Correction: Time of day is associated with paradoxical reductions in global signal fluctuation and functional connectivity.

[This corrects the article DOI: 10.1371/journal.pbio.3000602.].

Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity.

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local-global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Yan2023_homotopic).

Time of day is associated with paradoxical reductions in global signal fluctuation and functional connectivity.

The brain exhibits substantial diurnal variation in physiology and function, but neuroscience studies rarely report or consider the effects of time of day. Here, we examined variation in resting-state functional MRI (fMRI) in around 900 individuals scanned between 8 AM and 10 PM on two different days. Multiple studies across animals and humans have demonstrated that the brain's global signal (GS) amplitude (henceforth referred to as "fluctuation") increases with decreased arousal. Thus, in accord with known circadian variation in arousal, we hypothesised that GS fluctuation would be lowest in the morning, increase in the midafternoon, and dip in the early evening. Instead, we observed a cumulative decrease in GS fluctuation as the day progressed. Although respiratory variation also decreased with time of day, control analyses suggested that this did not account for the reduction in GS fluctuation. Finally, time of day was associated with marked decreases in resting-state functional connectivity across the whole brain. The magnitude of decrease was significantly stronger than associations between functional connectivity and behaviour (e.g., fluid intelligence). These findings reveal time of day effects on global brain activity that are not easily explained by expected arousal state or physiological artefacts. We conclude by discussing potential mechanisms for the observed diurnal variation in resting brain activity and the importance of accounting for time of day in future studies.

Individual-Specific Areal-Level Parcellations Improve Functional Connectivity Prediction of Behavior.

Resting-state functional magnetic resonance imaging (rs-fMRI) allows estimation of individual-specific cortical parcellations. We have previously developed a multi-session hierarchical Bayesian model (MS-HBM) for estimating high-quality individual-specific network-level parcellations. Here, we extend the model to estimate individual-specific areal-level parcellations. While network-level parcellations comprise spatially distributed networks spanning the cortex, the consensus is that areal-level parcels should be spatially localized, that is, should not span multiple lobes. There is disagreement about whether areal-level parcels should be strictly contiguous or comprise multiple noncontiguous components; therefore, we considered three areal-level MS-HBM variants spanning these range of possibilities. Individual-specific MS-HBM parcellations estimated using 10 min of data generalized better than other approaches using 150 min of data to out-of-sample rs-fMRI and task-fMRI from the same individuals. Resting-state functional connectivity derived from MS-HBM parcellations also achieved the best behavioral prediction performance. Among the three MS-HBM variants, the strictly contiguous MS-HBM exhibited the best resting-state homogeneity and most uniform within-parcel task activation. In terms of behavioral prediction, the gradient-infused MS-HBM was numerically the best, but differences among MS-HBM variants were not statistically significant. Overall, these results suggest that areal-level MS-HBMs can capture behaviorally meaningful individual-specific parcellation features beyond group-level parcellations. Multi-resolution trained models and parcellations are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Kong2022_ArealMSHBM).

Spatial Topography of Individual-Specific Cortical Networks Predicts Human Cognition, Personality, and Emotion.

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 min) showed comparable generalizability as parcellations estimated by 2 state-of-the-art methods using 5 sessions (50 min). We also showed that behavioral phenotypes across cognition, personality, and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.

Global signal regression strengthens association between resting-state functional connectivity and behavior.

Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functional connectivity fingerprinting, here we considered the utilitarian question of whether GSR strengthens or weakens associations between resting-state functional connectivity (RSFC) and multiple behavioral measures across cognition, personality and emotion. By applying the variance component model to the Brain Genomics Superstruct Project (GSP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 47% across 23 behavioral measures after GSR. In the Human Connectome Project (HCP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 40% across 58 behavioral measures, when GSR was applied after ICA-FIX de-noising. To ensure generalizability, we repeated our analyses using kernel regression. GSR improved behavioral prediction accuracies by an average of 64% and 12% in the GSP and HCP datasets respectively. Importantly, the results were consistent across methods. A behavioral measure with greater RSFC-explained variance (using the variance component model) also exhibited greater prediction accuracy (using kernel regression). A behavioral measure with greater improvement in behavioral variance explained after GSR (using the variance component model) also enjoyed greater improvement in prediction accuracy after GSR (using kernel regression). Furthermore, GSR appeared to benefit task performance measures more than self-reported measures. Since GSR was more effective at removing motion-related and respiratory-related artifacts, GSR-related increases in variance explained and prediction accuracies were unlikely the result of motion-related or respiratory-related artifacts. However, it is worth emphasizing that the current study focused on whole-brain RSFC, so it remains unclear whether GSR improves RSFC-behavioral associations for specific connections or networks. Overall, our results suggest that at least in the case for young healthy adults, GSR strengthens the associations between RSFC and most (although not all) behavioral measures. Code for the variance component model and ridge regression can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/Li2019_GSR.

Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and polysubstance-dependent individuals.

Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance-dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened 'top-down' control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no-go (GNG) task, we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent polysubstance-dependent (poly-SUD) individuals and controls during a randomised double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly-SUD groups respectively. Self-reported trait impulsivity in the poly-SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly-SUD groups, which are predicted by trait impulsivity in the poly-SUD group.

Neural correlates of the LSD experience revealed by multimodal neuroimaging.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life-a case study.

BACKGROUND: The perinatal period carries the highest risk for stroke in childhood; however, the pathophysiology is poorly understood and preventive, prognostic, and therapeutic strategies are not available. A new pathophysiological model describes the development of neonatal arterial ischemic stroke (NAIS) as the combined result of prenatal inflammation and hypoxic-ischemic insult. Neuroinflammation and a systemic inflammatory response are also important features of NAIS. Identifying key players of the inflammatory system is in the limelight of current research. CASE PRESENTATION: We present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from the first month of life. All neonates were admitted with the initial diagnosis of hypoxic ischemic encephalopathy (HIE); however, early MRI examination revealed NAIS. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Peripheral blood mononuclear cells were assessed with flow cytometry and plasma cytokine levels were measured. Pooled data from the cohort of four NAIS patients were compared to infants with HIE. At 6 and 72 h of age, the prevalence of IL10+ CD8+ lymphocytes remained lower in NAIS. At 6 h, CD8+ lymphocytes in NAIS produced more IL-17. At 72 h, CD8+ cells produced more IL-6 in severe HIE than in NAIS, but IL-6 production remained elevated in CD8 cells at 1 month in NAIS, while it decreased in HIE. At 1 week, the prevalence of TGF-ß + lymphocytes prone to enter the CNS was elevated in NAIS. On the other hand, by 1 month of age, the prevalence of TGF-ß + CD4+ lymphocytes decreased in NAIS compared to HIE. At 72 h, we found elevated plasma levels of IL-5, MCP-1, and IL-17 in NAIS. By 1 month, plasma levels of IL-4, IL-12, and IL-17 decreased in NAIS but remained elevated in HIE. CONCLUSIONS: Differences in the cytokine network are present between NAIS and HIE. CD8 lymphocytes appear to shift towards the pro-inflammatory direction in NAIS. The inflammatory response appears to be more pronounced at 72 h in NAIS but decreases faster, reaching lower plasma levels of inflammatory markers at 1 month.

Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study.

BACKGROUND: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. METHODS: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Neonates were divided into a moderate (n = 17) and a severe (n = 11) group based on neuroradiological and amplitude-integrated EEG characteristics. Peripheral blood mononuclear cells were assessed with flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Components of the kynurenine pathway were assessed by high-performance liquid chromatography. RESULTS: The prevalence and extravasation of IL-1b + CD4 cells were higher in severe than in moderate asphyxia at 6 h. Based on Receiver operator curve analysis, the assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia. Intracellular levels of TNF-α in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-α were higher in the severe group. Plasma IL-6 levels were higher at 1 week in the severe group and decreased by 1 month in the moderate group. Intracellular levels of IL-6 peaked at 24 h in both groups. Intracellular TGF-ß levels were increased from 24 h onwards in the moderate group. CONCLUSIONS: IL-1ß and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-α seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.

Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task.

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards. Naltrexone is currently licensed for alcohol and opiate dependence, and may remediate such disturbances through the blockade of MORs in fronto-striatal reward circuitry. Therefore, we examined the potential acute modulating effects of naltrexone on the anticipation of, and instrumental responding for, non-drug rewards in long-term abstinent alcoholics, alcoholic poly substance-dependent individuals and controls using a monetary incentive delay (MID) task during a randomized double blind placebo controlled functional MRI study. We report that the alcoholic poly substance-dependent group exhibited slower and less accurate instrumental responding compared to alcoholics and controls that was less evident after acute naltrexone treatment. However, naltrexone treatment was unable to remediate disturbances within fronto-striatal regions during reward anticipation and 'missed' rewards in either substance-dependent group. While we have not been able to identify the underlying neural mechanisms for improvement observed with naltrexone in the alcoholic poly-substance dependent group, we can confirm that both substance-dependent groups exhibit substantial neural deficits during an MID task, despite being in long-term abstinence.

Folic acid content and antioxidant activity of different types of beers available in Hungarian retail.

In this study 40 Hungarian retail beers were evaluated for folic acid content, antioxidant profile and physicochemical parameters. The physicochemical parameters, folic acid content and antioxidant activity of alcohol-free beers were the lowest. Folic acid content of beers aged with sour cherries showed high values, more than 0.4 mg/l and an alcohol-free beer-based mixed drink made with lemon juice contained more than 0.2 mg/l of folic acid. Dark beers and beers aged with sour cherries had the highest antioxidant activity probably owing to their high extract content, components released from the fruits and special malts. These results highlight the possibility of achieving adequate folic acid and relevant antioxidant intake without excessive alcohol and energy consumption by selecting appropriate beer types.

LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion.

The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp 37:3031-3040, 2016. © 2016 Wiley Periodicals, Inc.

Real time kinetic flow cytometry measurements of cellular parameter changes evoked by nanosecond pulsed electric field.

Nanosecond pulsed electric field (nsPEF) is a novel method to increase cell proliferation rate. The phenomenon is based on the microporation of cellular organelles and membranes. However, we have limited information on the effects of nsPEF on cell physiology. Several studies have attempted to describe the effects of this process, however no real time measurements have been conducted to date. In this study we designed a model system which allows the measurement of cellular processes before, during and after nsPEF treatment in real time. The system employs a Vabrema Mitoplicator(TM) nsPEF field generating instrument connected to a BD Accuri C6 cytometer with a silicon tube led through a peristaltic pump. This model system was applied to observe the effects of nsPEF in mammalian C6 glioblastoma (C6 glioma) and HEK-293 cell lines. Viability (using DRAQ7 dye), intracellular calcium levels (using Fluo-4 dye) and scatter characteristics were measured in a kinetic manner. Data were analyzed using the FACSKin software. The viability and morphology of the investigated cells was not altered upon nsPEF treatment. The response of HEK-293 cells to ionomycin as positive control was significantly lower in the nsPEF treated samples compared to non-treated cells. This difference was not observed in C6 cells. FSC and SSC values were not altered significantly by the nsPEF treatment. Our results indicate that this model system is capable of reliably investigating the effects of nsPEF on cellular processes in real time. © 2016 International Society for Advancement of Cytometry.

[Proctocolectomy with J pouch. Ileo-anal anastomosis performed with PPH stapler. Our experiences after 88 cases]. / J-pouchcsal rekonstruált proctocolectomia során PPH-géppel készített ileoanalis anastomosis. Tapasztalataink 88 eset kapcsán.

AIM: Ulcerative colitis (CU) or Familiar Polyposis (FAP) can be the indication for proctocolectomy reconstructed with J pouch. The complete removal of the colon mucosa is essential regarding the late complications and at the same time the atraumatic surgical technique is very important concerning on the long term functional results. Both aspects seems to be answered by the stapled ileo-anal anastomosis using a "procedure for prolaps and haemorrhoids (PPH)" stapler applied by us since 2000. PATIENTS AND METHODS: 117 proctocolectomies reconstructed with J pouch and ileo-anal anastomosis were performed in our department between March 1990 and September 2016 indicated by CU or by FAP. In the first time period the ileo-anal anastomosis was sutured by hand (29 cases) and since 2000 the PPH stapler was applied as a routine (88 patients). Deviating ileostomy was performed in most cases of us. The data of the 117 patients were collected from the database of our hospital, 45 of them were interviewed personally and another 31 patients were contacted by phone, so 76 patients (65%) were eligible for follow-up. Frequency of stool, use of loperamid, level of incontinence (Wexner score) and perianal dermatitis were detected. The mean follow-up time was 18.6 years in the hand-sewn anastomosis group and 7.6 years in the PPH group. RESULTS: In the hand-sewn anastomosis group in 4/29 cases (13.8%) the removal of the pouch with definite ileostomy were necessary (2 pouchitis, 1 pouch necrosis, 1 recidiv rectum cancer); the mean stool frequency was 4.3 per day; the Wexner incontinence score was 8.5 and 2/15 patients (13.3%) live with ileostomy caused by incontinence. In the PPH stapled ileo-anal anastomosis group in 4/88 cases (4.5%) were the pouch removed (caused by pouchitis), the mean stool frequency was 4.0 per day; the Wexner score was 7.6 and 4/61 patients (6.6%) live with ileostomy caused by incontinence. CONCLUSIONS: Based on our experience the ileo-anal anastomosis performed by PPH stapler is technically feasible, seems to be effective concerning on the complete removal of the rectal mucosa and we observed better functional results compared with the hand-sewn anastomosis. Our data should be confirmed because of the low patients' volume.

[Minimal invasive esophageal resection with anastomosis on the neck [McKeown]. Our experiences after 20 cases]. / Minimálisan invazív oesophagusreszekció nyaki anastomosissal (McKeown-mutét). Tapasztalataink 20 eset kapcsán.

OBJECTIVE: Esophageal resection is a traumatic intervention usually performed on patients with poor condition, resulting high mortality and morbidity. To improve the high incidence of complications, minimal invasive interventions were introduced. The results of the thoracoscopically and laparoscopically performed esophageal resection (McKeown) was investigated after 20 cases and the technical details of the surgical intervention are presented. PATIENTS AND METHOD: 20 thoracoscopic esophageal resection with laparoscopic gastric tube formation (sec. Akiyama) preparing the esophago-gastric anastomosis on the neck were performed in our department in the last four years. 1 patient with stricture and the other 19 patients with esophageal cancer were operated on, among them11 had T4 stage. 17 patient received neoadjuvant chemo-radiotherapy because of advanced disease. Regular follow up examinations were performed in the oncological outpatient department. RESULTS: 8 patients are alive after a mean follow up period of 25 months, 2 of them are treated oncologically because of recurrent disease. 19 patients were extubated within 12 hours after the intervention and the time spent in the intensive care unit were reduced to 1 or 2 days. The mean duration of the intervention was 320 minutes. Thoracoscopic dissection was performed in 8 patients without ventilation of the right lung using double lumen tracheal tube, among them 3 patients developed pneumonia in the postoperative period. The remaining 12 patients were operated with ventilated right lung, among them one patient developed pneumonia. One patient was converted because of injury of the thoracic aorta, after urgent thoracotomy we managed to suture the aortic wall. 1 patient died in 30 days after the operation, caused by leakage of the anastomosis, resulting mediastinitis and esophago-tracheal fistula. In two patients re-thoracoscopy and ligation of the thoracic duct was performed because of chylothorax refractory for conservative treatment. CONCLUSIONS: According to our observation the minimal invasive esophageal resection resulted in comparable oncological results with relevant reduction of mortality and morbidity compared to the open procedure. After procedures performed with ventilated lung further reduction of pulmonary complication was found. In case of tumors infiltrating the tracheal or the aortic wall, thoracotomy should be considered to explore the thoracic cavity and to carry out the dissection, if it is possible. Our results should be reinforced because of low number of patients.

[Our metabolic surgical activity, 2010-2016]. / Metabolikus sebészeti tevékenységünk, 2010­2016.

INTRODUCTION: The prevalence of morbid obesity and its co-morbidities - first of all diabetes type 2 - increased dramatically in the last decades. As the conservative ways of treatment (diet, training, etc.) in most cases does not lead to effective and long term weight loss, there is an increasing need for the metabolic surgical interventions. METHOD: During the last 6 and half years 514 laparoscopic RouxY gastric bypass (LRYGB) and 54 laparoscopic gastric sleeve resection (LGSR) were performed in our department. The data of random selected 40 patients after primary LRYGB and 15 patients after sleeve resection were collected. The applied criteria of the indication for surgery, the routine examinations and treatments before and after the intervention, the results and the type and the rate of the complications will be presented. RESULTS: According to our experience both procedures are long term effective for weight loss and for the resolution of co-morbidities, and can be performed with low risk of complications. After LRYGB more effective weight loss (extra weight loss 88% vs. 68%) and higher rate of resolution of diabetes type 2, hypertension and gastro-esophageal reflux were found compared to sleeve resection. CONCLUSION: Based on our results we prefer LRYGB. Gastric sleeve resection is indicated by us, when there is no way - or only with high risk - to perform gastric bypass, taking into consideration of course the individual requirements of the patients.

Different calcium influx characteristics upon Kv1.3 and IKCa1 potassium channel inhibition in T helper subsets.

Functional imbalance between T helper subsets plays important role in the pathogenesis of autoimmune disorders. Transient increase of cytoplasmic calcium level, and sustention of negative membrane potential by voltage sensitive Kv1.3 and calcium-dependent IKCa1 potassium channels are essential for short-term lymphocyte activation, thus present possible target for selective immunomodulation. We aimed to investigate calcium influx sensitivity to the inhibition of potassium channels in the main T helper subsets. Peripheral blood from 11 healthy individuals was drawn and calcium influx kinetics following activation with phytohemagglutinin in Th1, Th2, Th17, and Treg cells were evaluated. Alteration of calcium influx induced by specific inhibitors of Kv1.3 and IKCa1 potassium channels, and the expression of Kv1.3 channels were also assessed. Highest cytoplasmic calcium concentration was observed in stimulated Th1 cells, while the lowest level was measured in Treg cells. In Th1 and Th17 cells, inhibition of both investigated potassium channels decreased calcium influx. In Th2 cells only the inhibitor of Kv1.3 channels, while in Treg cells none of the inhibitors had significant effect. Upon the inhibition of IKCa1 channels, short-term activation of proinflammatory cells was specifically decreased without affecting anti-inflammatory subsets, indicating that selective immunomodulation is possible in healthy individuals.