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.

关键词： carpal tunnel syndrome   electrodiagnosis   electromyography   nerve conduction study   neuromuscular ultrasound   personalized medicine   precision medicine  

摘要： See article on pages 661–667 in this issue.

摘要： This commentary is on the original article by Burgess et al. on pages 576–583 of this issue.

关键词： clinical genetics   ethics   genomics   informed consent   neurodevelopmental disorder   next generation sequencing   paediatric neurology   variant of uncertain significance  

摘要： Genetic tests are an efficient and effective diagnostic tool in paediatric neurology, and are increasingly incorporated into the diagnostic work-up of our patients. Significant advances in genetic technologies in recent years has expanded both the scale at which genetic testing can be done, and the speed with which results can be returned. However, there is no “perfect” genetic test which will identify all clinically relevant genetic variants. Understanding the appropriate application of each test type is therefore key to securing a diagnosis. It is vital that consent to genetic testing is freely given and adequately informed. In this article, using clinical vignettes, we will discuss the strengths and limitations of each genetic test, and give an overview of how to take informed consent. Our ability to identify variants has outstripped our ability to interpret them reliably so caution should be exercised. We describe the challenges of variant interpretation, and the importance of Clinical Genetics expertise in this process. © 2021 Elsevier Ltd