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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-merz Jorge Hernández-Campano Sergei A.Kirov Jesús m.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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Hypercalcemia: Is Dialysis Still an Option?

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Open Journal of Endocrine and metabolic Diseases 2022年第4期12卷 103-111页

作者： Basmat Amal Chouhani Yassine Allata Wafae Chouhani ghita Elberdai Nadia Kabbali Tarik Sqalli Houssaini Department of Nephrology Dialysis and Transplantation Hassan II University Hospital Fez Morocco Laboratory of Epidemiology and Health Science Research (ERESS) Faculty of Medicine-Fez University Sidi Mohammed Ben Abdelalh Fez Morocco

Hypercalcemia is a common disorder that can cause acute kidney failure, neurological damage up to coma, arrhythmia and cardiac arrest. The management of hypercalcemia is based on intravenous hydration with normal saline, when insufficient, bisphosphonate treatment is used. more recently, denosumab has shown significant benefit. Hemodialysis is an additional option in the treatment of severe refractory hypercalcemia when medical treatment is deemed ineffective or unavailable. It allows rapid correction of calcium levels, especially in patients with renal failure or cardiac co-morbidities, where hydration cannot be performed safely. The aim of our study was to compare hemodialysis as a therapeutic tool, to more conservative treatments. Our study is retrospective, descriptive, analytical and comparative, sprawling from January 2015 to June 2019 at the university hospital Hassan II in Fez. 78 patients with hypercalcemia were studied. The mean age was 55 ± 15 years and sex ratio m/F of 1.1. The mean corrected serum calcium at admission was 144 mg/l ± 23 mg/l. malignancies represented 72.7% of all etiologies. Kidney injury was observed in 50 of our patients (64%). mortality was noted in 16.6% of all cases. When comparing the 2 groups (patient on dialysis versus patient under other treatments), electrocardiogram abnormalities, patient who had high levels of calcium and those who had hyperparathyroidism were more likely to be on dialysis rate. In our study, even though we used relatively high calcium dialysate, we were able to achieve a decrease of 39% in patient’s calcemia in the hemodialysis group versus 27% decrease when using a combination of forced saline dieresis and bisphosphonate without a difference in term of mortality.

关键词： Hypercalcemia Dialysis Bisphosphonate mortality

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Lupus Nephritis Class II: A Challenging Entity

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Open Journal of Nephrology 2022年第2期12卷 203-213页

作者： Basmat Amal Chouhani ghita Elbardai Laila Tahiri Elousrouti Nadia Kabbali Hind Elfatemi Tarik Sqalli Houssaini Nephrology Dialysis and Transplantation Departement Hassan II University Hospital Fez Morocco Laboratory of Epidemiology and Health Science Research (ERESS) Faculty of Medicine-Fez Sidi Mohammed Ben Abdelalh University Fez Morocco Anatomopathology Department Hassan II University Hospital Fez Morocco Laboratory of Translational and Biomedical Research (RBT) Faculty of Medicine-Fez Sidi Mohammed Ben Abdellah University Fez Morocco

most of the literature focused on the proliferative forms of the lupic Glomerulonephritis. Clinicians are increasingly confronted with cases of lupic nephropathy purely mesangial (class II). The aim of our study is to describe the mode of presentation of the class II Lupus nephropathy, evaluate its evolutionary profile, and investigate possible risk factors for therapeutic misresponse, relapse or histological transformation. This is a retrospective descriptive and analytical study conducted in nephrology depratement at the Hassan II university hospital Fez from January 2009 until September 2018. We included 20 patients. The average age was 33.8 ± 7.25 years [22 - 50 years]. Nephropathy was inaugurated in half of the cases. The mean time of onset of nephropathy in relation to the lupic disease was 36.7 ± 45.4 months [1 - 144 months]. The main reason for consultation was non-nephrotic proteinuria (65%). Renal failure revealed diagnosis in three patients. All patients had a positive immunologic assessment. 90% of our patients received oral corticosteroid therapy with immunosuppressive therapy in 3 cases. Remission has been noted in all of our patients. After an average follow-up period of 39 ± 23 months [6 - 92 months], 45% relapsed. A second biopsy was performed in 80% of patients showing histologic transformation in four patients, requiring immunosuppressive therapy. The analytical study showed that the occurrence of relapse was significantly related to the presence of a known Lupus and its seniority. Proteinuria at 12 months was also significantly higher in the relapsed group. One patient died as a result of neurological complications. Another has Evolved into chronic end stage renal failure and has been put on hemodialysis.

关键词： Lupus Nephritis mesangial Nephropathy Relapse

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macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

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World Journal of methodology 2025年第1期15卷 88-94页

作者： Chinmay mahatme madhurima Kaushik Veerappan Rathinasabapathy Saravanan Karthik Kumar Virna m Shah Department of General Ophthalmology Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia Department of Neuro-ophthalmology Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia Department of Vitreoretina Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NmOSD)or myelin oligodendrocyte glycoprotein antibody disease(mOGAD),has a very similar presentation but different prognostic implications and longterm management *** and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated *** the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural *** To study the macular microvascular and structural changes on OCTA in atypical optic *** This observational cross-sectional study involved 8 NmOSD and 17 mOGAD patients,diagnosed serologically,as well as 10 healthy *** vascular density(mVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using *** There was a significant reduction in mVD in NmOSD and mOGAD affected as well as unaffected eyes when compared with healthy *** and mOGAD affected eyes had significant GCIPL thinning compared with healthy *** unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to mOGAD unaffected *** comparing NmOSD with mOGAD,there was no significant difference in terms of mVD or GCIPL in the affected or unaffected *** Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NmOSD and mOGAD cases.

关键词： Optical coherence tomography angiography Atypical optic neuritis macular microvascular changes Neuromyelitis optica spectrum disorders myelin oligodendrocyte glycoprotein antibody disorder

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Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal michele L Barbeau Charys m martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(mSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving mSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of mSK concepts(90.0%)and activity levels(97.7%).many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement mSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： medical education musculoskeletal Anatomy Exercise Online learning

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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： mackenzie m.Spicer Jianqi Yang Daniel Fu Alison N.DeVore marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in molecular medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

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Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam m.R.Groh moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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IPm Strategies and Their Dilemmas Including an Introduction to www. ***

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Journal of Integrative Agriculture 2014年第2期13卷 265-281页

作者： Lise Nistrup Jφrgensen mogens Stφvring Hovmφller Jens Grφnbk Hansen Poul Lassen Bill Clark Rosemary Bayles Bernd Rodemann Kerstin Flath margot Jahn Tomas Goral Jerzy Czembor J Philip Cheyron Claude maumene Claude De Pope Rita Ban ghita Cordsen Nielsen Gunilla Berg Depar tment of Agroecology Aarhus UniversityFlakkebjergFors?gsvej 1Slagelse 4200Denmark Aarhus University FoulumBlichers Allé 20Tjele 8830Denmark NIAB/TAG Huntingdon RoadCambridge CB3 0LEUnited Kingdom Julius Kuehn Institute Messerweg 11Braunsweig 38104Germany Julius Kuehn Institute Stahndorfer Damm 81Kleinmachnow14532Germany Plant Breeding and Acclimatization Institute IHAR-PIB RadzikowBlonie 05-870Poland Arvalis du Vegetal Boigneville 91720France Institut National de la Recherche Agronomique (INRA) Thiverval Grinon 78850France Szent István University Pater K.Street 1Godollo 2100Hungary Knowledge Centre for Agriculture SkejbyAarhus N 8200Denmark Swedish Board of Agriculture Plant Protection CentreAlnarp 23053Sweden

Information about disease management in winter wheat （Triticum aestiva） in eight European countries was collated and analysed by scientists and extension workers within the European Network for the Durable Exploitation of Crop Protection Strategies （ENDURE）. This included information about specific disease thresholds, decision support systems, host varieties, disease prevalence and pathogen virulence. major differences in disease prevalence and economic importance were observed. Septoria tritici blotch （mycosphaerella graminicola） was recognized as the most yield reducing disease in countries with intensive wheat production, but also rust diseases （Puccinia striiformis and Puccinia triticina）, powdery mildew （Blumeria graminis） and Fusarium head blight （Fusarium spp.） were seen as serious disease problems. Examples of current integrated pest management （IPm） strategies in different countries have been reported. Disease management and fungicide use patterns showed major differences, with an average input equivalent to 2.3 full dose rates （TFI） in the UK and a TFI of 0.6 in Denmark. These differences are most likely due to a combination of different cropping systems, climatic differences, disease prevalence, and socio-economic factors. The web based information platform *** was used for dissemination of information and results including information on control thresholds, cultural practices which can influence disease attack, fungicide efficacy, fungicide resistance, and pathogen virulence, which are all elements supporting 1Pm for disease control in wheat. The platform is open to all users. The target groups of EuroWheat information are researchers, advisors, breeders, and similar partners dealing with disease management in wheat.

关键词： winter wheat IPm fungicides diseases cultural methods

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What Is the Role of Endoscopic Retrograde Cholangio-Pancreato-Grahy in the management of Hepatic Hydatid Disease Complications?

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Open Journal of Gastroenterology 2020年第5期10卷 107-117页

作者： Hakima Abid ghita Ousseur Nada Lahmidani mounia El Yousfi Noureddin Aqodad mohammed El Abkari Adil Ibrahimi Dafr Allah Benajah Department of Hepato-Gastro-Enterology University Hospital Hassan II Fez Morocco Faculty of medicine Sidi Mohamed Ben Abdellah University Fez Morocco

Liver hydatid cyst is a parasitic disease that is endemic in morocco. Its gravity is essentially due to its complications, such as Intrabiliary rupture. The aim of our study was to evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy in the management of intrabiliary rupture of hydatid disease of the liver. materials and methods: This is a retrospective study in the department of Gastroenterology in the University Hospital Hassan II of Fez over a period of 12 years from march 2005 to October 2017. All patients admitted for hepatic hydatid disease and who received ERCP were included. We analyzed the success rate of catheterization of the common bile duct (CBD), the successful clearance of the bile duct and the complications. Results: 2860 patients had received therapeutic ERCP, 151 patients (5.3%) had hepatic hydatid disease, 112 of which had intrabiliary disruption of hepatic hydatid and 39 patients were admitted for sphincteromy for reversal of the flow after surgery of hydatid cyst. The average age of our patients was 41 years old [12 - 85]. The sex ratio F/H = was 1.12. 74% (N = 112) patients were admitted to a table cholangitis and 26% of cases were operated for KHF fistulized in the bile ducts with persistence of a large biliary flow in post-operative (39 cases). The success of initial catheterization of the commun bile duct was achieved for 138 patients (91%) or obtained secondarily after precut for 13 patients. The evacuation of hydatid membranes was carried out in 51% of them (N = 78);twenty two (14.5%) patients had one or more calculations with or without hydatid membranes. A case of gastrointestinal bleeding post ERCP was observed. All the patients followed evolved well in the long term except for two patients who presented in few months after the first ERCP severe cholangitis which required the use of a second ERCP with successful evacuation of membranes. Conclusion: In our study, endoscopic management o

关键词： Hydatid Cyst Intrabiliary Rupture Complications Endoscopic Retrograde Cholangiopancreatography Endoscopic Sphincterotomy

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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