内镜柔性器械腱鞘传动模型及实验研究

目的 建立内镜柔性器械腱鞘系统的推力传动模型，研究影响传动效率的关键因素。方法 建立腱鞘系统在器械推送作用下力和位移的传动模型并进行仿真计算；搭建腱鞘系统传动测试的实验平台以验证模型的准确性，研究传动速度、腱鞘直径比、弯曲半径等对传动效率的影响。结果 腱鞘传动过程中存在显著的非线性传递现象，传动模型仿真与实验结果基本符合；传动速度、腱鞘直径比、弯曲半径均对内镜柔性器械的推力传动有较大影响，对位移传动的影响相对小一些。结论 该模型可用于内镜柔性器械中腱鞘系统推力传动的计算，提供给医生器械工作末端的力反馈，以保证器械的安全操作和提高手术效果；在内镜柔性器械的精准控制中需要综合考虑传动速度、腱鞘传动比、弯曲半径等对运动传递的影响。     

Improving IMDC Prognostic Prediction Through Evaluation of Initial Site of Metastasis in Patients With Metastatic Renal Cell Carcinoma

BackgroundSeveral models are adopted in clinical practice to estimate prognosis of patients with metastatic renal cell carcinoma (mRCC); however, none of these models have evaluated patients treated by immune-checkpoint inhibitors. The aim of this study was to investigate if the site of initial metastasis could be a parameter able to stratified prognosis among patients with mRCC among different risk groups defined by the International Metastatic Renal Cell Database Consortium (IMDC) model. The site of initial metastasis was defined as the primary tissue or organ in which metastasis was diagnosed in the course of the medical history of the disease.Patients and MethodsA total of 134 patients treated between January 2010 and December 2018 in our institution were retrospectively evaluated. The primary outcome was overall survival (OS) defined as the time from initiation of first-line therapy to death from any cause. Of note, 26 (19.4%) patients received immune-checkpoint inhibitors. Univariable analysis was performed through the log-rank test to estimate the effect of number of metastatic sites and site of initial metastasis on OS. Subsequently, a Cox regression proportional hazards model was employed in multivariable analysis.ResultsOf the 12 variables analyzed, 4 were statistically associated to worse OS in univariable analysis (number of metastases and liver, bone, or central nervous system metastases). Multivariate analysis confirmed that bone (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.17-3.13), liver (HR, 2.65; 95% CI, 1.59-4.42), and central nervous system (HR, 3.3; 95% CI, 1.62-6.74) initial metastases were independent parameters related to worse OS. The presence of 1 or more of the selected sites recognized specific populations of patients associated to worse prognosis in both good (P = .003) and intermediate (P = .047) risk groups.ConclusionThe site of initial metastasis defines specific populations of patients associated with worse prognosis in the good and intermediate IMDC groups.     

A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer‐reviewed publications. However, no human‐ or machine‐readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state‐of‐the‐art information technology, we have developed a cloud‐based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 90 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects the differences and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified potential connections, that is, specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org , an open‐access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible potential connections. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org . Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This data set allows for large‐scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open‐source at Hippocampome.org in order to further research across disciplines.     

Characterization of a Parkinson’s disease rat model using an upgraded paraquat exposure paradigm

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.     

Cognitive behavioral therapy reduces illness perceptions and anxiety symptoms in patients with unruptured intracranial aneurysm

The main purpose of this study was to assess the relation between cognitive behavioral therapy and possible changes in illness perceptions and anxiety in patients diagnosed with unruptured intracranial aneurysm. An observational study of an intervention with 67 patients with an unruptured intracranial aneurysm from two medical centers in a Colombian city (n = 35 on the intervention group) was carried out. To assess changes, measurements were taken at baseline and at one-year follow-up with the Beck Anxiety Inventory and the Illness Perception Questionnaire, brief version, taking into account the importance of perceptions in the process of adjusting to illness and acquiring healthy life habits. Hypotheses were tested by a structural model. The results obtained from this study showed that illness perceptions were related to anxiety levels at both time points; however, the relations were stronger before cognitive behavioral therapy (βt0 = 0.61, p < 0.01; βt1 = 0.37, p < 0.01). Cognitive behavioral therapy was found to be a moderator of changes in both illness perceptions and anxiety at the time of follow-up (β = −0.31, p < 0.01; β = −0.26, p < 0.01). The structural model suggests that cognitive behavioral therapy is associated with less anxiety (β = −0.17, p < 0.05) and better illness perceptions (β = −0.35, p < 0.01) in patients diagnosed with unruptured intracranial aneurysms.     

Dyskinesia Matters

Levodopa-induced dyskinesia (LID) represents a significant source of discomfort for people with Parkinson's disease (PD). It negatively affects quality of life, it is associated with both motor and nonmotor fluctuations, and it brings an increased risk of disability, balance problems, and falls. Although the prevalence of severe LID appears to be lower than in previous eras (likely owing to a more conservative use of oral levodopa), we have not yet found a way to prevent the development of this complication. Advanced surgical therapies, such as deep brain stimulation, ameliorate LID, but only a minority of PD patients qualify for these interventions. Although some have argued that PD patients would rather be ON with dyskinesia than OFF, the deeper truth is that patients would very much prefer to be ON without dyskinesia. As researchers and clinicians, we should aspire to make that goal a reality. To this end, translational research on LID is to be encouraged and persistently pursued. © 2019 International Parkinson and Movement Disorder Society     

Decision-support models for empiric antibiotic selection in Gram-negative bloodstream infections

Objectives

Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia.