Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society     

Judging roughness by sight—A 7‐tesla fMRI study on responsivity of the primary somatosensory cortex during observed touch of self and others

Observing another person being touched activates our own somatosensory system. Whether the primary somatosensory cortex (S1) is also activated during the observation of passive touch, and which subregions of S1 are responsible for self‐ and other‐related observed touch is currently unclear. In our study, we first aimed to clarify whether observing passive touch without any action component can robustly increase activity in S1. Secondly, we investigated whether S1 activity only increases when touch of others is observed, or also when touch of one's own body is observed. We were particularly interested in which subregions of S1 are responsible for either process. We used functional magnetic resonance imaging at 7 Tesla to measure S1 activity changes when participants observed videos of their own or another's hand in either egocentric or allocentric perspective being touched by different pieces of sandpaper. Participants were required to judge the roughness of the different sandpaper surfaces. Our results clearly show that S1 activity does increase in response to observing passive touch, and that activity changes are localized in posterior but not in anterior parts of S1. Importantly, activity increases in S1 were particularly related to observing another person being touched. Self‐related observed touch, in contrast, caused no significant activity changes within S1. We therefore assume that posterior but not anterior S1 is part of a system for sharing tactile experiences with others. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

血清钙结合蛋白S100A12对肺炎支原体肺炎患儿严重程度的预测价值#br#

目的　探讨血清钙结合蛋白S100A12预测肺炎支原体肺炎（MPP）患儿严重程度的临床意义。方法　选取2018年1月—2019年6月南昌市第三医院儿科收治的100例MPP患儿,根据病情严重程度分为MPP组60例和重症MPP（SMPP）组40例,另选取同期在我院体检健康儿童20例作为对照组。采集血清标本后检测白细胞计数（WBC）、中性粒细胞比例（N）、淋巴细胞比例（L）、C反应蛋白（CRP）水平,采用酶联免疫吸附法检测血清钙结合蛋白S100A12水平。分别比较MPP组和SMPP组急性期及恢复期S100A12的差异,分析S100A12与MPP患儿严重程度的相关性,受试者工作特征（ROC）曲线分析S100A12对重症MPP的预测价值。结果　与对照组比较,MPP组和SMPP组急性期患儿血清S100A12水平显著升高（P＜0.01）;且SMPP组急性期血清S100A12水平较MPP组显著升高（P＜0.05）;MPP组和SMPP组恢复期和对照组血清S100A12水平差异无统计学意义（P＞0.05）。相关性分析结果显示,S100A12与MPP患儿严重程度呈正相关（rs=0.824,P＜0.01）。ROC曲线分析结果显示S100A12预测SMPP的曲线下面积分别为0.916（95%CI：0.843~0.962）,最佳临界值为827.64 μg/L,此时敏感度为95.00%,特异度为83.33%。结论　血清S100A12水平升高可预测儿童MPP的严重程度。     

艾司洛尔联合右美托咪定对重型颅脑创伤患者去骨瓣 减压术后脑代谢及预后的影响

目的　探讨艾司洛尔联合右美托咪定对重型颅脑创伤去骨瓣减压术患者脑脊液（CSF）中乳酸、S100B表达,颅内压（ICP）以及预后的影响。方法　选取2015年1月—2018年12月行单侧去骨瓣减压的重型颅脑创伤患者60例为观察对象,采用随机信封法分为艾司洛尔联合右美托咪定治疗组（联合治疗组,30例）与单用右美托咪定治疗组（对照组,30例）。记录治疗前和治疗后1、3、7 d颅内压变化及CSF中乳酸和S100B蛋白水平,比较2组患者治疗后14 d格拉斯哥昏迷（GCS）评分和美国国立卫生研究院卒中量表（NIHSS）评分及不良反应发生情况。出院后共随访6个月,采用Glasgow预后分级（GOS）评价2组患者的预后。结果　联合治疗组患者治疗后1、3、7 d其CSF乳酸含量、S100B水平和ICP均低于对照组（P＜0.05）;联合治疗组治疗后14 d GCS评分及NIHSS评分高于对照组（P＜0.01）;出院后6个月随访时2组患者GOS评分差异无统计学意义（P＞0.05）。结论　艾司洛尔联合右美托咪定联合治疗可降低重型颅脑创伤去骨瓣术患者CSF乳酸水平和S100B蛋白表达,改善患者的短期预后,但并未改善长期预后。     

Use of human liver and EpiSkin™ S9 subcellular fractions as a screening assays to compare the in vitro hepatic and dermal metabolism of 47 cosmetics-relevant chemicals

The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients.     

MicroRNA-147b suppresses the proliferation and invasion of non-small-cell lung cancer cells through downregulation of Wnt/β-catenin signalling via targeting of RPS15A

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/β-catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/β-catenin signalling and suggest that the miR-147b/RPS15A/Wnt/β-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.     

Natural Language Processing of Radiology Reports in Patients With Hepatocellular Carcinoma to Predict Radiology Resource Utilization

ObjectiveRadiology is a finite health care resource in high demand at most health centers. However, anticipating fluctuations in demand is a challenge because of the inherent uncertainty in disease prognosis. The aim of this study was to explore the potential of natural language processing (NLP) to predict downstream radiology resource utilization in patients undergoing surveillance for hepatocellular carcinoma (HCC).Materials and MethodsAll HCC surveillance CT examinations performed at our institution from January 1, 2010, to October 31, 2017 were selected from our departmental radiology information system. We used open source NLP and machine learning software to parse radiology report text into bag-of-words and term frequency–inverse document frequency (TF-IDF) representations. Three machine learning models—logistic regression, support vector machine (SVM), and random forest—were used to predict future utilization of radiology department resources. A test data set was used to calculate accuracy, sensitivity, and specificity in addition to the area under the curve (AUC).ResultsAs a group, the bag-of-word models were slightly inferior to the TF-IDF feature extraction approach. The TF-IDF + SVM model outperformed all other models with an accuracy of 92%, a sensitivity of 83%, and a specificity of 96%, with an AUC of 0.971.ConclusionsNLP-based models can accurately predict downstream radiology resource utilization from narrative HCC surveillance reports and has potential for translation to health care management where it may improve decision making, reduce costs, and broaden access to care.     

Dosimetric and radiobiological investigation of permanent implant prostate brachytherapy based on Monte Carlo calculations

PurposePermanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose calculations via retrospective dosimetric and radiobiological analysis for a new patient cohort.Methods and MaterialsA cohort of 155 patients treated with permanent implant prostate brachytherapy from The Ottawa Hospital Cancer Centre is considered. Monte Carlo (MC) dose calculations are performed using tissue-based virtual patient models. Dose–volume histogram (DVH) metrics (target, organs at risk) are extracted from 3D dose distributions and compared with those from calculations under TG-43 assumptions (TG43). Equivalent uniform biologically effective dose and tumor control probability are calculated.ResultsFor the target, D₉₀ (V₁₀₀) is 136.7 ± 20.6 Gy (85.8% ± 7.8%) for TG43 and 132.8 ± 20.1 Gy (84.1% ± 8.2%) for MC; D₉₀ is 3.0% ± 1.1% lower for MC than TG43. For organs at risk, MC D_1cc = 104.4 ± 27.4 Gy (TG43: 106.3 ± 28.3 Gy) for rectum and 80.8 ± 29.7 Gy (TG43: 78.4 ± 28.4 Gy) for bladder; D_1cc = 185.9 ± 30.2 Gy (TG43: 191.1 ± 32.0 Gy) for urethra. Equivalent uniform biologically effective dose and tumor control probability are generally lower when evaluated using MC doses. The largest dosimetric and radiobiological discrepancies between TG43 and MC are for patients with intraprostatic calcifications, for whom there are low doses (cold spots) in the vicinity of calcifications within the target, identified with MC but not TG43.ConclusionsDVH metrics and radiobiological indices evaluated with TG43 are systematically inaccurate by upward of several percent compared with MC patient-specific models. Mean cohort DVH metrics and their MC:TG43 variances are sensitive to patient cohort and clinical practice, underlining the importance of further retrospective MC studies toward widespread clinical adoption of advanced model-based dose calculations.