National Taiwan University Repository

    Intravenous Immunoglobulin (Ivig) Protects the Brain against Experimental Stroke by Preventing Complement-Mediated Neuronal Cell Death

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    Stroke is among the three leading causes of death worldwide and the most frequent cause of permanent disability. Brain ischemia induces an inflammatory response involving activated complement fragments. Here we show that i.v. Ig ( IVIG) treatment, which scavenges complement fragments, protects brain cells against the deleterious effects of experimental ischemia and reperfusion (I/R) and prevents I/R -induced mortality in mice . Animals administered IVIG either 30 min before ischemia or after 3 h of reperfusion exhibited a 50-60% reduction of brain infarct size and a 2- to 3-fold improvement of the functional outcome. Even a single low dose of IVIG given after stroke was effective. IVIG was protective in the nonreperfusion model of murine stroke as well and did not exert any peripheral effects. Human IgG as well as intrinsic murine C3 levels were significantly higher in the infarcted brain region compared with the noninjured side, and their physical association was demonstrated by immuno -coprecipitation. C5-deficient mice were significantly protected from I/R injury compared with their wild-type littermates. Exposure of cultured neurons to oxygen/glucose deprivation resulted in increased levels of C3 associated with activation of caspase 3, a marker of apoptosis; both signals were attenuated with IVIG treatment. Our data suggest a major role for complement-mediated cell death in ischemic brain injury and the prospect of using IVIG in relatively low doses as an interventional therapy for stroke

    Recent Developments in Neurofibromatosis Type 1

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    Purpose of review This review summarizes the recent clinical and genetic developments in neurofibromatosis type 1 (NF1) and provides an insight into the possible underlying pathomechanisms. Recent findings NF1, or von Recklinghausen disease, is one of the most common hereditary neurocutaneous disorders in humans. Clinically, NF1 is characterized by cafe-au-lait spots, freckling, skin neurofibroma, plexiform neurofibroma, bony defects, Lisch nodules and tumors of the central nervous system. The responsible gene, NF1, encodes a 2818 amino acid protein (neurofibromin). Pathological mutations range from single nucleotide substitutions to large -scale genomic deletions dispersed throughout the gene. In addition to the conventional mutation screening methods, a DNA chip microarray-based technology, combinational sequence-based hybridization, has been introduced to expedite mutation detection. Functional analysis has become more amenable following the development of the following: (1 ) primary Schwann cell cultures from NF1 patients; (2) mouse models; (3) proteomic technologies; and (4) mRNA silencing by RNA interference. These studies have shown that neurofibromin plays a role in adenylate cyclase and AKT- mTOR mediated pathways. It also appears to affect Ras-GTPase activating protein activity through the phosphorylation of protein kinase C which impacts on cell motility by binding with actin in the cytoskeleton. Summary Recent advances in the clinical features and molecular genetics of NF1 will be discussed together with insights into the underlying pathomechanisms of NF1

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    A Study on the Flexibility of Body Ownership

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    近年來對於橡膠手錯覺(Rubber Hand Illusion)的研究指出,身體歸屬感(The sense of body ownership)有許多限制的因素,但它仍舊可以有相當大的展延性。為了要了解這些限制的極限,確切地思考此身體歸屬感到底能有多大的展延性,就顯得非常重要了。除此之外,哲學現象學上將與身體相關的自我意識區分成“做為主體之身體”(body-as-subject)及“做為對象之身體”(body-as-object)兩種不能同時發生的身體經驗,此二分法也形成身體歸屬感理論上的限制。在本研究中,針對此議題我用以下問題來探討:(1)正常的人是否有可能經歷擁有四隻手的錯覺經驗?(2)人是否可以同時擁有“做為主體之身體”及“做為對象之身體”的經驗?當受試者帶上頭戴式立體顯示器(HMD)時,會將實驗者的第一人稱觀點(1PP)當成自己的第一人稱觀點(adopted 1PP)。受試者與實驗者面對面而坐,在兩隻手條件下,受試者從adopted 1PP的觀點看到實驗者的兩隻手。在四隻手條件下,受試者除了從adopted 1PP看到的兩隻手之外,同時從第三人稱觀點(adopted 3PP)看到自己的兩隻手在自己對面。受試者感受到自己的真手與看到的手正在同步或不同步地被刷。 我發現:(1)在“被動的兩隻手”實驗中,同步的刷手會引發新式樣的橡膠手錯覺。(2)在“被動的四隻手”實驗中,受試者主觀感受到的觸覺位置與手的歸屬感是可以分離的。(3)在“主動的四隻手”實驗中,受試者被要求要彈動雙手食指,而實驗者模仿受試者的動作。當四隻手同步地做相同的動作時,令人驚訝地發現,有高達68%的受試者同意或非常同意:“我曾覺得好像多了兩隻手”。膚電反應(SCR)客觀的量測也支持此一結果。此實驗呈現出身體歸屬感的展延性,遠超乎以前研究者所建議的程度。 我用本研究成果來探究Tsakiris(2010)對身體歸屬感所提出的“認知神經模型”(neurocognitive model of body ownership)理論,並論述該理論未涵蓋動作感及視覺觀點的不足。哲學上對身體歸屬感理論上二分法的限制,本研究提出了一個有力的反證。本研究結果指出,受試者對1PP-hands做動作的手既作為經驗的主體,也同時將它作為經驗的客體。 本行為研究的實驗成果,率先證實正常人可以產生擁有四隻手的主觀經驗。基於此結果,將來可以進一步做神經科學的探討。對於身體歸屬感與動作感二者的關係,我建議採用task-related functional connectivity的研究方法,這是我未來的研究方向。Recent studies of the rubber hand illusion (RHI) have shown that the sense of body ownership is constrained by several factors, yet is still very flexible. In order to increase our understanding, one significant aspect to consider is exactly how flexible our sense of body ownership really is. The distinction between “body-as-subject” and “body-as-object” in phenomenology forms a theoretical constraint regarding the sense of body ownership. According to this phenomenological constraint, a subject cannot experience his/her own body or body-parts both as-subject and as-object simultaneously. In this study, this issue is addressed by investigating the following questions: (1) Is it possible to have the illusion of owning four hands? and (2)Is it possible to experience body-as-subject and body-as-object at the same time? Using a head mounted display (HMD), the participant adopted the experimenter’s first-person perspective (1PP) as if it were his/her own. Sitting face to face, the participant saw either two or four hands—the experimenter’s two hands from the adopted 1PP and/or the subject’s own two hands in the opposite direction from an adopted third-person perspective (3PP)—being stroked synchronously or asynchronously. In an active four-handed condition, the participants were asked to tap their index fingers, while the experimenter imitated their movements. The result showed that in the passive two-hand condition, synchronous touching induced a variant of the RHI. In the passive four-hand condition, subjective tactile location could be dissociated from the sense of hand ownership. Strikingly, in the active condition, once all four hands began to act in the same pattern synchronously, many participants (68%) agreed or strongly agreed with the statement “I felt as if I had two more hands.” Supported by skin conductance response (SCR) measurements, these results show that the sense of body ownership is much more flexible than what most research has previously suggested. I investigate the “neurocognitive model of body ownership” proposed by Tsakiris (2010) in light of this study and argue that his model should be complemented by the involvement of the sense of agency and visual perspective, which were neglected completely in the previous model. Furthermore, a key component of the four-hand illusion provides an important counter-example against the distinction between body-as-object and body-as-subject. I try to show that it is possible for healthy participant to experience both body-as-subject and for body-as-object simultaneously. This behavioral study showed for the first time that it is possible to induce a “four-hand illusion” with healthy participants. Based on this result, further neuroscientific research is needed to discover the neural mechanism underpinning the sense of body ownership. I suggest that investigating Task-related functional connectivity will help determine the neural basis that underlies the relationship between a sense of body ownership and a sense of agency


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    Prevalence and Determinants of Workplace Violence of Health Care Workers in a Psychiatric Hospital in Taiwan

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    Workplace violence, a possible cause of job stress, has recently become an important concern in occupational health. This study determined the prevalence of workplace violence and its risk factors for employees at a psychiatric hospital in Taiwan. A questionnaire developed by ILO/ICN/WHO/ PSI was first translated and validated. It was then used to survey the prevalence of workplace violence in the last 12 months experienced by all nursing aides, nurses, and clerks at the hospital. Multiple logistic regression models were constructed to discover the determinants of violence. A total of 222 out of 231 surveyed workers completed a valid questionnaire. The one-year prevalence rates of physical violence (PV), verbal abuse, bullying/mobbing, sexual harassment, and racial harassment were 35.1, 50.9, 15.8, 9.5 , and 4.5%, respectively. The prevalence of PV at this hospital was higher than that reported by other countries for the health sector. A high anxiety level was associated with the occurrence of PV. These results need to be corroborated by future investigation. A training program may be required for high risk groups to reduce workplace violence
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