Loss of mitochondrial ClpP,Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease

neurogenetics - Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory...     

Schwangerschaft. Fehlgeburt. Geburt. Kindesmord

Ohne Zusammenfassung     

Contributions and limitations of the cognitive neuropsychological approach to treatment: Illustrations from studies of reading and spelling therapy

Background : Cognitive neuropsychological research is focused on improving the understanding of cognitive processes and representations underlying normal tasks such as reading and spelling, on the basis of impaired performance of these tasks after brain damage. Functional architectures of cognitive tasks developed through this approach have often assisted speech-language pathologists and other therapists in understanding the task to be treated, and in identifying the impaired and spared components of the task to be treated in each individual with brain damage. Aims : To review the benefits and limitations of this approach, focusing on illustrations from treatment of reading and spelling, and to provide ideas about how the limitations might be addressed. Contributions : We provide examples that demonstrate how disruption of particular cognitive functions in the process of reading or spelling might be identified and rationally treated. Additionally, we provide some illustrations of how limitations of this approach might be addressed by considering evidence from cognitive neuroscience regarding neural mechanisms of recovery and learning. Conclusions : Insights from cognitive neuropsychology should be integrated with insights from neuroscience in developing rehabilitation strategies.     

Mechanisms of early aphasia recovery

Background: The course of recovery of aphasia after stroke is highly variable. Some patients, even with severe aphasia, recover rapidly over the first days after onset. The mechanism of this early recovery (and later recovery) is unclear. Plausible accounts include reperfusion of ischaemic tissue surrounding the stroke, and rapid reorganisation of structure/function relationships. Aims: Based on a recent study showing that the severity of word comprehension impairment in acute stroke patients is strongly correlated with the severity of hypoperfusion (low blood flow) in Wernicke's area, we hypothesised that early recovery of spoken word comprehension is due to reperfusion (restored blood flow) to Wernicke's area. Our objective was to evluate this hypothesis using advanced magnetic resonance imaging techniques of perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Methods and Procedures: A series of 100 patients with acute, left hemisphere ischaemic stroke were evaluated within 24 hours of onset or worsening of symptoms, and 3 days later, using PWI, DWI, and a battery of lexical tasks, including spoken word/picture verification. A subset of 18 patients with impaired spoken word comprehension at Day 1 were included in the study. Chi square analysis was used to identify the association between early recovery of spoken word comprehension and reperfusion of each of 10 Brodmann's areas (BA). Outcomes & Results: Early recovery of spoken word comprehension was significantly associated with reperfusion of BA 22 (Wernicke's area), but not with reperfusion of other BAs. All patients who showed early recovery of word comprehension also showed reperfusion of Wernicke's area, due to carotid endarterectomy, carotid stenting, induced blood pressure elevation, or spontaneous reperfusion. Conclusions: Tissue recovery, brought about by restored blood pressure elevation, likely accounts for cases of rapid resolution of aphasia in the first few days of stroke. Other mechanisms of recovery, including reorganisation of structure/function relationships, and learning of compensatory strategies, are likely important in later stages of recovery.     

Prevention of bronchiolitis obliterans in rat lung allografts by type V collagen-induced oral tolerance

BACKGROUND: We have reported that feeding type V collagen (col(V)) to lung allograft recipients induces immune tolerance that prevents acute lung allograft rejection. Repeated acute rejection is a risk factor for or associated with chronic rejection, known as bronchiolitis obliterans (BO), the leading cause of death in lung allograft recipients. The current study examines if col(V)-induced oral tolerance prevents BO. METHODS: WKY rats (RT1l) were fed either col(V) or diluent before orthotopic transplantation of F344 (RT1lvl) lung allografts. No rats received any immunosuppression. At 10 weeks posttransplantation the time to onset of BO, delayed type hypersensitivity (DTH) responses to donor antigens, and col(V) were examined. In addition, proliferative responses of recipient T lymphocytes to donor antigens, and ability of recipient antigen presenting cells to present alloantigens in lung allografts were evaluated. RESULTS: The data show that recipient rats have sustained DTH responses to donor antigens and col(V). T lymphocytes from col(V)-fed lung allograft recipients were unable to proliferate in response to donor antigens, but feeding col(V) had no effect on the presentation of donor alloantigens by recipient antigen presenting cells. All diluent fed rats developed BO, but only mild acute rejection (grade 2) was present in all rats fed col(V). Transforming growth factor (TGF)-beta production was up-regulated systemically in col(V)-fed, but not diluent fed, lung allograft recipients, and neutralizing TGF-beta [corrected] recovered the DTH response to donor antigens in col(V)-fed rats. CONCLUSIONS: Collectively these data show that col(V)-induces oral tolerance that prevents BO, and that tolerance may be mediated by systemic production of TGF-beta [corrected].     

Ergebnisse und Komplikationen nach urethralen Bändern

Zusammenfassung Der Einsatz der urethralen Bänder entspricht dem Trend der Zeit und kann aufgrund der Datenlage bei entsprechender Indikationsstellung befürwortet werden. Der transobturatorische Zugang scheint gegenüber dem retropubischen Zugang im Hinblick auf die intraoperativen Komplikationen Vorteile zu bringen. Die häufigste postoperative Komplikation stellt bei beiden Verfahren die zu enge Bandlage dar. Daher ist auf diesen Umstand intraoperativ besondere Aufmerksamkeit zu lenken.     

The crucial role of posterior frontal regions in modality specific components of the spelling process

Although it is commonly assumed that posterior temporo-parietal regions are the regions of the brain essential for accessing orthographic representations for written output, patients with lesions in these areas also have reading and/or naming impairments at least early after stroke onset. This observation raises the possibility that these regions are important for components of spelling that are not specific to written output. The goal of the present study was to identify any regions of the brain that, when damaged, result in selective impairment in accessing orthographic representations for written output. We studied 54 consecutive right-handed patients with acute, left hemisphere ischemic stroke, who were barely able to perform the motor aspects of writing with the right hand and had at least 10th grade education, on a battery of lexical tasks designed to identify impaired and spared cognitive processes underlying spelling and with advanced magnetic resonance imaging. Only five patients had pure agraphia, and had evidence of impaired access to lexical-orthographic representations for output; and all five had infarct or ischemia in Brodmann's area 44 and 45. Analysis of performance across tasks of three of these patients, whose performance has not been previously reported, provides evidence for additional impairment in converting graphemes to letter shapes or letter-specific motor programs. These three patients, unlike previously reported patients with lexical-orthographic impairment and compromised function in Brodmann's area 44 and 45, also had infarcts in Brodmann's area 6. On the basis of these cases, and those in the literature, we propose a network of brain regions involved in writing words, each with a separate function. This proposal emphasizes the role of the left posterior frontal regions in modality-specific output processes.     

A neural network critical for spelling

We aimed to identify neuroanatomical regions associated with deficits to the graphemic buffer, a working memory component of the spelling system that holds the sequence of letter identities during production. We evaluated 331 patients with left hemisphere ischemic stroke with various spelling tests and magnetic resonance diffusion‐weighted imaging and perfusion‐weighted imaging, within 48 hours of stroke onset. A voxel‐wise statistical map showed that ischemia in voxels in posterior and inferior frontal and parietal cortex, subcortical white matter underlying prefrontal cortex, lateral occipital gyrus, or caudate was associated with impairment in maintaining the sequence of letter identities while spelling. Ann Neurol 2009;66:249–253