关键词： Severe dengue   Unusual manifestations   Sri Lanka   Serology   Molecular epidemiology  

摘要： Background: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities. Objectives: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed. Study design: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing. Results: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barre syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new Glade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan. Conclusions: The new Glade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.

关键词： Cockayne Syndrome   Rare disease   Animal model   Demyelination   Transcriptome   Xeroderma pigmentosum  

摘要： Although these approaches have yielded important information regarding the underlying disease mechanisms that can lead to a CS phenotype, they do not manifest the major features of CS neurologic disease seen in human patients. In particular, no myelin defects have been reported so far in any CS knockout mice, which stands in dramatic contrast to the severe myelination defects observed in human CS patients. However, in addition to these defects, histologic examination also demonstrated reduced myelination in the cerebellum, reminiscent of the myelination defects observed in human CS patients. Therefore, the myelination abnormalities reported by Xu et al. in Csb SP R571X sp rat are of potential translational importance, as they may allow for investigation into therapeutics for the myelin defects observed in human CS patients. [Extracted from the article]

关键词： Neurological disorders   Blood-brain barrier   Carbon dots   Sensing   Biocompatibility   Brain tumor  

摘要： The development of novel methods plays a fundamental role in early diagnosis and controlling of neurological disorders (NDs). Blood-brain barrier (BBB) is the most challenging barrier for the development of neuro drug delivery systems due to its inhibiting ability to enter drugs and agents into central nervous system (CNS). Carbon dots (CDs) have shown to be very promising and outstanding agents for various biomedical applications (bio imaging studies, treatment of NDs and brain tumors). They exhibit remarkable properties such as biocompatibility, small size (less than 10 nm, enabling penetration into BBB), tunable optical properties, photostability and simple synthetic procedures, allowing them to act as ideal candidates in various fields of science. Therefore, the objective of this review is to overview the recent studies on CDs for the development of neuro drug delivery systems to reach CNS via crossing of BBB. Primarily, this review briefly outlines the unique optical properties and toxicity of CDs. The development of novel neuro drug delivery systems for various neurological disorders using CDs as carriers is described. This review also covers the potential applications of CDs in brain tumors imaging and treatment of neurodegenerative diseases. Finally, the sensing applications and future prospects of CDs are summarized. (C) 2020 Elsevier B.V. All rights reserved.

关键词： Repetitive transcranial magnetic stimulation   cerebral ischemia   BDNF   RACK1   MeCP2 phosphorylation   neurological function  

摘要： Repetitive transcranial magnetic stimulation (rTMS) is acknowledged as a form of neurostimulation, especially for functional recovery. The foundational knowledge of molecular mechanism is limited regarding its role in cerebral ischemia, for which the present study was designed. Primary neurons were treated with oxygen-glucose deprivation (OGD) and repetitive magnetic stimulation (rMS), in which brain-derived neurotrophic factor (BDNF) and transcription ofBDNF exonswere examined. Then, adenovirus vectors carrying siRACK1 sequence were delivered to primary neurons, followed by detection of the transcription ofBDNF exonsand the extent of methyl CpG binding protein 2 (MeCP2) phosphorylation. Results showed that BDNF and the transcription ofBDNF exonswere upregulated by rMS and OGD treatment, but decreased by extra treatment of RACK1 siRNA. Then, the mechanism investigations demonstrated that rMS increased the extent of MeCP2 phosphorylation to promote the interaction between RACK1 andBDNF exon IV. The aforementioned findings were further confirmedin vivoin middle cerebral artery occlusion (MCAO)-induced rat models, as indicated by improved neurological functions and reduced area of cerebral infarction. The study offers potential evidence for improvement of neurological deficits, highlighting the important role of rTMS for treatment of cerebral ischemia.

关键词： 7p22.3 deletion   Mosaic deletion   SNX8   Tetralogy of fallot  

摘要： Some cases of chromosome 7p22.3 deletions have been reported, but the genotype-phenotype correlation is still uncertain. Neurodevelopmental delay and heart anomalies have been recorded as the most recurrent defects. We describe the clinical features of a four-year-old male child with a 139 kb deletion at 7p22.3 involving SNX8 gene, inherited from a mosaic mother. The same deletion is also present in the fetus on the ongoing third pregnancy of the couple with normal fetal ultrasound assessment. The proband was prenatally diagnosed with left kidney agenesis. He does not show any congenital heart disease, but mild intellectual disability, learning and language delay, and severe behavioral problems related to the hyperactive-impulsive and inattentive area. These clinical features are also evident in other 7p22 deletions cases involving the SNX8 gene, supporting the role of this gene in neurodevelopment. Conversely, the revision of all published cases with small 7p22 deletions and the absence of heart malformations in the present family confirm that this region is involved in heart development, anyway did not confirm the role of SNX8 in cardiac phenotypes, either due to the reduced penetrance or the involvement of other candidate genes.

摘要： How can neurology be affected by the '100 Radical Innovation Breakthroughs for the Future' report of the European Commission? Horizon 2020 and Horizon Europe are two ambitious programmes of the European Union for research and innovation. The European Commission conducted an extensive automated survey of scientific and technical literature, filtered by panels of experts, as part of the preparation for Horizon Europe's implementation. [Extracted from the article]

关键词： copper   cellular bioimaging   neurodegenerative diseases   copper-related disorders   SIMS techniques   TEM   S-XRF  

摘要： As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer's disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.

关键词： Letter of recommendation   Neurosurgery residency match   Standardized letter of evaluation  

摘要： BACKGROUND: The letter of recommendation (LOR) represents a nonstandardized way to evaluate residency candidates. The goal of this project was to assess the current components of the Electronic Residency Application Service application and to determine and develop support for a standardized letter of evaluation (SLOE) in the resident selection process. METHODS: A 16-question survey was sent to US neurosurgery program directors. In addition to demographic information, respondents were asked to rank 7 aspects of the current application (1-7), evaluate the inclusion of specific standardized questions about applicants (yes or no), note their agreement with statements about LORs (on a 5-point Likert scale), and provide any additional comments. RESULTS: Fifty-three of 113 program directors (47%) completed the survey. The interview (average rank, 2.0 +/- 1.4), United States Medical Licensing Exam step 1 score (2.86 +/- 1.4), and LOR (2.96 +/- 1.5) were ranked as the most important aspects of the application. Agreement was high for items regarding the utility of the current LOR (51%-78% agreement). Almost two-thirds (65%) of program directors agreed that implementing a standardized LOR would improve the resident selection process. Inclusion of questions regarding applicants' work ethic, teamwork, communication, professionalism, and initiative were strongly supported (>80% in favor), whereas including a question on theoretical rank position was mixed (54%). CONCLUSIONS: Most neurosurgical program directors agree that increasing the objectivity of the application would be beneficial, including the addition of standardized questions. However, there is only moderate interest in implementing an SLOE.

关键词： cerebral palsy   dysphagia   gastroesophageal reflux   nutritional status   quality of life  

摘要： Objectives:Total oesophagogastric dissociation (TOGD) is an alternative antireflux surgery for neurologically impaired children because of a 16% to 38% fundoplication failure rate. This study evaluates TOGD's feasibility and its long-term efficacy both as a Primary and as a "Rescue" procedure after failed ***:Thirty patients (18 boys) who underwent TOGD between 2000 and 2018 in 2 Italian Centres were retrospectively reviewed. Twenty-three were Primary procedures and 7 were "Rescue" ones. Inclusion criteria were severe neurodisability, intractable gastroesophageal reflux, and ***:Preoperatively, all children had regurgitation, vomiting or retching, and 93% had unsafe swallowing and aspiration, with recurrent chest infections/aspiration pneumonia. Median relative weight was 77% (48%--118%). All patients were taking antireflux medication before surgery. Median age at TOGD was 6.48 years (0.69--22.18). Median follow-up was 3.5 years (0.6-17.7). No recurrence of gastroesophageal reflux (GER) and vomiting was recorded. The number of chest infections and length of hospital stay showed a significative decrease (P value <0.0001 for both), whereas median relative weight reached 101% (P value 0.002). Parents'/caregivers' perception of outcome showed a significative improvement. Six patients (20%) experienced early complications and 3 required surgical intervention. Three late complications (10%) also required surgery. There was no surgery-related ***:TOGD is an effective procedure with an acceptably low complication rate for children with severe neurological impairment and is followed by a major improvement in general health and quality of life for children and families. There was no substantial difference in outcome between Primary and "Rescue" procedures.

关键词： Hypoxia   Sleep-disordered breathing   Cognition   Academic achievements  

摘要： This review looks at data on potential associations between intermittent hypoxia (IH) and impaired neurodevelopment in infants and children. In extremely preterm infants (< 28 wk gestation), such an association has been established based on a secondary analysis of Canadian Oxygen Trial data. These showed, in 997 infants, that the odds of developing cognitive or language impairment at 18 months corrected age were 3 times higher in infants who were in the highest decile for %time spent with events where pulse oximeter saturation (SpO(2)) was < 80% for >1 min during their first 10 postnatal weeks compared to those who had very few such events after birth. In older term and preterm infants, the occurrence of 5 or more events with prolonged apnea and bradycardia during home monitoring was associated with 5 points less on the mental development index of the Bayley-II scales. For older children, associations between sleep-disordered breathing and impaired cognition/academic achievements have also been established, but not consistently, and it remains unclear whether this association is primarily mediated via IH or via sleep deprivation. Animal data show that IH may cause apoptosis particularly in the hippocampus. Although we need to stress that associations cannot prove causality, current evidence provides support for IH to be detected and prevented early. Future studies should focus on IH rather than on apnea/bradycardia.