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Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system

Translational Neurodegeneration 2022年第1期11卷 667-689页

作者： Douglas M.Lopes sophie K.Llewellyn Ian F.Harrison Division of Medicine Department of ImagingCentre for Advanced Biomedical ImagingFaculty of Medical SciencesUniversity College LondonPaul O’Gorman Building72 Huntley StreetLondon WC1E 6DDUK

Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are characterised by the accumulation of misfolded protein deposits in the brain, leading to a progressive destabilisation of the neuronal network and neuronal death. Among the proteins that can abnormally accumulate are tau and α-synuclein, which can propagate in a prion-like manner and which upon aggregation, represent the most common intracellular proteinaceous lesions associated with neurodegeneration. For years it was thought that these intracellular proteins and their accumulation had no immediate relationship with extracellular homeostasis pathways such as the glymphatic clearance system;however, mounting evidence has now suggested that this is not the case. The involvement of the glymphatic system in neurodegenerative disease is yet to be fully defined;however, it is becoming increasingly clear that this pathway contributes to parenchymal solute clearance. Importantly, recent data show that proteins prone to intracellular accumulation are subject to glymphatic clearance, suggesting that this system plays a key role in many neurological disorders. In this review, we provide a background on the biology of tau and α-synuclein and discuss the latest findings on the cell-to-cell propagation mechanisms of these proteins. Importantly, we discuss recent data demonstrating that manipulation of the glymphatic system may have the potential to alleviate and reduce pathogenic accumulation of propagation-prone intracellular cytotoxic proteins. Furthermore, we will allude to the latest potential therapeutic opportunities targeting the glymphatic system that might have an impact as disease modifiers in neurodegenerative diseases.

关键词： Glymphatic Propagation Tauopathy Synucleinopathy Clearance Aquaporin-4

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Military Threats to Terrestrial Resources Not Restricted to Wartime： A Case Study from Guam

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Journal of environmental Science and engineering 2011年第9期5卷 1198-1214页

作者： T.e. Marler A. moore Western Pacific Tropical Research Center University of Guam UOG Station Mangilao Guam 96923 USA

The onset of construction and personnel transfers to the islands of Guam and Tinian present a case study in which peacetime military operations threaten conservation of environmental resources. The planning process indicates land conversion, increased population, and invasive species arriving in the midst of increased imports are among the major impending threats, especially to terrestrial biological resources. We discuss historical events that have marginalized the contributions of local stakeholders, mistake-ridden planning processes revealing inadequate efforts to safeguard the environment, and compelling evidence that predicts a trajectory targeting imminent damage of terrestrial resources. We contend these developments present a case study within the ecological ethics discipline whereby peacetime military operations push conservation of the environment to the sidelines in the name of national defense. We conclude that conservation of environmental resources is not ancillary to national security, it is integral. Wartime military damage to natural resources is unavoidable, therefore, peacetime military operations should embrace conservation priorities to a greater degree.

关键词： Colonialism invasive species land conversion urbanization

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Utility of a hemoglobin A1C obtained at the first prenatal visit

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World Journal of Obstetrics and Gynecology 2014年第3期3卷 130-133页

作者： Lisa e moore Diana Clokey Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine University of New Mexico

AIM： To evaluate the utility of the hemoglobin A1C （HbA1C） at the frst prenatal visit as a triaging tool in patients at high risk for gestational diabetes （GDM）.MeTHODS： The HbA1C was obtained at the frst prenatal visit prior to 20 wk. Women with a HbA1C ≥ 6.5% （group one） were instructed on diet and daily self-monitoring of blood glucose. Women with a HbA1C between 5.7%-6.4% （group two） were offered testing or daily self-monitoring of blood glucose. Women with a HbA1C 〈 5.7% （group three） were tested at 24-28 wk. Patients were tested for GDM using the two step testing and Carpenter and Coustan values as cutoffs. Medication was started if patients failed to meet glycemic goals of fasting ≤ 95 mg/dL （5.3 mmol/L） and 2 h postprandial ≤ 120 mg/dL （6.7 mmol/L）.ReSULTS： In group one （n = 16）, 15/16 （95%） re-quired medication to achieve euglycemia. The mean gestational age at which medication was required was early at 14 ± 6 wk. Postpartum, 14/16 patients （87%） remained diabetic. Group two contained 82 patients. Sixty-sixpatients （80%） were given a diagnosis of GDM and 52 patients （64%） required medication. The mean gestational age at which medication was started in group two was 20 ± 7.8 wk. There were 205 patients in group three, 18 patients （8.7%） were diagnosed with GDM and 13 patients （6%） required medication. In comparison to group three, patients in group one were 220 times more likely to require medication （95%CI： 26.9- 〉 999, P 〈 0.0001）. Patients in group two were 26 times more likely to require medication （95%CI： 12.5-54.3, P 〈 0.0001）.

关键词： Gestational diabetes Pregnancy Hemoglo-bin A1C Glycosylated hemoglobin

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Clinical forensic imaging and fundamental rights in Austria

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Forensic Sciences Research 2017年第2期2卷 65-74页

作者： sophie Kerbacher Michael Pfeifer Bridgette Webb Reingard Riener-Hofer Ludwig Boltzmann Institute for Clinical Forensic Imaging Ludwig Boltzmann GesellschaftGrazAustria

Clinical forensic imaging encompasses the diverse application of imaging procedures that serve the same purpose:to enable the analysis and investigation of criminal activities and consequences of a *** kinds of imaging techniques and their corresponding images can be subsumed under“forensigraphy”,a more comprehensive term for forensic imaging created by the Ludwig Boltzmann Institute for Clinical Forensic Imaging in Graz,*** the word forensigraphy suggests,criminal imaging material should be of use in forensic ***,this can lead to new findings that would not have been revealed without the application of imaging techniques and are moreover admissible as evidence in criminal ***,the admissibility of evidence can only be facilitated through the implementation of clinical forensic imaging techniques into the forensic routine case work,which requires a precise pre-analysis of the corresponding legal *** taking and displaying internal images of a person’s body touches upon various aspects of one’s physical and psychological integrity,imaging methods in general and clinical forensic imaging methods especially have a strong impact on and interfere regularly with the fundamental rights of the concerned *** with regard to a possible medical context,certain legal regulations have to be taken into ***,this paper examines forensic imaging in the field of radiological forensigraphy,specifically its in vivo(***)*** is designed to enlighten readers as to the great significance of legal barriers that emerge from fundamental rights,as laid down in the european Convention on Human Rights(eCHR),when dealing with clinical forensic *** a result,the legal framework of clinical forensic imaging procedures are comprehensively described,the relevant fundamental rights,especially the right to respect for private and family life,the right to data protection and certain procedu

关键词： Forensic science clinical forensic medicine clinical forensic imaging forensigraphy fundamental rights physical examination criminal proceedings eCHR

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Introduction to the practice of statistics 4th ed.

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2003年

作者： moore, David S

来源：畅想之星图书光盘版（南... 评论

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Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series

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World Journal of Clinical Cases 2016年第7期4卷 172-176页

作者： Pamela D moore Ashraf S Gorgey Rodney C Wade Refka e Khalil Timothy D Lavis Rehan Khan Robert A Adler Spinal Cord Injury Service and Disorders Hunter Holmes Mc Guire VA Medical Center Physical Medicine and Rehabilitation Virginia Commonwealth University Radiology Service Hunter Holmes McG uire VA Medical Center endocrinology Service Hunter Holmes Mc Guire VA Medical Center endocrine Division Virginia Commonwealth University School of Medicine

Neuromuscular electrical stimulation(NMeS) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). However both interventions might increase heterotopic ossification(HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMeS resistance training(RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches(4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMeS-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas(CSA) of thewhole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A(NMeS-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B(TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMeS-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of preexisting HO.

关键词： Heterotopic ossification Neuromuscular electrical stimulation Testosterone Resistance training Spinal cord injury

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Plastome characteristics of Cannabaceae

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Plant Diversity 2018年第3期40卷 127-137页

作者： Huanlei Zhang Jianjun Jin Michael J.moore Tingshuang Yi Dezhu Li Germplasm Bank of Wild Species Kunming Institute of Botany Chinese Academy of Sciences Kunming College of Life Sciences University of Chinese Academy of Sciences Department of Biology Oberlin College

Cannabaceae is an economically important family that includes ten genera and ca. 117 accepted *** explore the structure and size variation of their plastomes, we sequenced ten plastomes representing all ten genera of Cannabaceae. each plastome possessed the typical angiosperm quadripartite structure and contained a total of 128 genes. The Inverted Repeat(IR) regions in five plastomes had experienced small expansions(330 e983 bp) into the Large Single-Copy(LSC) region. The plastome of Chaetachme aristata has experienced a 942-bp IR contraction and lost rpl22 and rps19 in its IRs. The substitution rates of rps19 and rpl22 decreased after they shifted from the LSC to IR. A 270-bp inversion was detected in the Parasponia rugosa plastome, which might have been mediated by 18-bp inverted repeats. Repeat sequences, simple sequence repeats, and nucleotide substitution rates varied among these *** markers with more than 13% variable sites and 5% parsimony-informative sites were identified, which may be useful for further phylogenetic analysis and species identification. Our results show strong support for a sister relationship between Gironniera and Lozanell(BS ? 100). Celtis, CannabisHumulus, Chaetachme-Pteroceltis, and Trema-Parasponia formed a strongly supported clade, and their relationships were well resolved with strong support(BS ? 100). The availability of these ten plastomes provides valuable genetic information for accurately identifying species, clarifying taxonomy and reconstructing the intergeneric phylogeny of Cannabaceae.

关键词： Plastome IR expansion/contraction Repeats SSR Sequence divergence Phylogenomics

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Affect regulation in psychoanalytic treatments of patients with a borderline personality disorder–psychoanalysis and psychodynamic psychotherapy–a comparison

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World Journal of Psychiatry 2021年第12期11卷 1328-1345页

作者： Dagmar Steinmair Guoruey Wong sophie Frantal Christine Rohm Henriette Löffler-Stastka Department of Psychoanalysis and Psychotherapy Medical University of ViennaWien 1090Austria Karl Landsteiner University of Health Sciences Dr.Karl-Dorrek-Straße 30Krems 3500Austria Department of Ophtalmology University Hospital St.PöltenSt.Pölten 3100Austria Facultéde Médecine Universitéde MontréalMontréal H3C 3J7QuébecCanada

BACKGROUND A recent meta-analysis has confirmed that the effects of psychotherapy on patients with borderline personality disorders(BPD)are still insufficiently *** of differences between different types of therapies has been *** To study repetitive interaction patterns in patients with BPD undergoing either psychoanalysis or psychodynamic *** Psychoanalysis(PSA)or psychodynamic psychotherapy(PDT)was administered to 10 patients each,the two groups were *** regimens were applied according to care as usual/manualized including quality control and supervision as *** to one of the groups was done after baseline *** classical PSA(n=10)and PDT(n=10),semiannually,recordings(audio or video)of five consecutive therapy sessions were taken over three years for an ex-post *** patients'characteristics,such as affect parameters[Affect regulation and experience Q-sort(AReQ)],quality of object relations(quality of object relations scale)and personality traits[Shedler-Westen Assessment Procedure(SWAP-200)]were analyzed retrospectively by independent *** action(psychotherapy process Q-sort)and affective(re)actions of the patients(AReQ)were then analyzed in relation to changes found in the patients'*** During the first year of therapy(PSA:n=10;PDT:n=9),the therapeutic method PSA was associated with significant improvements in the variable"SWAP Borderline",while in PDT change was not significantly different to baseline(PSA:P=0.04;PDT:P=0.33).Long-term results and follow up was available for seven participants in PSA and for five in PDT after three years;change in SWAP borderline for the whole sample was not significant at this time point when confronting to baseline(P=0.545).However,differences between PSA and PDT were significant when analyzing the“mean change”in the SWAP Borderline variable after one year of therapy(P=0.024):PSA led to slightly increased BPD sy

关键词： Psychoanalysis Psychodynamic psychotherapy Borderline personality disorder Affect regulation Affect regulation and experience Q-sort Transference

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Diurnal changes in postural control in normal children: Computerized static and dynamic assessments

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Burns & Trauma 2014年第3期2卷 130-135页

作者： sophie Bourelle Redha Taiar Benoit Berge Vincent Gautheron Jerome Cottalorda Department of Pediatric Surgery University Hospital of Reims Department of Sport Sciences University of Reims Champaign euraxi Pharma Joué-Lès-Tours Physical and Rehabilitation Medicine Service University Hospital Saint-Etienne Department of Orthopaedic Pediatric and Plastic Surgery University Hospital MontpellierFrance

Mild traumatic brain injury (mTBI) causes postural control deficits and accordingly comparison of aberrant postural control against normal postural control may help diagnose mTBI. However, in the current literature, little is known regarding the normal pattern of postural control in young children. This study was therefore conducted as an effort to fill this knowledge gap. eight normal school-aged children participated. Posture assessment was conducted before (7-8 a.m. in the morning) and after (4-7 p.m. in the after-noon) school on regular school days using the Balance Master? evaluation system composed of 3 static tests and 2 dynamic balance tests. A significant difference in the weight-bearing squats was detected between morning hours and afternoon hours (P end of afternoon, the body weight was borne mainly on the left side with the knee fully extended and at various degrees of knee flexion. A significantly better directional control of the lateral rhythmic weight shifts was observed at the end of the afternoon than at morning hours (P e inconsistent with results from previous studies in adults, sug-gesting age-related differences in posture control in humans. On a regular school day, the capacity of postural control and laterality or medio-lateral balance in children varies between morning and afternoon hours. We suggest that posturographic assessment in children, either in normal (e.g., physical education and sports training) or in abnormal conditions (e.g., mTBI-associated balance disorders), be better performed late in the afternoon.

关键词： Child postural control posturography diurnal patterns trauma prevention

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In vitro and in vivo proves of concept for the use of a chemically cross-linked poly(ester-urethaneurea)scaffold as an easy handling elastomeric biomaterial for bone regeneration

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Regenerative Biomaterials 2019年第6期6卷 311-323页

作者： Geraldine Rohman Sylvie Changotade sophie Frasca Salah Ramtani Anne Consalus Credson Langueh Jean-Marc Collombet Didier Lutomski Universite Paris 13 Sorbonne Paris CiteTissue Engineering and Proteomics(TIP)TeamCSPBATUMR CNRS 724474 rue Marcel Cachin93000 BobignyFrance Departement Soutien Medico-Chirurgical des Forces(SMCF) BP73Institut de Recherche Biomedicale des Armees(IRBA)91223 Bretigny-sur-Orge CedexFrance UniversiteParis 13 Sorbonne Paris CiteLBPS TeamCSPBATUMR CNRS 724499 Avenue Jean-Baptiste Clement93430 VilletaneuseFrance

Bone loss can occur as a result of various pathologies,traumas and injuries and poor bone healing leads to functionally debilitating condition,loss of self-sufficiency and deterioration in life *** the increasing incidence of facial trauma and the emergence of new procedural techniques,advanced scaffolds are currently developed as substitutes for bone tissue *** this study,we investigated the capability of a chemically cross-linked e-caprolactone-based poly(esterurethane-urea)(PCLU)scaffold to support bone *** vitro assays demonstrated that PCLU scaffolds could be colonized by cells through direct cell seeding and cell migration from outside to scaffold ***,PCLU scaffolds could provide a suitable environment for stem cells proliferation in a 3D spatial arrangement,and allowed osteogenic differentiation under appropriate *** vivo results revealed the osteogenic properties of PCLU scaffolds through a drilled-hole femoral bone defect repair improvement in *** histology and microtomography analysis,we showed that PCLU scaffolds fit well the bone cavity and were eventually entrapped between the newly formed ***,no sign of inflammation or rejection was *** envision that PCLU scaffolds can provide the clinicians with a substitute having appropriate characteristics for the treatment of bone defects.

关键词： bone regeneration scaffold elastomer PeUU PCLU

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