of dietary sodium intake. Thus in addition to the known role of the kidney, the above system may contribute to the regulation of sodium- and water balance and thereby to the regulation of blood pressure.]

Lege Artis Medicinae

JUNE 20, 2016

[Current topics in modern health informatics]


[Development in technology - significant improvement in calculatory and storage capacities of computers - enable such calculation- and data-intensive applications, which were merely theoretical possibilities, even just a decade ago. Selected fields and methods of medical informatics are discussed in the article. Informatics methods became by now essential to biomedical research, drug discovery and development, and healthcare. Furthermore, the article presents a modern mobile information source application, developed in Hungary, which is aimed at supporting the activities and know-how of professionals in drug development and clinical research.]