Dynamics of quadrupedal locomotion of monkeys: implications for central control

We characterized the three-dimensional kinematics and dynamics of quadrupedal gait of young adult rhesus and cynomolgus monkeys while they walked with diagonal and lateral gaits at 0.4–1.0 m/s on a treadmill. Rigid bodies on the wrist, ankle, and back were monitored by an optical motion detection system (Optotrak). Kinematic data could be normalized using characteristic stride length, reducing variance due to different gait styles, to emphasize common characteristics of swing and stance parameters among animals. Mean swing phase durations fell as walking speed increased, but the swing phase durations increased at each walking velocity as a linear function of increases in amplitude, thereby following a main sequence relationship. The phase plane trajectories of the swing phases, i.e., plots of the relation of the rising and falling limb velocity to limb position in the sagittal (X–Z) plane, had unique dynamic characteristics. Trajectories were separable at each walking velocity and increases in swing amplitude were linearly related to peak swing velocities, thus comprising main sequences. We infer that the swing phase dynamics are set by central neural mechanisms at the onset of the swing phases according to the intended amplitude, which in turn is based on the walking velocity in the stance phases. From the many dynamic similarities between swing phases and rapid eye movements, we further suggest that the swing phases may be generated by neural mechanisms similar to those that produce saccades and quick phases of nystagmus from a signal related to sensed or desired walking velocity. Grants: This work was supported by National Institute of Health Grants EY11812, EY04148, DC05204, and EY01867.     

Determining a continuous marker for sleep depth

Detection and quantification of sleep arousals is an important issue, as the frequent arousals are known to reduce the quality of sleep and cause daytime sleepiness. In typical sleep staging, electroencephalograph (EEG) is the core signal and based on the visual inspection of the frequency content of EEG, non-rapid eye movement sleep is staged into four somewhat rough categories. In this study, we aimed at developing a continuous marker based on a more rigorous spectral analysis of EEG to measure or quantify the depth of sleep. In order to develop such a marker, we obtained the time-frequency map of two EEG channels around sleep arousals and identified the frequency bands that show the most change during arousals. We then evaluated classification performance of the potential signals for representing the depth of sleep, using receiver operating characteristic analysis. Our comparisons based on the area under the curve values revealed that the sum of absolute powers in alpha and beta bands is a good continuous marker to represent the depth of sleep. Higher values of this marker indicate low-quality sleep and vice versa. We believe that use of this marker will lead to a better quantification of sleep quality.     

A computer model for the clearance of insoluble particles from the tracheobronchial tree of the human lung

A multi-compartment model for the clearance of insoluble particles from the tracheobronchial tree of the human lung was created. As a significant innovation, the model considers specific mass transfer paths that may play an important role for slow bronchial clearance. These include the accumulation of particulate mass in the periciliary sol layer, an uptake of stored particles by airway macrophages, and the endocytosis of deposited mass by epithelial cells. Besides the gel layer representing fast mucociliary clearance, all cellular and extracellular units involved into the slow clearance process are described by respective compartments which are connected by specific transfer paths. The gastrointestinal tract (GIT), lymph nodes (LN), and blood capillaries are included into the model as final accumulation compartments, to which mass is transferred via the airway route and the transepithelial path. Besides a basic version of the model describing the whole tracheobronchial region by one set of compartments, also an advanced approach is introduced which, in accordance with the International Commission on Radiation Protection (ICRP), subdivides the conducting airways into a bronchial (BB) and bronchiolar (bb) part. Preliminary results were generated with MS-Excel from deposition data of 1-mummass median aerodynamic diameter (MMAD) particles, calculating local slow clearance fractions according to mathematical procedures introduced in previous publications. While mucociliary clearance is completely finished within 24h after exposure, slow clearance takes place in distinct phases and needs several days to weeks. This multi-stage event is also reflected in the respective retention curves which correspond well to previously published graphs.     

Perceived influence of intrinsic/extrinsic factors on participation in life activities after spinal cord injury

Background

Various types of limitations on community participation are experienced by people with spinal cord injury (SCI).

The Influence of In Vivo Metabolic Modifications on ADMET Properties of Green Tea Catechins–In Silico Analysis

The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B.     

英国药师职业发展体系介绍及启示

目的：调查英国药师职业发展体系、内容和特点,为完善我国执业药师职业发展体系提出建议。方法：通过文献研究和专家访谈的方式,收集近年来英国药师职业发展的各项资料,整理出英国药师管理部门、职业发展体系、教育培训内容和职业发展特点。并对照分析我国的药师职业发展情况。结果与结论：我国执业药师职业发展培训内容偏向理论,缺乏实用性;培训方式比较单一,对不同岗位、不同能力的执业药师没有针对性;执业药师职业发展认证机制不完善。应借鉴英国职业发展体系,从完善药师职业发展认证机制,促进职业发展多元化,尽早培养执业药师职业发展意识等方面来完善我国执业药师职业发展体系。     

基于pH梯度载药技术的咪喹莫特脂质体的制备工艺研究

目的 根据咪喹莫特的理化性质,利用pH梯度主动载药技术制备脂质体,考察其性状、粒径、表面电荷及体外释药特征。方法 葡聚糖凝胶滤过法测定脂质体的包封率,以包封率与成型性为主要指标筛选制备方法,考察水化液的种类、pH值、离子强度及pH梯度载药、磷脂-胆固醇比例、脂药比、维生素E用量对包封率的影响;正交试验优化咪喹莫特脂质体的处方,考察脂质体样品在0~4℃下的稳定性。结果 按处方咪喹莫特50 mg、大豆卵磷脂400 mg、胆固醇130 mg、油酸10 mg、维生素E 5 mg、柠檬酸pH 2.5缓冲液5 mL,采用薄膜分散法工艺制备脂质体样品,并进行pH梯度主动载药,pH值调至7.0。制得的咪喹莫特脂质体呈白色均匀的混悬液,脂质体微粒圆整,分散性好,粒径（347±21）nm,包封率（81.2±1.9）%,Zeta电位（-12.19±1.7）mV。结论 pH梯度主动载药技术适于咪喹莫特脂质体的制备。     

Buccal micronucleus cytome assay in primary school children: A descriptive analysis of the MAPEC_LIFE multicenter cohort study

Background

Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.

热休克转录因子-1表达与子宫内膜癌的临床特征及病理学关系

目的 探讨子宫内膜癌中热休克转录因子-1(HSF-1)蛋白的表达水平及其与患者临床病理学特征的关系.方法 选取2014年1月至2016年5月在周口市妇幼保健院收集的术后或活检经病理学证实为子宫内膜癌标本67例,既往收集的35例正常子宫内膜组织,采用免疫组化染色观察两组HSF-1蛋白的表达水平,并探讨其临床病理学意义.结果 子宫内膜癌组织标本中HSF-1蛋白阳性表达率71.64%(48/67),正常子宫内膜组织中HSF-1蛋白阳性表达率31.43%(11/35),两组阳性表达率比较差异有统计学意义(P<0.05);子宫内膜癌组织标本中HSF-1蛋白在高分化组织中阳性表达率86.96%高于中低分化组织的63.64%,浸润深度≤1/2肌层的阳性表达率87.50%高于≥1/2肌层的62.79%,淋巴结转移阴性组织中的阳性表达率为80.49%高于阳性组织的57.69%,均差异有统计学意义(P<0.05).结论 HSF-1蛋白在子宫内膜癌组织中表达水平显著升高,并且与肿瘤的组织分化程度、淋巴结转移及浸润深度有关.     

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.