Two types of ictal phase-amplitude couplings in epilepsy patients revealed by spectral harmonicity of intracerebral EEG recordings

ObjectiveSpectral harmonicity of the ictal activity was analyzed regarding two clinically relevant aspects, (1) as a confounding factor producing ‘spurious’ phase-amplitude couplings (PAC) which may lead to wrong conclusions about the underlying ictal mechanisms, and (2) its role in how good PAC is in correspondence to the seizure onset zone (SOZ) classification performed by the epileptologists.MethodsPAC patterns observed in intracerebral electroencephalography (iEEG) recordings were retrospectively studied during seizures of seven patients with pharmacoresistant focal epilepsy. The time locked index (TLI) measure was introduced to quantify the degree of harmonicity between frequency bands associated to the emergence of PAC during epileptic seizures.Results(1) Harmonic and non harmonic PAC patterns coexist during the seizure dynamics in iEEG recordings with macroelectrodes. (2) Harmonic PAC patterns are an emergent property of the periodic non sinusoidal waveform constituting the epileptiform activity. (3) The TLI metric allows to distinguish the non harmonic PAC pattern, which has been previously associated with the ictal core through the paroxysmal depolarizing shifts mechanism of seizure propagation.ConclusionsOur results suggest that the spectral harmonicity of the ictal activity plays a relevant role in the visual analysis of the iEEG recordings performed by the epileptologists to define the SOZ, and that it should be considered for the proper interpretation of ictal mechanisms.SignificanceThe proposed harmonicity analysis can be used to improve the delineation of the SOZ by reliably identifying non harmonic PAC patterns emerging from fully recruited cortical and subcortical areas.     

In vitro myogenesis induced by human recombinant elastin-like proteins

Mammalian adult skeletal muscle has a limited ability to regenerate after injury, usage or trauma. A promising strategy for successful regenerative technology is the engineering of bio interfaces that mimic the characteristics of the extracellular matrix. Human elastin-like polypeptides (HELPs) have been synthesized as biomimetic materials that maintain some peculiar properties of the native protein. We developed a novel Human Elastin Like Polypeptide obtained by fusing the elastin-like backbone to a domain present in the α2 chain of type IV collagen, containing two RGD motives. We employed this peptide as adhesion substrate for C2C12 myoblasts and compared its effects to those induced by two other polypeptides of the HELP series. Myoblast adhered to all HELPs coatings, where they assumed morphology and cytoarchitecture that depended on the polypeptide structure. Adhesion to HELPs stimulated at a different extent cell proliferation and differentiation, the expression of Myosin Heavy Chain and the fusion of aligned fibers into multinucleated myotubes. Adhesion substrates significantly altered myotubes stiffness, measured by Atomic Force Microscopy, and differently affected the cells Ca²⁺ handling capacity and the maturation of excitation-contraction coupling machinery, evaluated by Ca²⁺ imaging. Overall, our findings indicate that the properties of HELP biopolymers can be exploited for dissecting the molecular connections underlying myogenic differentiation and for designing novel substrates for skeletal muscle regeneration.     

Positive association between cerebral grey matter metabolism and dopamine D2/D3 receptor availability in healthy and schizophrenia subjects: An 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography study

Abstract

Objectives: Overlapping decreases in extrastriatal dopamine D₂/D₃-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.

Methods: To ascertain this, we used two consecutive ¹⁸F-fluorodeoxyglucose and ¹⁸F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.

Results: ¹⁸F-fluorodeoxyglucose uptake and ¹⁸F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D₂/D₃-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.

Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.     

Repurposing fallen leaves to bio-based reaction medium for hydration,hydroxylation, carbon-carbon and carbon-nitrogen bond formation reactions

A green reaction medium has been developed from the Water Extract of Teak leaf (Tectona grandis) ash (WET). The alkaline nature of the WET was successfully applied towards hydration of nitriles, conversion of arylboronic acids to phenols with 30% aqueous H₂O₂, Knoevenagel condensation for benzylidenemalononitrile derivatives formation and Chan-Lam reaction of arylboronic acids with imidazole derivatives. In current protocols dual role of WET as reaction medium as well as base has been explored. A wide range of substrates with varying electronic natures is compatible under these WET mediated reaction conditions with excellent yields.     

浅析医学科普进中学对临床医学生能力的培养

扎实的医学基础知识和临床技能是医学生向医生身份成功转变的前提。素质教育改革非常注重学生“全面有个性发展”。教师在教学中除要引导医学生培养正确学习习惯以外,还要积极的促进统筹规划、人际沟通、心理素质的提升,培养出良好的综合思维,这也是当今医学教育中较为薄弱和有待创新的工作。医学教育离不开教学与实践,实现二者的良好耦合,才能达到“以学促践,以践辅学”的效果。笔者以“教中学”模式入手,以中南大学湘雅三医院医学科普实践为例,着重分析了医学科普走进中学生的教学实践活动。探讨此种实践活动对医学生在思维能力、临床操作技能、医患沟通能力、论文写作能力等方面的作用。     

中药产业供应链绿色生产力测算框架及实证研究＊

目的 中药行业开展绿色供应链管理已经成为应对资源与环境压力、获得国际竞争力的重要战略，研究中药产业供应链绿色生产力的测算框架具有重要的现实意义。方法 本研究基于对绿色价值流图构建分析框架上，分析中药供应链中的各链条组成部分，以识别“浪费”的来源，从而设计供应链经济指标和环境指标。结果 计算供应链的经济指数和环境指数，创新供应链绿色生产力量化测算框架，运用民营企业数据实证其可行性。结论 绿色生产力指数测算框架为企业制定供应链规划方案，提高供应链绿色生产力水平提供了有效的测量手段。     

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation

BackgroundObsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized.Objective/hypothesisThe primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc).MethodsWe compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 μs). In addition, intracranial EEG was recorded directly from depth macroelectrodes in the NAc in four OCD patients.ResultsCross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16–25 Hz) -gamma (110–166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported.ConclusionWe reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches.