关键词： Stem cells   Mesenchymal stem cells   Neuronal cells   Transdifferentiation  

摘要： Neurodegenerative disorders have become the leading cause of chronic pain and death. Treatments available are not sufficient to help the patients as they only alleviate the symptoms and not the cause. In this regard, stem cells therapy has emerged as an upcoming option for the replacement of dead and damaged neurons. Stem cells, in general, are characterized as cells exhibiting potency properties, i.e., on being subjected to specific conditions they transform into cells of another lineage. Of all the types, mesenchymal stem cells (MSCs) are known for their pluripotent nature without the obstacle of ethical concern surrounding the procurement of other cell types. Although fibroblasts are quite similar to MSCs morphologically, certain markers like CD73, CD 90 are specific to MSCs, making both the cell types distinguishable from each other. This is implemented while procuring MSCs from a plethora of sources like umbilical cord blood, adipose tissue, bone marrow, etc. Among these, bone marrow MSCs are the most widely used type for neural regeneration. Neural regeneration is achieved via transdifferentiation. Several studies have either transplanted the stem cells into rodent models or have carried out transdifferentiation in vitro. The process involves a combination of growth factors, pre-treatment factors, and neuronal differentiation inducing mediums. The results obtained are characterized by neuron-like morphology, expression of markers, along with electrophysical activity in some. Recent attempts involve exploring biomaterials that may mimic the native ECM and therefore can be directly introduced at the site of interest. The review gives a brief description of MSCs, their sources and markers, and the different attempts that have been made towards achieving the goal of differentiating MSCs into neurons.

关键词： antiepileptic medication   dog   quality of life   veterinary neurology  

摘要： Background Epilepsy is the most common chronic neurological disease in dogs that adversely affects the quality of life (QoL) of affected dogs and their owners. Research on epilepsy in dogs is expanding internationally, but where best to focus limited research time, funds, and expertise to achieve better outcomes for affected dogs and their owners has not been studied. Objective To explore idiopathic epilepsy (IE) research priorities of owners of dogs with IE, general practice veterinarians, and veterinary neurologists. Methods An international online survey was conducted in 2016 and repeated in 2020. Participants rated the absolute importance and relative rank of 18 areas of IE research, which were compared between groups and time points. Results Valid responses were received from 414 respondents in 2016 and 414 respondents in 2020. The development of new anti-seizure drugs (ASD) and improving the existing ASD management were considered the most important research priorities. Areas of research with increasing priority between 2016 and 2020 included non-ASD management, with the greatest potential seen in behavioral and dietary-based interventions. Disagreements in priorities were identified between groups;owners prioritized issues that impacted their and their dog's QoL, for example, adverse effects and comorbidities, whereas general practitioner vets and neurologists prioritized clinical issues and longer-term strategies to manage or prevent IE, respectively. Conclusions and Clinical Importance Ensuring that voices of owners are heard in the planning of future research should be a broader goal of veterinary medicine, to target research efforts toward areas most likely to improve the QoL of the dog-owner dyad.

关键词： Adherence   Quality of life   Non-adherence   Neurological disorders   Chronic diseases  

摘要： Background/Aim: Medication non-adherence may cause significant morbidity and mortality in patients with chronic diseases and may increase the economic burden on the healthcare system. The prevalence of neurological disorders is increasing in Malaysia;however, comprehensive data on medication adherence among Malaysian patients with these disorders is limited. This study was conducted to determine the association of medication non-adherence with quality of life in patients with neurological problems. Methods: A cross-sectional survey was performed in 370 patients diagnosed with epilepsy, Parkinson's disease, stroke and Alzheimer's disease at Neurology clinic. Patients aged 18 years or older, without documented physical or psychiatric illness such as schizophrenia and major depression, were included. Patient-administered questionnaires, such as the Malaysian Medication Adherence Scale and Medication Possession Ratio were used to determine medication adherence. An established EQ-5D-3L questionnaire was used to determine quality of life. Data were analysed using descriptive and inferential analysis. Results: The overall prevalence of medication non-adherence among patients with neurological disorders was 59.2%. Among these neuromedical diseases, 69.2% (n = 9/13) of Alzheimer's disease, 66.7% (n = 98/147) of epilepsy, 62.1% (n = 36/58) of Parkinson's disease and 48.7% (n = 74/152) of stroke patients were found non-adherent. There was a significant difference in EQ-5D index scores (p = 0.041) between adherent and non-adherent patients. Conclusion: A high prevalence of medication non-adherence was found among patients with neurological disorders. The rate of non-adherence varied among different neurological conditions. There was a significant difference in quality of life between adherent and non-adherent patients. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creative

关键词： Neurologic emergencies   Anesthetic pharmacology   Airway management   Endotracheal intubation   Ventilation   Sedation  

摘要： Airway obstruction and respiratory failure are common complications of neurological emergencies. Anesthesia is often employed for airway management, surgical and endovascular interventions or in the intensive care units in patients with altered mental status or those requiring burst suppression. This article provides a summary of the unique airway management and anesthesia considerations and controversies for neurologic emergencies in general, as well as for specific commonly encountered conditions: elevated intracranial pressure, neuromuscular respiratory failure, acute ischemic stroke, and acute cervical spinal cord injury.

关键词： Brain organoid   Myotonic dystrophy type 1   Neural stem cell  

关键词： inflammatory response   ischaemia   reperfusion injury   tenacissoside H   TrkB  

摘要： Cerebral ischaemia/reperfusion (I/R)-induced acute brain injury remains a troublesome condition in clinical practice. The present study aimed to investigate the protective effect of tenacissoside H (TH) on I/R-induced cerebral injury in mice. Here, a mouse model of middle cerebral artery occlusion (MCAO) was established by an improved Longa-Zea method. TH was given by intraperitoneal injection once a day within 1 week before establishing the mouse MCAO model. The neurological functions of mice were evaluated and the apoptosis of neurons was also detected by the TUNEL method and Nissl's staining. ELISA and western blot were used to detect the expression of inflammatory factors, oxidation factors and proteins in the cerebral ischaemic cortex. The results revealed that TH dose-dependently reduced neurological impairment, neuron apoptosis and brain oedema induced by MCAO. Furthermore, TH attenuated the expression of pro-inflammatory cytokines (including interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha), iNOS and nuclear factor (NF)-kappa B while increased production of anti-inflammatory cytokines (IL-4, IL-10 and BDNF) and proteins of tropomyosin-related kinase receptor B (TrkB) and PPAR gamma. Nevertheless, after the addition of TrkB inhibitor, the effects of TH above were mostly restrained. In conclusion, TH can protect mice against I/R-induced neurological impairments via modulating inflammation and oxidative stress through TrkB signalling.

关键词： SARS-CoV2   COVID-19   Genetic diversity   Climatic factors   Neurological disorders  

摘要： The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.

关键词： CRYAB   Whole exome sequencing   Crystallinopathy   CNS involvement  

摘要： We report a multiplex family with extended multisystem neurological phenotype associated with a CRYAB variant. Two affected siblings were evaluated with whole exome sequencing, muscle biopsy, laser microdissection, and mass spectrometry-based proteomic analysis. Both patients and their mother manifested a combination of early-onset cataracts, cardiomyopathy, cerebellar ataxia, optic atrophy, cognitive impairment, and myopathy. Whole exome sequencing identified a heterozygous c.458C>T variant mapped to the C-terminal extension domain of the Alpha-crystallin B chain, disrupting its function as a molecular chaperone and its ability to suppress protein aggregation. In accordance with the molecular findings, muscle biopsies revealed subsarcolemmal deposits that appeared dark with H&E and trichrome staining were negative for the other routine histochemical staining and for amyloid with the Congo-red stain. Electron microscopy demonstrated that the deposits were composed of numerous parallel fibrils. Laser microdissection and mass spectrometry-based proteomic analysis revealed that the inclusions are almost exclusively composed of crystallized chaperones/heat shock proteins. Moreover, a structural model suggests that Ser153 could be involved in monomer stabilization, dimer association, and possible binding of partner proteins. We propose that our report potentially expands the complex phenotypic spectrum of alpha B-crystallinopathies with possible effect of a CRYAB variant on the central nervous system.

关键词： Paraneoplastic neurological syndromes   Cytotoxic immune response   Granzyme B   Ovarian cancer   Lung cancer  

摘要： BackgroundParaneoplastic neurological syndromes (PNS) may coexist with ovarian or lung cancers. Some tumors coexisting with PNS are smaller and have a better prognosis than tumors without PNS. PNS may constitute an opportunity to observe a natural immune antitumor response. We aimed to investigate a cytotoxic immune response by measuring granzyme B (GrB) in peripheral blood mononuclear cells (PBMC) in patients affected with ovarian or lung malignancy, with and without accompanying *** enrolled patients with: nonmalignant lesions (n=21), ovarian cancer (n=19), lung cancer (n=57), and PNS (n=30). PBMC were isolated by density gradient centrifugation with Ficoll-Paque. We evaluated the expression of GrB in PBMC lysates by ELISA and normalized to protein content as measured by the Lowry *** levels in PBMC in the group with malignant tumors-median 1650 pg/mg protein (interquartile range 663-3260 pg/mg) and in patients with PNS-median 1890 pg/mg protein (range 1290-2640 pg/mg) was lower than in control group with nonmalignant lesions-median 5240 pg/mg protein (range 2160-7440 pg/mg), p=0.0003 and p=0.0038, respectively. The differences in GrB levels in PBMC between these groups were independent of epidemiological factors-age, sex, body mass index (BMI), and the number of immune cells, as confirmed by multiple regression analysis. Within the group of patients with malignancy and PNS, GrB levels in PBMC were elevated if onconeural antibodies were detected (2610;2390-3700 pg/mg protein) as compared to patients without antibodies (1680;970-1880 pg/mg protein, p=0.035). GrB in PBMC was higher if the malignancy was diagnosed at the low (3060;2120-5220 pg/mg protein) as compared to the high stage (1330;348-2140, p=0.00048). In patients with lung cancer, the expression of GrB in PBMC was lower (1430;635-2660 pg/mg protein) than in the group with ovarian cancer (2580;1730-3730, p=0.02).ConclusionThe cytotoxic response measured in peripheral blood by GrB in

关键词： clinical research   Germany   good clinical practice   survey  

摘要： Background and purpose To provide an overview on the status of clinical research in neurology in Germany. Methods German university hospitals, nonuniversity hospitals, and neurological medical practices were surveyed regarding their clinical research activities during the period 2013 to 2017. Results Fifty percent of university hospitals, 10.6% of nonuniversity hospitals, and 5.2% of medical practices in Germany responded to our questionnaire. More than 80% of the clinical studies conducted have been phase III/IV and noninterventional trials (NISs), whereas <1% have been phase I and 3.5% investigator-initiated trials (IITs). University hospitals have conducted most of the phase II-IV trials. NISs have been predominantly performed by medical practices. Fifty-six percent of the university hospitals and less of the nonuniversity institutions confirmed the implementation of standard operating procedures (SOPs). In university hospitals, on average, 11 physicians had acquired a good clinical practice certificate. Overall, 43% of all trials have been performed in neuroimmunology. Conclusions The status of clinical research in neurology in Germany is predominated by NISs and late-phase trials, potentially due to a general lack of easily accessible funding, which leads to a highly competitive environment and fewer opportunities to perform early-phase clinical trials as well as IITs. Our results indicate that there is substantial need for structured support for creating and implementing SOPs to maintain quality standards and guarantee uniformity of performance. This survey assessed many aspects of clinical research and serves as guidance for providing ideas for structured improvement of clinical research in neurology in Germany.