Neural selectivity,efficiency, and dose equivalence in deep brain stimulation through pulse width tuning and segmented electrodes

BackgroundAchieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies.MethodsWe created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated.ResultsWe find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window.DiscussionWe find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.     

基于代谢组学探讨艾灸关元穴对老年大鼠肾能量代谢的影响＊

目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响，进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组（8只），21月龄SD雄性大鼠随机分为老年对照组（8只）、老年金匮肾气丸组（7只）、老年艾灸组（8只）。老年金匮肾气丸组每日按体重给药，老年艾灸组每日艾灸关元穴15 min，均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶（SDH）活性以及血清肾功能指标，观察肾脏病理变化，结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析，筛选代谢差异物并进行鉴定。结果 与老年对照组比较，老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高（P<0.01）。代谢组学结果显示，肾组织中筛选出13个共同差异化合物，分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC（16∶0/22∶5（7Z，10Z，13Z，16Z，19Z））、6，8-二羟基嘌呤、1，2，3-丙烷三羧酸、3-（4-甲氧基苯基）-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9，10-环氧十八烷酸、二十二碳五烯酸（22n-6）、牛磺胆酸、LysoPS （18∶0/0∶0）。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。     

消化道恶性肿瘤住院患者的能量消耗研究

目的评估消化道恶性肿瘤患者的能量消耗，探讨最佳计算公式及能量消耗的影响因素。方法采用连续入组法，纳入2016年3月至2016年12月在陆军军医大学第一附属医院肿瘤科住院治疗患者，运用代谢车测定其静息代谢能量（REE），使用Harris-Benedict公式和30kcal/（kg·d） 公式预测患者的一日总能量消耗（TEE）。收集研究对象的相关指标如年龄、身高、体重、病程、原位癌部位、是否荷瘤等。结果共纳入26例患者，其中包括食管癌11例，胃癌8例，结直肠癌7例，73%的患者处于高代谢状态，约69%的患者处于肿瘤Ⅳ期；其中不同病程和原位癌位置与静息能量消耗有差异，差异具有统计学意义；用30kcal/（kg·d）×体重估算TEE可能并不适用于消瘦的消化道肿瘤患者。结论消化道恶性肿瘤患者大多存在营养不良且处于高代谢状态，在给消化道恶性肿瘤患者提供能量时应适当考虑病程长短、肿瘤分期以及肿瘤部位等因素。尽量使用代谢车估算恶性肿瘤患者的TEE，若没有代谢车条件时，对于能下床活动的消化道恶性肿瘤患者，体质指数（BMI）≥18.5kg/m2者推荐使用30kcal/（kg·d）×实际体重的方法估算TEE，BMI<18.5kg/m2者推荐使用30kcal/（kg·d）×标准体重的方法估算TEE。     

Adverse events due to unnecessary radiation exposure in medical imaging reported in Finland

IntroductionAdverse events in radiology are quite rare, but they do occur. Radiation safety regulations and the law obligate organizations to report certain adverse events, harm and near misses, especially events related to patients' health and safety. The aim of this study was to describe and analyse incidents related to radiation safety issues reported in Finland.MethodsThe data were collected from incident reports documented by radiology personnel concerning notifications of abnormal events in medical imaging made to the Radiation and Nuclear Safety Authority between 2010 and 2017. During these eight years, 312 reports were submitted. Only events reported from radiology departments were included; nuclear medicine, radiotherapy and animal radiology cases were excluded. The final number of reports was 293 (94%).ResultsThe majority of the 293 approved reports were related to computed tomography (CT, 68.3%) and to X-ray examinations (27.6%). Altogether 82.9% of those irradiated were adults, most of whom were exposed to unnecessary radiation through CT (86.5%), 5.5% were children, and 4.4% pregnant women. The most common effective dose of unnecessary radiation was 1 mSv or less (89.7% of all examinations). The highest effective doses were reported in CT (from under 1 mSv–20 mSv and above). The reasons for the adverse events were incorrect identification (32%), incorrect procedure, site or side (30%); and human errors or errors of knowledge (20%).ConclusionAdverse events occurred especially in CT examinations. It is important to collect and analyse incident data, assess the harmful events, learn from them and aim to reduce adverse events.Implications for practiceThis study emphasizes the need for radiological personnel to obtain evidence-based information on adverse events and focus on training to improve patient safety.     

吗啡依赖和戒断对大鼠杏仁核神经甾体和氨基酸递质水平的影响

目的研究吗啡依赖和戒断时大鼠杏仁核中神经甾体和氨基酸递质水平的变化。方法连续7天给予大鼠盐酸吗啡建立吗啡依赖模型。使用纳洛酮(2mg/kg)催促戒断,观察戒断症状并进行评分。将大鼠断头处死后,剥离大脑并分离出杏仁核,用液-液萃取和固相萃取法提取游离型和结合型神经甾体。神经甾体(包括脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯和孕烯醇酮硫酸酯)的含量使用高效液相色谱-质谱法测定。甘氨酸、谷氨酸和γ-氨基丁酸的含量采用柱前OPA衍生-电化学检测-高效液相色谱法测定。结果与盐水对照组相比,吗啡依赖大鼠杏仁核中的脱氢表雄酮水平降低33 %(P<0·01)。与戒断对照组比较,吗啡戒断大鼠杏仁核中的孕烯醇酮和别孕烯醇酮水平分别升高45 %和42 %(P<0·05) ,γ-氨基丁酸水平降低18 %(P<0·01)。与吗啡依赖组比较,吗啡戒断组大鼠杏仁核中的孕烯醇酮和孕烯醇酮硫酸酯水平分别升高60 %和40 %(P<0·05) ,甘氨酸水平降低14 %(P<0·05)。结论吗啡依赖大鼠杏仁核中的脱氢表雄酮可能参与吗啡依赖的形成而与吗啡戒断症状的表达无关。其他神经甾体(包括孕烯醇酮、别孕烯醇酮和孕烯醇酮硫酸酯)则可能参与吗啡的戒断而与依赖的形成无关。纳洛酮催促戒断时,大鼠杏仁核中抑制性氨基酸递质的合成和释放受到抑制。表明大鼠杏仁核中的各种神经甾体和氨基酸递质在吗啡依赖和戒断时发生了不同的变化。     

Physical laws of cholesterol gallstone fragmentation

Efficient fragmentation is the most important prerequisite for successful treatment of gallstones by extracorporeally induced shock waves. No data are available on the amount of energy necessary for stone disintegration and on the threshold energy below which no further fragmentation occurs. We therefore performed an in vitro investigation on human cholesterol gallstones to elucidate physical laws governing shock-wave lithotripsy. First, the focal pressure of the lithotripter was measured to calculate the energy traversing a stone. Second, 96 gallstones from 16 gall bladders were analysed with respect to physicochemical composition, radiological features and ultrasound before fragmentation was performed. Energy for stone disintegration was constant within each stone family but varied between 4.6 J mL^?1 and 36.8 J mL^?1 in different families. This energy correlated linearly with stone volume. None of the radiological and physicochemical factors revealed a clear-cut correlation of the different energies necessary for similar stone disintegration. The threshold energy differed between 0.26 mJ and 1.04 mJ per pulse. In conclusion, stone volume was the best parameter predicting stone fragmentation. However, in cholesterol stones with a similar composition the required energy per volume varies considerably together with the threshold energy. Radiological and ultrasound parameters appear to be of minor importance in explaining these differences.     

小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

Personality traits of agreeableness and extraversion are associated with ADH4 variation.

BACKGROUND: Personality traits are associated with substance dependence (SD); genetic factors may influence both. Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study. METHODS: We assessed dimensions of the five-factor model of personality in 243 subjects with SD (175 European Americans [EAs] and 68 African Americans [AAs]) and 296 healthy control subjects (256 EAs and 40 AAs). We also genotyped 7 ADH4 markers (spanning the locus) and 38 unlinked ancestry-informative markers in these subjects. The relationships between the diplotypes, alleles, and genotypes at ADH4 and personality traits were examined using multivariate analysis of covariance (MANCOVA), controlling for potential confounders. RESULTS: Generally, SD patients, older individuals, and male subjects scored higher on neuroticism and lower on other personality factors. Personality factors were associated with the diplotypes. The allele A or genotype A/A of single nucleotide polymorphism (SNP)6 (rs1800759 at the gene promoter) was significantly associated with agreeableness scores. There were associations between extraversion and SNP1 (hcv2033010 at the 3' end) and SNP2 (rs1042364 in exon 9) in subjects with higher conscientiousness scores. CONCLUSIONS: The personality traits of agreeableness and extraversion are related to ADH4 polymorphism. Among the ADH4 markers that appear to predispose to certain personality traits, the functional variant rs1800759 (SNP6) in the promoter region is most important. We conclude that personality traits and SD have a partially overlapping genetic basis.