@article{MTMT:33219396, title = {Structural synaptic signatures of Alzheimer's disease and dementia with Lewy bodies in the male brain}, url = {https://m2.mtmt.hu/api/publication/33219396}, author = {Glebov, Oleg O. and Williamson, David and Owen, Dylan M. and Hortobágyi, Tibor and Troakes, Claire and Aarsland, Dag}, doi = {10.1111/nan.12852}, journal-iso = {NEUROPATH APPL NEURO}, journal = {NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY}, volume = {49}, unique-id = {33219396}, issn = {0305-1846}, year = {2023}, eissn = {1365-2990}, orcid-numbers = {Hortobágyi, Tibor/0000-0001-5732-7942} } @article{MTMT:33586582, title = {ABO blood group type and the risk of venous thromboembolism: the impact of interactions}, url = {https://m2.mtmt.hu/api/publication/33586582}, author = {Bagoly, Zsuzsa}, doi = {10.20452/pamw.16378}, journal-iso = {POL ARCH MED WEWN}, journal = {POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE}, volume = {132}, unique-id = {33586582}, issn = {0032-3772}, year = {2022}, eissn = {1897-9483}, pages = {1-2}, orcid-numbers = {Bagoly, Zsuzsa/0000-0001-5314-5607} } @article{MTMT:33251894, title = {The Correlation between Two Angiotensin-Converting Enzyme Inhibitor’s Concentrations and Cognition}, url = {https://m2.mtmt.hu/api/publication/33251894}, author = {Nagy, Attila Csaba and Majer, Réka and Csikai, Enikő and Dobos, Adrienn and Süvegh, Gábor and Csiba, László}, doi = {10.3390/ijerph192114375}, journal-iso = {INT J ENV RES PUB HE}, journal = {INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, volume = {19}, unique-id = {33251894}, issn = {1661-7827}, abstract = {Both lisinopril and enalapril are angiotensin-converting enzyme (ACE) drugs and widely used in the treatment of hypertension. Enalapril does not cross the blood–brain barrier, but lisinopril is centrally active. Our goal was to find out if there was a link between the actual concentration of ACE inhibitors and cognition and if there was a detectable difference between the two types of ACE inhibitors. Asymptomatic, non-treated patients were diagnosed by screening and the hypertension was confirmed by ambulatory blood pressure monitoring (ABPM). A battery of cognitive tests was used to assess the impact of randomly assigning participants to receive either lisinopril or enalapril. All neurocognitive functions were measured, especially the most affected by conditions of compromised perfusion pressures, such as hypertension, which are attention and executive functions. The lisinopril concentration showed a significant inverse correlation with mosaic test (coeff. = −0.5779) and seemed to have a significant negative effect on perceptual motor skills (coeff. = −0.5779), complex attention (coeff. = −0.5104) and learning (coeff. = −0.5202). Compared with enalapril, lisinopril is less successful in improving the components of cognitive functions.}, year = {2022}, eissn = {1660-4601}, orcid-numbers = {Nagy, Attila Csaba/0000-0002-0554-7350} } @article{MTMT:33216546, title = {Cysteine string protein alpha accumulates with early pre-synaptic dysfunction in Alzheimer’s disease}, url = {https://m2.mtmt.hu/api/publication/33216546}, author = {Rupawala, Huzefa and Shah, Keshvi and Davies, Caitlin and Rose, Jamie and Colom-Cadena, Marti and Peng, Xianhui and Granat, Lucy and Aljuhani, Manal and Mizuno, Keiko and Troakes, Claire and Perez-Nievas, Beatriz Gomez and Morgan, Alan and So, Po-Wah and Hortobágyi, Tibor and Spires-Jones, Tara L and Noble, Wendy and Giese, Karl Peter}, doi = {10.1093/braincomms/fcac192}, journal-iso = {BRAIN COMMUN}, journal = {BRAIN COMMUNICATIONS}, volume = {4}, unique-id = {33216546}, abstract = {In Alzheimer’s disease, synapse loss causes memory and cognitive impairment. However, the mechanisms underlying synaptic degeneration in Alzheimer’s disease are not well understood. In the hippocampus, alterations in the level of cysteine string protein alpha, a molecular co-chaperone at the pre-synaptic terminal, occur prior to reductions in synaptophysin, suggesting that it is a very sensitive marker of synapse degeneration in Alzheimer’s. Here, we identify putative extracellular accumulations of cysteine string alpha protein, which are proximal to beta-amyloid deposits in post-mortem human Alzheimer’s brain and in the brain of a transgenic mouse model of Alzheimer’s disease. Cysteine string protein alpha, at least some of which is phosphorylated at serine 10, accumulates near the core of beta-amyloid deposits and does not co-localize with hyperphosphorylated tau, dystrophic neurites or glial cells. Using super-resolution microscopy and array tomography, cysteine string protein alpha was found to accumulate to a greater extent than other pre-synaptic proteins and at a comparatively great distance from the plaque core. This indicates that cysteine string protein alpha is most sensitive to being released from pre-synapses at low concentrations of beta-amyloid oligomers. Cysteine string protein alpha accumulations were also evident in other neurodegenerative diseases, including some fronto-temporal lobar dementias and Lewy body diseases, but only in the presence of amyloid plaques. Our findings are consistent with suggestions that pre-synapses are affected early in Alzheimer’s disease, and they demonstrate that cysteine string protein alpha is a more sensitive marker for early pre-synaptic dysfunction than traditional synaptic markers. We suggest that cysteine string protein alpha should be used as a pathological marker for early synaptic disruption caused by beta-amyloid.}, year = {2022}, eissn = {2632-1297}, orcid-numbers = {Rupawala, Huzefa/0000-0001-6462-4339; Davies, Caitlin/0000-0003-2422-0633; So, Po-Wah/0000-0003-3449-8532; Hortobágyi, Tibor/0000-0001-5732-7942; Spires-Jones, Tara L/0000-0003-2530-0598; Noble, Wendy/0000-0002-7898-4295; Giese, Karl Peter/0000-0003-4503-7344} } @article{MTMT:33060272, title = {Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.}, url = {https://m2.mtmt.hu/api/publication/33060272}, author = {Ariëns, Robert A and Hunt, Beverley J and Agbani, Ejaife O and Ahnström, Josefin and Ahrends, Robert and Alikhan, Raza and Assinger, Alice and Bagoly, Zsuzsa and Balduini, Alessandra and Barbon, Elena and Barrett, Christopher D and Batty, Paul and Carneiro, Jorge David Aivazoglou and Chan, Wee Shian and de Maat, Moniek and de Wit, Kerstin and Denis, Cécile and Ellis, Martin H and Eslick, Renee and Fu, Hongxia and Hayward, Catherine P M and Ho-Tin-Noé, Benoit and Klok, Frederikus A and Kumar, Riten and Leiderman, Karin and Litvinov, Rustem I and Mackman, Nigel and McQuilten, Zoe and Neal, Matthew D and Parker, William A E and Preston, Roger J S and Rayes, Julie and Rezaie, Alireza R and Roberts, Lara N and Rocca, Bianca and Shapiro, Susan and Siegal, Deborah M and Sousa, Lirlândia P and Suzuki-Inoue, Katsue and Zafar, Tahira and Zhou, Jiaxi}, doi = {10.1002/rth2.12747}, journal-iso = {Res Pract Thromb Haemost}, journal = {RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS}, volume = {6}, unique-id = {33060272}, abstract = {The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas.}, year = {2022}, eissn = {2475-0379}, pages = {e12747}, orcid-numbers = {Bagoly, Zsuzsa/0000-0001-5314-5607} } @article{MTMT:33060167, title = {High Neutrophil-Lymphocyte Ratio and Low Lymphocyte-Monocyte Ratio Combination after Thrombolysis Is a Potential Predictor of Poor Functional Outcome of Acute Ischemic Stroke.}, url = {https://m2.mtmt.hu/api/publication/33060167}, author = {Sadeghi, Farzaneh and Sarkady, Ferenc and Zsóri, Katalin S and Szegedi, István and Orbán-Kálmándi, Rita Angéla and Székely, Edina G and Vasas, Nikolett and Berényi, Ervin and Csiba, László and Bagoly, Zsuzsa and Shemirani, Amir Houshang}, doi = {10.3390/jpm12081221}, journal-iso = {J PERS MED}, journal = {JOURNAL OF PERSONALIZED MEDICINE}, volume = {12}, unique-id = {33060167}, abstract = {(1) Background: Ischemic stroke is one of the leading causes of death and disability. An inflammatory response is observed in multiple stages of cerebral ischemia, particularly in the acute phase. Recent publications revealed that the neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) may be used to predict long-term prognosis in acute ischemic stroke (AIS) after thrombolysis. To test whether there is a relationship between the combination of these parameters and long-term prognosis, we analyzed the NLR-LMR combination in AIS patients treated with intravenous recombinant tissue plasminogen activator (rtPA); (2) Methods: The study included 285 adults with a diagnosis of AIS and rtPA treatment within a 4.5 h time window. Blood samples were obtained at admission and 24 h after thrombolysis to calculate pre- and post-thrombolysis NLR and LMR. Clinical data, including NIHSS was registered on admission and day 1. The long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). Therapy-associated intracranial hemorrhage (ICH) was classified according to ECASS II. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs of NLR and LMR as predictors of therapy outcomes; (3) Results: Patients were stratified by cutoffs of 5.73 for NLR and 2.08 for LMR. The multivariate logistic regression model, including all possible confounders, displayed no significant association between NLR or LMR with 3-months functional prognosis. The combination of high NLR-low LMR vs. low NRL-high LMR as obtained 24 h after thrombolysis was found to be an independent predictor of poor 3-months functional outcome (mRS ≥ 2; OR 3.407, 95% CI 1.449 to 8.011, p = 0.005). The proportion of patients between low NLR-high LMR and high NLR-low LMR groups from admission to day 1 showed no significant change in the good outcome group. On the other hand, in the poor outcome group (mRS ≥ 2), low NLR-high LMR and high NLR-low LMR groups displayed a significant shift in patient proportions from 67% and 21% at admission (p = 0.001) to 36% and 49% at 24 h after thrombolysis (p < 0.001), respectively; (4) Conclusions: Our study demonstrated for the first time that a high NLR-low LMR combination as observed at 24 h after thrombolysis can serve as an independent predictor of 3-months poor outcome in AIS patients. This simple and readily available data may help clinicians to improve the prognostic estimation of patients and may provide guidance in selecting patients for personalized and intensified care post-thrombolysis.}, keywords = {thrombolysis; ischemic stroke; Neutrophil-lymphocyte ratio; Lymphocyte-monocyte ratio}, year = {2022}, eissn = {2075-4426}, orcid-numbers = {Szegedi, István/0000-0003-4181-4361; Orbán-Kálmándi, Rita Angéla/0000-0002-2155-8279; Bagoly, Zsuzsa/0000-0001-5314-5607} } @article{MTMT:33060054, title = {Low α2-Plasmin Inhibitor Antigen Levels on Admission Are Associated With More Severe Stroke and Unfavorable Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis.}, url = {https://m2.mtmt.hu/api/publication/33060054}, author = {Székely, Edina Gabriella and Orbán-Kálmándi, Rita Angéla and Szegedi, István and Katona, Éva and Baráth, Barbara and Czuriga-Kovács, Katalin Réka and Lóczi, Linda and Vasas, Nikolett and Fekete, István and Fekete, Klára and Berényi, Ervin and Oláh, László and Csiba, László and Bagoly, Zsuzsa}, doi = {10.3389/fcvm.2022.901286}, journal-iso = {FRONT CARDIOVASC MED}, journal = {FRONTIERS IN CARDIOVASCULAR MEDICINE}, volume = {9}, unique-id = {33060054}, issn = {2297-055X}, abstract = {Intravenous administration of recombinant tissue plasminogen activator (rt-PA) fails to succeed in a subset of acute ischemic stroke (AIS) patients, while in approximately 6-8% of cases intracerebral hemorrhage (ICH) occurs as side effect.Here, we aimed to investigate α2-plasmin inhibitor (α2-PI) levels during thrombolysis and to find out whether they predict therapy outcomes in AIS patients.In this prospective, observational study, blood samples of 421 AIS patients, all undergoing i.v. thrombolysis by rt-PA within 4.5 h of their symptom onset, were taken before and 24 h after thrombolysis. In a subset of patients (n = 131), blood was also obtained immediately post-lysis. α2-PI activity and antigen levels were measured by chromogenic assay and an in-house ELISA detecting all forms of α2-PI. α2-PI Arg6Trp polymorphism was identified in all patients. Stroke severity was determined by NIHSS on admission and day 7. Therapy-associated ICH was classified according to ECASSII. Long-term outcomes were defined at 3 months post-event by the modified Rankin Scale (mRS).Median α2-PI activity and antigen levels showed a significant drop immediately post-lysis and increased to subnormal levels at 24 h post-event. Admission α2-PI levels showed a significant negative stepwise association with stroke severity. Patients with favorable long-term outcomes (mRS 0-1) had significantly higher admission α2-PI antigen levels (median:61.6 [IQR:55.9-70.5] mg/L) as compared to patients with poor outcomes (mRS 2-5: median:59.7 [IQR:54.5-69.1] and mRS 6: median:56.0 [IQR:48.5-61.0] mg/L, p < 0.001). In a Kaplan-Meier survival analysis, patients with an α2-PI antigen in the highest quartile on admission showed significantly better long-term survival as compared to those with α2-PI antigen in the lowest quartile (HR: 4.54; 95%CI:1.92-10.8, p < 0.001); however, in a multivariate analysis, a low admission α2-PI antigen did not prove to be an independent risk factor of poor long-term outcomes. In patients with therapy-related ICH (n = 34), admission α2-PI antigen levels were significantly, but only marginally, lower as compared to those without hemorrhage.Low α2-PI antigen levels on admission were associated with more severe strokes and poor long-term outcomes in this cohort. Our results suggest that in case of more severe strokes, α2-PI may be involved in the limited efficacy of rt-PA thrombolysis.}, keywords = {FIBRINOLYSIS; thrombolysis; outcome; Acute ischemic stroke; recombinant tissue plasminogen activator (rt-PA); intracerebral hemorrhage (ICH); α2-plasmin inhibitor}, year = {2022}, eissn = {2297-055X}, orcid-numbers = {Orbán-Kálmándi, Rita Angéla/0000-0002-2155-8279; Szegedi, István/0000-0003-4181-4361; Katona, Éva/0000-0003-3476-794X; Bagoly, Zsuzsa/0000-0001-5314-5607} } @article{MTMT:33060036, title = {EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.}, url = {https://m2.mtmt.hu/api/publication/33060036}, author = {Falanga, Anna and Leader, Avi and Ambaglio, Chiara and Bagoly, Zsuzsa and Castaman, Giancarlo and Elalamy, Ismail and Lecumberri, Ramon and Niessner, Alexander and Pabinger, Ingrid and Szmit, Sebastian and Trinchero, Alice and Ten Cate, Hugo and Rocca, Bianca}, doi = {10.1097/HS9.0000000000000750}, journal-iso = {HEMASPHERE}, journal = {HEMASPHERE}, volume = {6}, unique-id = {33060036}, abstract = {In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug-associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence-Based Medicine.}, year = {2022}, eissn = {2572-9241}, orcid-numbers = {Bagoly, Zsuzsa/0000-0001-5314-5607} } @article{MTMT:32797773, title = {Evidence for postnatal neurogenesis in the human amygdala}, url = {https://m2.mtmt.hu/api/publication/32797773}, author = {Roeder, Sebastian S. and Burkardt, Petra and Rost, Fabian and Rode, Julian and Brusch, Lutz and Coras, Roland and Englund, Elisabet and Håkansson, Karl and Possnert, Göran and Salehpour, Mehran and Primetzhofer, Daniel and Csiba, László and Molnár, Sarolta and Méhes, Gábor and Tonchev, Anton B. and Schwab, Stefan and Bergmann, Olaf and Huttner, Hagen B.}, doi = {10.1038/s42003-022-03299-8}, journal-iso = {COMMUN BIOL}, journal = {COMMUNICATIONS BIOLOGY}, volume = {5}, unique-id = {32797773}, abstract = {The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and C-14-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic C-14-concentrations in amygdala neurons compared with atmospheric C-14-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus. Lipofuscin labeling and (14) C retrospective birth-dating of neurons, along with mathematical modelling, here suggest continued postnatal neurogenesis in the human amygdala, rather than protracted maturation of developmentally generated neurons.}, year = {2022}, eissn = {2399-3642}, orcid-numbers = {Rost, Fabian/0000-0001-6466-2589; Rode, Julian/0000-0001-5185-2199; Salehpour, Mehran/0000-0003-2787-8801; Primetzhofer, Daniel/0000-0002-5815-3742; Bergmann, Olaf/0000-0003-1065-4107; Huttner, Hagen B./0000-0002-2586-9824} } @article{MTMT:32725654, title = {Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes - watch out for Piezo2}, url = {https://m2.mtmt.hu/api/publication/32725654}, author = {Sonkodi, Balázs and Hortobágyi, Tibor}, doi = {10.1515/med-2022-0444}, journal-iso = {OPEN MED-WARSAW}, journal = {OPEN MEDICINE}, volume = {17}, unique-id = {32725654}, issn = {2391-5463}, year = {2022}, eissn = {2391-5463}, pages = {397-402}, orcid-numbers = {Hortobágyi, Tibor/0000-0001-5732-7942} }