A mathematical model that predicts the force-frequency relationship of human skeletal muscle

In previous work we developed and validated a mathematical model that predicted force output from skeletal muscles subjected to six-pulse stimulation trains under isometric condition. The current study investigated the model's ability to predict force responses to longer stimulation trains under both nonfatigued and fatigued conditions. Using the six-pulse train model to predict the force produced by longer stimulation trains showed that the model was successful, but a modified parameter identification scheme was required. For most of the trains tested the model accounted for 95% of the variance in the experimental forces produced by stimulation trains, with mean frequencies from 12.5 to 100 HZ, train durations from 485 to 1000 ms, and number of pulses from 14 to 50 for both nonfatigued and fatigued muscles. The success of our mathematical model in predicting forces produced by stimulations with a wide range of frequencies, durations, and number of pulses implies great potential of the model for the identification of optimal activation patterns that should be used during functional electrical stimulation.     

A new method for monitoring abnormal muscle response in hemifacial spasm: A prospective study

Objective

To examine a new abnormal muscle response (AMR) monitoring method during microvascular decompression (MVD) for hemifacial spasm.

A new method for measuring compound muscle action potentials in facial palsy: a preliminary study

To establish a simple, reproducible procedure for studying facial motor nerve conduction (MNC), we determined the optimal electrode position to record evoked compound muscle action potentials (CMAPs) from perioral muscles in normal subjects. We examined three new electrode positions in which the electrode connected to the one input of the amplifier was placed on the mental protuberance, and the one connected to the other input was placed on the skin over the orbicularis oris muscle (the philtrum, mouth angle, or lower lip). We then compared the morphology and amplitudes of the CMAPs, right-left differences, and the reproducibility of CMAP amplitudes with recordings taken from the standard electrode position in which one electrode was placed on the nasolabial fold closely lateral to the ala nasi, and the other was placed on the skin over the orbicularis oris. Percutaneous supramaximal electrical stimulation was applied to the main trunk of the facial nerve. All three of the new recording positions showed greater amplitudes and more obvious biphasic CMAPs than the standard method. Positioning the electrode connected to the negative input on the philtrum was optimal in terms of right-left differences and the reproducibility of CMAP amplitudes. Therefore, this midline recording is a simple, reproducible method for calculating the CMAP amplitude ratio. However, prior to clinical use of this procedure, analyses of patients with facial palsy are required.     

一种改良大鼠四血管阻塞法脑缺血模型

目的建立一种稳定可靠的可降低侧支循环影响的大鼠全脑缺血模型操作方法。方法实验用SD大鼠50只随机分为3组：假手术组；缺血15min组；缺血25min组，在麻醉状态下仰卧固定，打开胸廓上口，分离并夹闭双侧锁骨下动脉起始段；后两组动物待接近清醒时分别夹闭其双侧颈总动脉15min和25min后松开动脉夹实行再灌注。各组动物分别于手术后24h、48h、72h和7d进行神经功能测试，并于最后一次测试后立即灌注固定组织，取脑组织进行组织学观察，统计海马、皮层等区域神经细胞的状态进行比较，以海马CA1区大部分神经元细胞出现死亡为模型成功标准。结果与假手术组相比，15min组和25min组之存活动物均显示出明显的神经功能降低，其组织学观察结果亦非常稳定，剔除因抽搐死亡的动物后模型成功率可达到100％（试验中未观察到存活动物模型失败的情况）。其中，25min组的动物死亡率高于15min组，并可观察到较15min组更加广泛的神经元坏死。结论本改良四血管阻塞法大鼠全脑缺血模型可明显提高模型制作的可靠性和成功率。     

A method for ordinal outcomes: The ordered stereotype model

Objective : The collection and use of ordinal variables are common in many psychological and psychiatric studies. Although the models for continuous variables have similarities to those for ordinal variables, there are advantages when a model developed for modeling ordinal data is used such as avoiding “floor” and “ceiling” effects and avoiding to assign scores, as it happens in continuous models, which can produce results sensitive to the score assigned. This paper introduces and focuses on the application of the ordered stereotype model, which was developed for modeling ordinal outcomes and is not so popular as other models such as linear regression and proportional odds models. This paper aims to compare the performance of the ordered stereotype model with other more commonly used models among researchers and practitioners. Methods : This article compares the performance of the stereotype model against the proportional odd and linear regression models, with three, four, and five levels of ordinal categories and sample sizes 100, 500, and 1000. This paper also discusses the problem of treating ordinal responses as continuous using a simulation study. The trend odds model is also presented in the application. Results : Three types of models were fitted in one real‐life example, including ordered stereotype, proportional odds, and trend odds models. They reached similar conclusions in terms of the significance of covariates. The simulation study evaluated the performance of the ordered stereotype model under four cases. The performance varies depending on the scenarios. Conclusions : The method presented can be applied to several areas of psychiatry dealing with ordinal outcomes. One of the main advantages of this model is that it breaks with the assumption of levels of the ordinal response are equally spaced, which might be not true.     

A new method for receptor autoradiography: [H]Opioid receptors in rat brain

Opioid receptors can be labeled with [³H]ligands in lightly fixed tissue sections mounted on microscope slides. The preparation of these sections does not seem to alter any of the known characteristics of opioid receptors. The light microscopic autoradiographic distribution of these binding sites can be observed if one attaches emulsion-coated coverslips to these slides to obtain autoradiograms. The distribution of [³H]diprenorphine binding sites determined by this in vitro method is identical to the distribution found in earlier studies utilizing in vivo labeling of opioid receptors. In addition, [³H]opioid peptide binding sites and [³H]dihydromorphine binding sites may be similar, perhaps identical, to those for [³H]diprenorphine, an opiate antagonist.

This method has several important advantages over earlier methods for determining the autoradiographic localization of receptors. It is possible, by washing, to reduce nonspecific binding to low levels. Since receptor labeling is performed with single tissue sections mounted on slides, one can examine different receptors in different but adjacent sections. One can use ligands that are not entirely suitable for in vivo labeling (For example, one can use [³H]peptides which do not normally cross the blood-brain barrier). One can perform autoradiographic studies after laveling tissues under a wide variety of conditions (For example, one can examine the effects of various ions and nucleotides on ligand binding distributions). This technique seems to be free of various artifacts, such as edge artifacts, which were common by techniques used in our laboratory earlier. Since one does not have to load an entire animal with radioactive ligand as one must with in vivo labeling, this approach is economically advantageous. One can use postmortem tissue, including that from humans to study receptor distribution with a high anatomical resolution.     

Syrian hamster infected with Leishmania infantum: A new experimental model for inflammatory myopathies

Idiopathic inflammatory myopathies (IIMs) are inflammatory disorders of unknown origin. On the basis of clinical, histopathological, and immunological features, they can be differentiated into three major and distinct subsets: dermatomyositis; polymyositis; and inclusion‐body myositis. Although a few animal models for IIM are currently available, they lack several characteristic aspects of IIMs. The aim of our study was to examine skeletal muscle involvement in an experimental animal model of visceral leishmaniasis, a disseminated infection caused by the protozoan parasite Leishmania infantum, and to compare features of associated inflammation with those of human IIM. Syrian hamsters infected intraperitoneally with amastigotes of L. infantum were killed at 3 or 4 months post‐infection, and the skeletal muscles were studied. Focal inflammation was predominantly observed in the endomysium and, to a lesser extent, in perivascular areas. Degenerating muscle fibers were also found, as well as myonecrosis. Immunofluorescence with confocal laser scanning microscopy was used to characterize the phenotype of inflammatory infiltrates and the distribution of MHC class I and II in muscle biopsies. The infiltrating inflammatory cells consisted mainly of T cells, and CD8⁺ T cells were found in non‐necrotic muscle fibers that expressed MHC class I on the sarcolemma. In addition to T cells, several macrophages were present. The model we are proposing closely resembles polymyositis and may be useful in studying certain aspects of this disease such as the role of T cells in muscle inflammation and myocytotoxicity, while also providing novel therapeutic targets. Muscle Nerve, 2009     

Characterization of intercostal muscle pathology in canine degenerative myelopathy: A disease model for amyotrophic lateral sclerosis

Dogs homozygous for missense mutations in the SOD1 gene develop a late‐onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end‐stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease‐related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. © 2013 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.     

A computationally efficient method for accurately solving the EEG forward problem in a finely discretized head model.

OBJECTIVE: Solution of the forward problem using realistic head models is necessary for accurate EEG source analysis. Realistic models are usually derived from volumetric magnetic resonance images that provide a voxel resolution of about 1 mm3. Electrical models could, therefore contain, for a normal adult head, over 4 million elements. Solution of the forward problem using models of this magnitude has so far been impractical due to issues of computation time and memory. METHODS: A preconditioner is proposed for the conjugate-gradient method that enables the forward problem to be solved using head models of this magnitude. It is applied to the system matrix constructed from the head anatomy using finite differences. The preconditioner is not computed explicitly and so is very efficient in terms of memory utilization. RESULTS: Using a spherical head model discretized into over 4 million volumes, we have been able to obtain accurate forward solutions in about 60 min on a 1 GHz Pentium III. L2 accuracy of the solutions was better than 2%. CONCLUSIONS: Accurate solution of the forward problem in EEG in a finely discretized head model is practical in terms of computation time and memory. SIGNIFICANCE: The results represent an important step in head modeling for EEG source analysis.     

A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis

Systemic sclerosis is a connective tissue disease that involves the gastrointestinal (GI) tract. Seventy-five per cent of systemic sclerosis patients experience symptoms arising from oesophagus. The intestine has less frequently been subject for studies than the oesophagus. When the small intestine becomes involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur. Previous studies have shown decreased and abnormal intestinal motility, dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic sclerosis patients using novel analysis of intestinal muscle contraction force-velocity and power. A volume-controlled duodenal ramp-distension protocol was used in nine patients and eight healthy controls. The wall stretch ratio, tension, shortening velocity and muscle power were computed from pressure and cross-sectional area data recorded by an impedance planimetry system. The tension-stretch ratio relation obtained in patients was shifted to the left, indicating a stiffer wall. The in vivo tension-shortening velocity relationship was quantified using Hill's equation. The maximum preload tension (tension at zero velocity) was lower in the patients than in the healthy controls (P < 0.001). The muscle power was lowest in the patients. An association was found between the duration of the disease and the maximum stretch ratio (P < 0.05). The study represents the first data with application of in vivo muscle force-velocity relations in patients with gastrointestinal diseases. Systemic sclerosis patients had increased stiffness and impaired muscle dynamics of the duodenum. Decreased muscle function and increased wall stiffness may explain the GI symptoms reported in this patient group.     

A new method for analysing transition to psychosis: Joint modelling of time‐to‐event outcome with time‐dependent predictors

An active area in psychosis research is the identification of predictors of transition to a psychotic state among those who are assessed as being at high risk of psychosis. Many of the potential predictors are time dependent in the sense that they may change over time and are measured at a number of assessment time points. Examples are various psychopathological measures such as negative symptoms, positive symptoms, depression, and anxiety. Most research in transition to psychosis has not made use of the dynamic nature of these measures, probably because suitable statistical methods and software have not been easily available. However, a relatively new statistical methodology is well suited to include such time‐dependent predictors in transition to psychosis analysis. This methodology is called joint modelling and has recently been incorporated in mainstream statistical software. This paper describes this methodology and demonstrates its usefulness using data from one of the pioneering studies on transition to psychosis.