关键词： Laparoscopic surgery   Liver retraction methods   Needle grasper   Crural suture   Children  

摘要： Aim of the study Liver retraction during laparoscopic fundoplication is important for obtaining an optimal space. Several methods have been developed, but the risks and benefits are unclear. We compared three different approaches and evaluated their safety and utility. Methods Forty-three neurologically impaired patients who underwent laparoscopic fundoplication between 2005 and 2018 were classified into three groups: A, snake retractor method, n = 18;B, crural suture method, n = 13;C, needle grasper method, n = 12. Patients' characteristics and outcomes were reviewed. Main results The liver retraction time was significantly shorter in group C than in A or B (p < 0.05). The operative times were shorter in groups B and C than in A. There were no significant differences in the liver enzyme levels. The liver enzyme levels increased temporarily but improved within a week. The C-reactive protein levels were significantly lower in group B than in A or C (p < 0.05). Conclusions The most convenient method was the needle grasper method, as the other two approaches create conflict with the operator's forceps. The crural suture method damages the liver less, but requires higher surgical skill levels. It is important to select the appropriate method according to the operator's skill and the patient's size and deformity.

关键词： Serious game   Physical rehabilitation   Computer vision   Neurological diseases   Motivation  

摘要： Objective: Being aware that serious games can be an interesting and appealing tool, the objective of this paper is to present the Physioland, a serious game based on image processing techniques, developed to monitor the physical therapy practice of patients with reduced mobility as a consequence of neurological disease. Materials and Methods: Several tests were performed in a clinical environment. The system stores every second the data relative to alignment, compensation and speed of the patient while he/she performs each exercise. The sample consisted of eleven elements aged from 17 years to 83 years, with neurological diseases in a mild or moderate state, with sequelae such as hemiparesis, paraparesis, hemidystonia, cerebellar syndrome and hemihyposthesia. Each patient used the game in twice a week in sessions of physical therapy, with the duration of about thirty minutes, for twelve to fifteen sessions. In each session, the patient performed several challenges, for two and a half minutes or five minutes each, according to his/her physiotherapeutic plan. Results: All the patients suffered oscillations in their behavior, but with better or worse performances, higher or lower scores, they were able to successfully complete the different exercises provided by Physioland, which are part of their physiotherapeutic plans. Conclusion: Based on the results obtained it can be said that it was possible to adapt specific exercises of traditional physical therapy to situations of electronic game, reason why Physioland fulfills the objective of monitoring the practice of physical therapy of patients with reduced mobility as a consequence of neurological disease.

关键词： CasRx   Ptbp1   retinal ganglion cells   Parkinson’s disease  

摘要： Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Mailer glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss, Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson's disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

关键词： Ischemic stroke   Early neurological deterioration   Clopidogrel   Genetic polymorphism   Platelet membrane receptor   Glycoprotein IIIa   Pharmacogenetics  

摘要： Background Early neurological deterioration (END) is common in acute ischemic stroke (IS). However, the underlying mechanisms for END are unclear. The aim of this study was to evaluate the associations of 16 variants in clopidogrel-relevant genes and interactions among these variants with END in acute IS patients receiving clopidogrel treatment. Methods We consecutively enrolled 375 acute IS patients between June 2014 and January 2015. Platelet aggregation was measured on admission and after the 7-10 days of clopidogrel treatment. The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry. The primary outcome was END within the 10 days of admission. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR) methods. Results Among the 375 patients, 95 (25.3%) patients developed END within the first 10 days of admission. Among the 16 variants, only CYP2C19*2 (rs4244285) AA/AG was associated with END using single-locus analytical approach. GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPIIIa rs2317676 on the risk for END. The high-risk interactions among the three variants were associated with the higher platelet aggregation and independent predictor for END after adjusting for the covariates (hazard ratio: 2.82;95% confidence interval: 1.36-7.76;P = 0.003). Conclusions END is very common in patients with acute IS. The mechanisms leading to END are most likely multifactorial. Interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPIIIa rs2317676 may confer a higher risk for END. It was very important to modify clopidogrel therapy for the patients carrying the high-risk interactive genotypes.

关键词： Tobacco smoke   Trauma   Brain injury   Oxidative stress   Blood-brain barrier   Tight junctions   Nrf2   Antioxidant  

摘要： Background Traumatic brain injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoke (TS) has been shown to promote vascular inflammation, neurovascular impairments, and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery. Methods Our study investigated the mechanisms underlying the exacerbation of TBI injury by TS using a weight drop model. For this purpose, male C57BL/6J mice, age range 6-8 weeks, were chronically exposed to premorbid TS for 3 weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. We analyzed the physical activity and body weight of the mice before TBI and 1 h, 24 h, and 72 h post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a critical antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including ZO-1, Occludin, and Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) and pro-inflammatory cytokines IL-6, IL-10, and TNF-alpha were assessed in blood samples. Results Our data revealed that premorbid TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS before TBI experienced a more significant weight loss, behavioral and motor activity deficiency, and slower post-TBI recovery when compared to TS-free TBI mice. Conclusion The effects of premorbid TS appear consequential to th

关键词： Chorioamnionitis   fetal brain   inflammation   neurodevelopmental outcome   prematurity  

摘要： Objective: Preterm premature rupture of membranes (PPROM) is a risk factor for chorioamnionitis (CA) and injury to the fetal brain. However, prolongation of gestation prevents morbidity and decreases complications of prematurity. The current investigation is to define risk factors for the adverse neurological outcome from the influence of PPROM of at least 7 days. Methods: A case-control study included three groups of preterm infants born at the University Hospitals Bonn and Essen, Germany. The first group consisted of infants with PPROM of at least 7 days and no chorioamnionitis (CA) (PPROM group), the second included preterm infants with CA (CA group), and the third group consisted of infants without PPROM and CA (control group). The outcome was assessed using Bayley Scales of Infant Development at a corrected age of 24 months. Each group consisted of 20 corresponding infants with an identical birth weight and gestational age at birth. Results: There was no significant difference between the mental development index (MDI) and psychomotor development index (PDI) scores (mean +/- SD): the MDI score was 101 +/- 14 in the PPROM group, 98 +/- 12 in the CA group and 96 +/- 17 in the control group;the PDI score 96 +/- 10, 89 +/- 16, and 90 +/- 17, respectively. Multiple regression analysis revealed no significant influence of PPROM and CA on neurological outcome. Conclusions: PPROM of at least 7 days has no influence on neurodevelopmental outcome at a corrected age of 24 months when birth is initiated in the case of beginning CA.

关键词： Oxaliplatin   Neuropathy   Hereditary   Risk factors   Charcot-Marie-tooth disease   Chemotherapy  

摘要： Oxaliplatin therapy can be complicated by chemotherapy-induced peripheral neuropathy (CIPN). Other neurotoxic chemotherapies have been linked to single nucleotide variants (SNV) in Charcot-Marie-Tooth disease (CMT) genes. Whether oxaliplatin carries increased risks of CIPN due to SNV in CMT-associated genes is unknown. 353 patients receiving oxaliplatin in NCCTG N08CB were serially evaluated for CIPN using a validated patient-reported outcome (PRO) instrument, the CIPN20 questionnaire (sensory scale). 49 canonical CMT-associated genes were analyzed for rare and common SNV by nextgen sequencing. The 157 patients with the highest and lowest susceptibility to CIPN (cases and controls) harbored 270 nonsynonymous SNV in CMT-associated genes (coding regions). 143 of these were rare, occurring only once ("singletons"). CIPN cases had 0.84 singletons per patient compared with 0.98 in controls. An imbalance in favor of cases was noted only in few genes including PRX, which was previously highlighted as a candidate CIPN gene in patients receiving paclitaxel. However, the imbalance was only modest (5 singleton SNV in cases and 2 in controls). Therefore, while singleton SNV were common, they did overall not portend an increased risk of CIPN. Furthermore, testing CMT-associated genes using recurrent non-synonymous SNV did not reveal any significant association with CIPN. Genetic analysis of patients from N08CB provides clinical guidance that oxaliplatin chemotherapy decisions should not be altered by the majority of SNV that may be encountered in CMT-associated genes when common genetic tests are performed, such as exome or genome sequencing. Oxaliplatin's CIPN risk appears unrelated to CMT-associated genes.

关键词： Attitudes   Care   End of life   Neurology   Reliability   Validity  

摘要： Background Knowing the opinions of patients with Progressive Neurological Diseases (PNDs) and their family members on end-of-life care can help initiate communication and the drawing up of a care plan. The aim of this paper is to describe the creation and psychometric properties of the newly developed APND-EoLC questionnaire (the Attitudes of Patients with Progressive Neurological Disease to End of Life Care questionnaire). Methods Following focus group discussion, four main areas of interest were identified: patients' and family members' attitudes towards end-of-life care, factors influencing decisions about treatment to prolong patients' life, concerns and fears regarding dying, and opinions on the system of care. The created questions were divided into domains based on factor analysis and psychometric properties were evaluated by sample of 209 patients with PND and 118 their family members. Results The final version of the scale contains a total of 28 questions divided into six domains (end-of-life control, keeping patients alive, trust in doctors/treatment, trust in social support, sense of suffering, and dependence/loss of control) and five individual questions determining views of the care system with specified response options. Construct validity was verified by confirmatory factor analysis for each evaluated area individually. Appropriate psychometric properties were identified in the questionnaire. Conclusions The APND-EoLC questionnaire can be recommended for use in both research and clinical practice.

关键词： Traumatic brain injury   Methamphetamine   Addiction   Interplay   Neurological outcomes  

摘要： Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in the world. TBI causes permanent physical, cognitive, social, and functional impairments. Substance use and intoxication are established risk factors for TBI. Data are emerging that also suggest that brain injury might be a risk factor for substance use. Methamphetamine (METH), a highly addictive psychostimulant, has not been thoroughly investigated in the context of TBI exposure. The interplay between the two has been of interest as their pathophysiology intertwines on many levels. However, the knowledge concerning the association between TBI-METH and the impact of chronic METH use on short and long-term TBI outcomes is equivocal at best. In this review of the literature, we postulate that, when combined, these two conditions synergize to result in more significant neuronal damage. As such, chronic exposure to METH before brain trauma may accentuate the pathophysiological signs of injury, worsening TBI outcomes. Similarly, individuals with a history of TBI would be more vulnerable to METH misuse and harmful effects. We, therefore, review the most recent preclinical and clinical data tackling the significant overlap in the pathophysiology of TBI and METH at three levels: the structural level, the biochemical level, and the cellular level. We also highlight some controversial results of studies investigating the outcomes of the interaction between TBI and METH.

关键词： Prostaglandin D2 synthase   Sleep disorders   Neurodegenerative diseases   Daytime sleepiness  

摘要： Background: Prostaglandin D2 (PGD2) induces sleep and may play a role in sleep and neurological disorders. We investigated PGD synthase (PGDS) levels in various sleep and neurological disorders. Methods: Sixty-three patients with neurological or sleep disorders (Parkinson's disease with excessive daytime sleepiness (PDS), n = 19;PD without sleepiness (PDWS), n = 14;Alzheimer's disease (AD), n = 10;narcolepsy (NA), n = 10;sleep apnea syndrome (SAS), n = 10) and 21 healthy controls were included in this study. Plasma lipocalin-type PGDS (L-PGDS) and glutathione-dependent hematopoietic PGDS (H-PGDS) levels were assessed using an enzyme-linked immunosorbent assay. Results: H-PGDS levels were not significantly different among the groups. Compared with healthy controls, the PDWS, PDS and AD groups had higher levels of L-PGDS. Neither H-PGDS nor L-PGDS levels correlated with scores on the Epworth Sleepiness Scale or Pittsburgh Sleep Quality Index in any group. Conclusion: We found higher levels of L-PGDS in patients with neurodegenerative diseases such as PD and AD. Whether increased L-PGDS levels reflect underlying sleepiness or the pathophysiology of neurodegenerative diseases needs further study.