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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of Biology University of Patras Laboratory of Cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

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Determinants of inspiratory muscle function in healthy children

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Journal of Sport and Health Science 2019年第2期8卷 183-188页

作者： Theodore Dassios Gabriel dimitriou Department of Child Health King's College Hospital Department of Paediatrics University of Patras Medical School

Background: Children are affected by disorders that have an impact on the respiratory muscles. Inspiratory muscle function can be assessed by means of the noninvasive tension–time index of the inspiratory muscles(TTImus). Our objectives were to identify the determinants of TTImus in healthy children and to report normal values of TTImus in this population.Methods: We measured weight, height, upper arm muscle area(UAMA), and TTImusin 96 children aged 6–18 years. The level and frequency of aerobic activity was assessed by questionnaire.Results: TTImuswas significantly lower in male subjects(0.095 ± 0.038, mean ± SD) compared with female subjects(0.126 ± 0.056)(p = 0.002).TTImus was significantly lower in regularly exercising(0.093 ± 0.040) compared with nonexercising subjects(0.130 ± 0.053)(p variate logistic regression analysis revealed that height and aerobic exercise were significantly related to TTImus independently of age, weight, and UAMA. The predictive regression equation for TTImus in male subjects was TTImus = 0.228-0.001 × height(cm), and in female subjects it was TTImus = 0.320-0.001 × height(cm).Conclusion: Gender, age, anthropometry, skeletal muscularity, and aerobic exercise are significantly associated with indices of inspiratory muscle function in children. Normal values of TTImus in healthy children are reported.

关键词： Aerobic exercise Children Inspiratory muscle function Maximal inspiratory pressure Skeletal muscle function Tension-time index of the inspiratory muscles

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The Table Auto-Regressive Moving-Average Model for (Categorical) Stationary Series: Mathematical Perspectives (Invertibility;Maximum Likelihood Estimation)

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Open Journal of Statistics 2022年第3期12卷 385-407页

作者： Chrysoula dimitriou-Fakalou Independent Researcher Athens Greece

Once invertibility for a causal TARMA series is defined and accompanied by conditions on the probability parameters of the model, all focus concentrates on the maximum likelihood estimators. Under the coexistence of essential causality and invertibility, the estimators are shown to be convergent to the real values and asymptotically obedient to the Gaussian distribution: their variance matrix identifies with a classic result. Some real-like examples are simulated and simplification attempts include the derivation of the non-parametric chi-square test extension for stationary TAR series.

关键词： Asymptotic Normality Consistency Scores Efficiency Strict Stationarity

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Modular Filter Convergence Theorems for Urysohn Integral Operators and Applications

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Acta Mathematica Sinica,English Series 2013年第6期29卷 1055-1066页

作者： Antonio BOCCUTO Xenofon dimitriou Dipartimento di Matematica e Informatica via Vanvitelli Department of Mathematics University of Athens Panepistimiopolis

We prove some versions of modular convergence theorems for nonlinear Urysohn-type integral operators with respect to filter convergence. We consider pointwise filter convergence of functions giving also some applicati... 详细信息

关键词： Egorov filter Lebesgue filter filter convergence filter exhaustiveness filter singularity integral operator Mellin operator modular convergence modular space

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Biomechanical Analysis of Personalised 3D-Printed Clavicle Plates of Different Materials to Treat Midshaft Clavicle Fractures

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Journal of Shanghai Jiaotong university(Science) 2021年第3期26卷 259-266页

作者：程荣山蒋子昂 dimitriou dimitriou 龚伟华蔡宗远 School of Biomedical Engineering&Med-X Research Institute Shanghai Jiao Tong UniversityShanghai200030China Department of Orthopaedic Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200011China Department of Orthopedics Bürgerspital SolothurnSchöngrünstrasse 42CH-4500SolothurnSwitzerland

This study was aimed at comparing the biomechanical performance of personalised 3D-printed clavicle plates of different materials to treat midshaft clavicle fractures with the finite element(FE)method.The FE model of a fractured clavicle with a personalised 3D-printed clavicle plate and screws was constructed.Three types of materials were simulated,including stainless steel,titanium alloy,and magnesium alloy.Two loading conditions(axial compression and inferior bending)were applied at the distal end of the clavicle to simulate arm abduction.Plate stiffness,peak stress,and bone strain at the clavicle fracture site were measured and compared.The stiffness of the stainless steel clavicle plate was significantly greater than that of the titanium alloy clavicle plate.The stiffness of the magnesium alloy clavicle plate was similar to that of the intact clavicle;peak stress of the magnesium alloy clavicle plate was the lowest;thus,it had less stress-shielding effects on bone formation.The magnesium alloy clavicle plate was more likely to form bone by distributing proper strain at the clavicle fracture site.According to the influence of different materials on the tensile strength,magnesium alloy clavicle plates might be preferred owing to their bionic stiffness in the treatment of patients with a low risk of falling.For patients who engage in contact sports,a titanium alloy clavicle plate might be more suitable.

关键词： personalised treatment 3D printing clavicle plate biomechanical analysis

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Low rectal cancer:Sphincter preserving techniques-selection of patients,techniques and outcomes

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World Journal of Gastrointestinal Oncology 2015年第7期7卷 55-70页

作者： Nikoletta dimitriou Othon Michail Dimitrios Moris John Griniatsos 1st Department of Surgery University of AthensMedical SchoolLaiko Hospital

Low rectal cancer is traditionally treated by abdominoperineal resection. In recent years, several new techniques for the treatment of very low rectal cancer patients aiming to preserve the gastrointestinal continuity and to improve both the oncological as well as the functional outcomes, have been emerged. Literature suggest that when the intersphincteric resection is applied in T1-3 tumors located within 30-35 mm from the anal verge, is technically feasible, safe, with equal oncological outcomes compared to conventional surgery and acceptable quality of life. The Anterior Perineal Plan E for Ultra-low Anterior Resection technique, is not disrupting the sphincters, but carries a high complication rate, while the reports on the oncological and functional outcomes are limited. Transanal Endoscopic Micro Surgery(TEM) and Trans Anal Minimally Invasive Surgery(TAMIS) should represent the treatment of choice for T1 rectal tumors, with specific criteria according to the NCCN guidelines and favorable pathologic features. Alternatively to the standard conventional surgery, neoadjuvant chemo-radiotherapy followed by TEM or TAMIS seems promising for tumors of a local stage T1sm2-3 or T2. Transanal Total Mesorectal Excision should be performed only when a board approved protocol is available by colorectal surgeons with extensive experience in minimally invasive and transanal endoscopic surgery.

关键词： Low rectal cancer Sphincter preservingsurgery Intersphincteric resection Anterior PerinealPlanE for Ultra-low Anterior Resection of the Rectum Total mesorectal excision TransAnal Minimally InvasiveSurgery Transanal Total Mesorectal Excision Quality oflife Oncological outcome Functional outcome

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Lymph node,peritoneal and bone marrow micrometastases in gastric cancer:Their clinical significance

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World Journal of Gastrointestinal Oncology 2012年第2期4卷 16-21页

作者： John Griniatsos Othon Michail Nikoletta dimitriou Ioannis Karavokyros 1st Department of Surgery University of AthensMedical SchoolGR 115-27AthensGreece

The 7th TNM classification clearly states that micro-metastases detected by morphological techniques(HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease(pN1mi or M1),while patients in whom micrometas-tases are detected by non-morphological techniques(e.g.,ow cytometry,reverse-transcriptase polymerase chain reaction) should still be classif ied as N0 or M0.In gastric cancer patients,micrometastases have been de-tected in lymph nodes,the peritoneal cavity and bone marrow.However,the clinical implications and/or their prognostic signif icance are still a matter of debate.Cur-rent literature suggests that lymph node micrometasta-ses should be encountered for the loco-regional staging of the disease,while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes.Peritoneal fluid cytology ex-amination should be obligatorily performed in pT3 or pT4 tumors.A positive cytology classif ies gastric cancer patients as stage Ⅳ.Although a curative resection is not precluded,these patients face an overall dismal prognosis.Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further.Gas-tric cancer cells are detected with high incidence in the bone marrow.However,the published results make comparison of data between groups almost impossible due to severe methodological problems.If these meth-odological problems are overcome in the future,specif ic target therapies may be designed for specif ic groups of patients.

关键词： Gastric cancer D2 lymphadenectomy Lymph node micrometastases Peritoneal micrometastases Bone marrow micrometastases

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Chylorrhea complicating D2＋a gastrectomy： review of the literature and clarification of terminology apropos one case

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Chinese Medical Journal 2010年第16期123卷 2279-2283页

作者： John Griniatsos Nikoletta dimitriou Despina Kyriaki Antigoni Velidaki Stavros Sougioultzis Paris Pappas Department of Surgery University of AthenaMedical School LAIKO Hospital Athens Greece Department of Nuclear Medicine University of AthenaMedical School LAIKO Hospital Athens Greece Gastroenterology Unit Department of Pathologic Physiology University of AthenaMedical School LAIKO Hospital Athens Greece Department of Radiology University of AthenaMedical School LAIKO Hospital Athens Greece

Lymphatic complications leading to retention,accumulation or drainage of peritoneal fluid are frequently encountered following extended or superextended lymphadenectomy for gastric cancer.1 The vast majority of these drainages usually subsides spontaneously, but in some instances they can persist for long period of time causing significant morbidity.However, the classification,

关键词： chylous leakage D2 gastrectomy extended lymphadenectomy gastric cancer lymphoscintigraphy

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Retroperitoneal perivascular epithelioid cell tumours: A case report and review of literature

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World Journal of Clinical Cases 2019年第21期7卷 3524-3534页

作者： Zisis Touloumis Niki Giannakou Christos Sioros Argiro Trigka Maria Cheilakea Nikoletta dimitriou John Griniatsos Department of Surgery Athens Medical GroupAthens 11525Greece Department of Pathology Athens Medical GroupAthens 11525Greece Emergency Department Konstantopouleio General HospitalN.Ionia 14233Greece Department of Surgery National and Kapodistrian University of AthensAthens 11527Greece

BACKGROUND The perivascular epithelioid cell tumour(PEComa)family of tumours mainly includes renal and hepatic angiomyolipomas,pulmonary lymphangioleiomyomatosis and clear cell“sugar”tumour of the lung.Several uncommon tumours with similar morphological and immunophenotypical characteristics arising at a variety of sites(abdominal cavity,digestive tract,retroperitoneum,skin,soft tissue and bones)are also included in the PEComa family and are referred to as PEComas not otherwise specified.CASE SUMMARY We present a 37-year-old female patient who underwent resection of an 8.5 cm×8 cm×4 cm retroperitoneal tumour,which eventually was diagnosed as PEComa of uncertain biological behaviour.Three years after the operation,the patient remains without any evidence of recurrence.A search was performed in the Medline and EMBASE databases for articles published between 1996 and 2018,and we identified 31 articles related to retroperitoneal and perinephric PEComas.We focused on sex,age,maximum dimension,histological and immunohistochemical characteristics of the tumour,follow-up and long-term outcome.Thirty-four retroperitoneal(including the present one)and ten perinephric PEComas were identified,carrying a malignant potential rate of 44%and 60%,respectively.Nearly half of the potentially malignant PEComas presented with or developed metastases during the course of the disease.CONCLUSION Retroperitoneal PEComas are not as indolent as they are supposed to be.Radical surgical resection constitutes the treatment of choice for localized disease,while mammalian target of the rapamycin(mTOR)inhibitors constitute the most promising therapy for disseminated disease.The role of mTOR inhibitors as adjuvant or neoadjuvant therapies needs to be evaluated in the future.

关键词： Perivascular epithelioid cell tumour Retroperitoneum Mammalian target of the rapamycin inhibitors Tuberous sclerosis complex Case report Treatment

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Testing optically stimulated luminescence dating on sand-sized quartz of deltaic deposits from the Sperchios delta plain, central Greece

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Journal of Palaeogeography 2018年第2期7卷 130-145页

作者： Evangelos Tsakalos Elias dimitriou Maria Kazantzaki Christos Anagnostou John Christodoulakis Eleni Filippaki Hellenic Centre for Marine Research Institute of Inland Waters Laboratory of Archaeometry Institute of Nanoscience and Nanotechnology National Centre for Scientific Research N.C.S.R. "Demokritos" Department of Geophysics Division of Earth and Planetary Sciences Graduate School of Science Kyoto University Hellenic Centre of Marine Research Institute of Oceanography Climate Research Group Division of Environmental Physics and Meteorology Faculty of Physics National and Kapodistrian University of Athens

This study reports on the first investigation into the potential of luminescence dating to establish a chronological framework for the depositional sequences of the Sperchios delta plain, central Greece. A series of three borehole cores(20 m deep) and two shallow cores(4 m deep), from across the delta plain, were extracted, and samples were collected for luminescence dating. The luminescence ages of sand-sized quartz grains were obtained from small aliquots of quartz, using the Single-Aliquot Regenerative-dose(SAR) protocol.The equivalent dose determination included a series of tests and the selection of the Minimum Age Model(MAM) as the most appropriate statistical model. This made it possible to confirm the applicability of quartz Optically Stimulated Luminescence(OSL) dating to establish absolute chronology for deltaic sediments from the Sperchios delta plain.Testing age results of the five cores showed that the deltaic sediments were deposited during the Holocene.A relatively rapid deposition is implied for the top14 m possibly as a result of the deceleration in the rate of the sea-level rise and the transition to terrestrial conditions, while on the deeper parts, the reduced sedimentation rate may indicate a lagoonal or coastal environment.

关键词： Luminescence dating Holocene Sedimentation rates Deltaic deposits Sperchios delta plain Central Greece

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