关键词： Blastocyst complementation   Chimera   Stem cells   Cell transplantation   Cognition   Behavior  

摘要： Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered preimplantation animal embryos eventually giving rise to fully developed human tissues and organs within the animal host for use in regenerative medicine. The ethical issues surrounding this method have caused the National Institutes of Health to issue a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal. To address this concern, we performed an in-depth review of the neural transplantation literature to determine how the integration of human cells into the nonhuman neural circuitry has altered the behavior of the host. Despite reports of widespread integration of human cell transplants, our review of 150 transplantation studies found no evidence suggestive of humanization of the animal host, and we thus conclude that, at present, concerns over humanization should not prevent research on blastocyst complementation to continue. We suggest proceeding in a controlled and transparent manner, however, and include recommendations for future research with careful consideration for how human cells may contribute to the animal host nervous system. Stem Cells2019;37:444-452

关键词： CARDIOGENIC shock   EXTRACORPOREAL membrane oxygenation  

摘要： Purpose Neurological complications (NC) are potentially devastating for cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The purpose of this study was to investigate the overall incidence and pattern of NC and their impact on *** We retrospectively reviewed 498 consecutive patients who received VA-ECMO support for cardiogenic shock between March 2007 and May 2018. Information on NC type, including stroke, altered mental status, seizure, encephalopathy, and transient ischemic attack and other neurological events was collected. Survival to discharge was compared between patients with and without neurological *** Median age of the entire cohort was 60 years (IQR 49-68), and 69% were male. Etiology of cardiogenic shock included post-cardiotomy shock (n=154, 33%), acute myocardial infarction (n=124, 27%), post-transplant graft failure (n=60, 13%), acute decompensated heart failure (n=65, 14%), and others (n=57, 12%). Eighty-seven patients were cannulated via the ascending aorta (18%), 37 via the axillary artery (7%), and 374 (75%) via the femoral artery. In total, 125 patients (25%) were diagnosed with NC: altered mental status was most common n=62 (12%), stroke n=29 (6%), encephalopathy n=16 (3%), seizure n=15 (3%), transient ischemic attack/others n=16 (3%). NC diagnosis was significantly associated with higher in-hospital mortality rates (74%, n=93) vs. non-NC diagnosis (61%, n=229), (p=0.008). Among NC subtypes, encephalopathy had the highest in-hospital mortality rate (94%, n=15), followed by stroke (72%, n=21) and AMS (71%, n=44).Conclusion Neurological disorders are common in cardiogenic shock patients who receive VA-ECMO and significantly impact in-hospital mortality rates.

关键词： avian bornavirus   neurological signs   feather-damaging behaviour  

摘要： Parrot bornaviruses (PaBV) are the causative agents of proventricular dilatation disease in psittacine birds, but have also been linked to other clinical signs, including behavioural disorders and neurological signs. The aim of this study was to correlate PaBV infection in birds showing feather-damaging behaviour or neurological signs for which no other cause of disease could be identified. Psittacine birds presented to a private practice were divided into three groups: birds with neurological signs (n = 28), birds showing feather-damaging behaviour (n = 42) and birds presented for routine examinations (n = 56). Swabs of crop and cloaca were collected and investigated for the presence of PaBV-RNA using real time RT-PCR. Additionally, serum samples were taken and examined for the presence of anti-PaBV antibodies by immunofluorescence test. PaBV infection was detected in one of the test systems in 40.5 per cent of all birds (n = 126) investigated. In the clinically healthy birds (n = 56), 19.6 per cent of the birds were positive in at least one of the PaBV tests, compared with 52.38 per cent of the feather-damaging (n = 42) and 64.28 per cent of the neurologically diseased birds (n = 28). Interestingly, the anti-PaBV antibody titres in birds with neurological signs were highest up to 1: 20480. High antibody titres (up to 1: 5120) were also found in the feather-damaging group, whereas the birds of the control group, if PaBV positive, had only very low titres. Similarly, the highest viral load was found in the group of the neurologically diseased birds, followed by feather-damaging birds, whereas PaBV-positive birds in the control group demonstrated only low viral RNA shedding. A clear correlation between severity of clinical signs, amount of viral shedding and high levels of antibody titres was observed for most of the neurologically diseased birds and also for few birds with feather-damaging behaviour. For the first time, these results clearly indicate a correlation b

关键词： PEG-600   Imidacloprid   Histopathology   Neuroalterations   Neurotransmitters Japanese quails  

摘要： Agrochemical risk assessment that takes into account only pesticide active ingredients without the spray adjuvants will miss important toxicity outcomes detrimental to non-target species including birds. In the present study toxicity of imidacloprid (IMI) pesticide was evaluated individually and in a mixture with polyethylene glycol (PEG-600) as adjuvant against Japanese quails. Oral intubation was used to obtain concentration-mortality data. Oral intubation was used to obtain concentration-mortality data. Treatments of quails for 24h with different doses leading to the calculation of LC50 values. PEG enhances the pesticide efficacy and the LD50 value of IMI was 17.02mg/Kg(1), and in combination with PEG it was 15.98mg/kg(-1). In the second phase of the study, the effects of a single acute dose of IMI (1/4 LD50) individually or in a mixture with PEG has a potent effect on the activity of plasma AChE and brain monoamines transmitters. However, the addition of PEG-adjuvant to the selected insecticide has shown more toxic potential, more highly significant decreases in AChE activity and different changes in cortical monoamines concentration. In the present study the maximum significant inhibition of AChE activity, was recorded post 72h exposure to IMI individually and 96h in a mixture with PEG and exhibited -37.56% and -32.65% decreases, respectively. Moreover, the oral intubation of IMI individually or in a mixture with PEG caused a significant elevation in the quail cortical NE and 5-HT. The result also showed while the mixture of IMI+PEG induced the more potent effect in DA alterations, IMI individually was more effective in 5-HT changes. Our findings also indicated that PEG exposure induced remarkable changes in the studied monoamines level and the values were significant throughout the tested periods in DA. Moreover, the studied dose level was vigorously affected quail brain cerebral cortex histological structure. When administered individually or in a mixture wit

关键词： Brain injuries   Regeneration and repair in the nervous system   Stroke   Therapeutics  

摘要： Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodelling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodelling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy.

关键词： Anti-Hu antibody   cancer biomarker   CRMP5 antibody   GABA(B) receptor antibody   paraneoplastic syndrome  

摘要： Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC-predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%;the median age at diagnosis was 64years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti-neuronal nuclear antibody-type 1, voltage-gated calcium channel (VGCC)-N-type, VGCC-P/Q-type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR);while the most common in patients without neurological manifestations were: GAD65, muscle-AChR, and VGCC-P/Q-type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody-positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited-stage disease at diagnosis.

关键词： CT perfusion   early neurological deterioration   lenticulostriate artery   MR perfusion   perfusion   stroke   territory  

摘要： Background Early neurological deterioration occurs in approximately 10% acute ischemic stroke patients after thrombolysis. Over half of the early neurological deterioration occurred without known causes and is called unexplained early neurological deterioration. Aims We aimed to explore the development of early neurological deterioration at 24 h after thrombolysis, and whether it could be predicted by the presence of baseline hypoperfusion in lenticulostriate arteries territory in acute ischemic stroke patients. Methods We retrospectively reviewed our prospectively collected database of acute ischemic stroke patients in the unilateral middle cerebral artery territory who had baseline perfusion image and received thrombolysis. Unexplained early neurological deterioration was defined as >= 2 points increase of National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 h, without known causes. Hypoperfusion lesions in different territories were identified on perfusion maps. Results A total of 306 patients were included in analysis. Patients with pure lenticulostriate arteries hypoperfusion (defined as the presence of hypoperfusion in lenticulostriate artery territory, but not in middle cerebral artery terminal branch territory) were more likely to have unexplained early neurological deterioration than others (27.6% vs. 6.1%;OR, 5.974;p = 0.001), after adjusting for age, baseline NIHSS and onset to treatment time. Conclusions Patients presenting hypoperfusion in pure lenticulostriate arteries territory were easier to experience unexplained early neurological deterioration.

摘要： "Comparison of clinical features in transient focal neurological episodes between hereditary transthyretin type and Aβ type cerebral amyloid angiopathy."Amyloid, 26(sup1), pp. 81–82

关键词： Rho GTPases   GAPs   GEFs   axon guidance   neurological diseases   central nervous system  

摘要： One of the fundamental steps during development of the nervous system is the formation of proper connections between neurons and their target cells-a process called neural wiring, failure of which causes neurological disorders ranging from autism to Down's syndrome. Axons navigate through the complex environment of a developing embryo toward their targets, which can be far away from their cell bodies. Successful implementation of neuronal wiring, which is crucial for fulfillment of all behavioral functions, is achieved through an intimate interplay between axon guidance and neural activity. In this review, our focus will be on axon pathfinding and the implication of some of its downstream molecular components in neurological disorders. More precisely, we will talk about axon guidance and the molecules implicated in this process. After, we will briefly review the Rho family of small GTPases, their regulators, and their involvement in downstream signaling pathways of the axon guidance cues/receptor complexes. We will then proceed to the final and main part of this review, where we will thoroughly comment on the implication of the regulators for Rho GTPases-GEFs (Guanine nucleotide Exchange Factors) and GAPs (GTPase-activating Proteins)-in neurological diseases and disorders.

关键词： Quality of life   Newborns at neurological risk   Follow-up   Neurological outcome   Neuro-evolutionary development  

摘要： BackgroundIn order to give a new contribution to the knowledge of the psycho-physical, behavioral and socio-relational development of the individuals who were born at neurological risk, we have carried out a research work through a retrospective and observational analysis in such people, followed in their neuro-evolutionary development from the Department of Pediatrics and Neonatology of the Hospital of *** purpose of this work is to value the quality of life of the individuals born at neurological risk at a distance of time from the *** the literature only recently there are studies on the quality of life of some categories of people, but survey does not seem to be performed in individuals previously born at neurological *** statistical descriptive and inferential survey has been carried out on 812 individuals who were born at neurological risk, 442 preterm newborns and 370 term newborns, followed from 1977 until to 2007. They were classed in order to their age at the time of our observation. We have submitted the entire sample to a Questionnaire to investigate some areas of their life, ranging from their clinical and psycho-social history to their personal coming of life. Then the same persons, subdivided according to the various age groups, were subjected to other Questionnaires on the quality of life, internationally *** outcomes were found in 14.7% of the preterm newborns and in 6% of the term newborns, with a significant correlation between neurological outcomes and gestational age, low birth-weight, hypoxic-ischemic encephalopathy and low APGAR-index. Neuro-disabilities were found prevalently belong to the small for gestational age preterm newborns. A low quality of life emerged in those who had neurological *** study on the individuals who were born at neurological risk, analyzed at a distance, shows that a good health is associated with a good quality of life, while a low quality of life occurs to