脉冲振荡肺功能技术的应用新进展

脉冲振荡技术是一项具有发展前景和临床实用价值的肺功能测定技术。该技术在诊断气道阻塞性疾病方面具有较高的敏感性，并能区分气道阻塞的部位，在气道反应性检查和气道阻塞性疾病的治疗评估等方面具有较高的优势。     

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

Objective

We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD.

Methods

We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed.

Results

Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus.

Conclusion

These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.     

Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV‐infected older adults

Combination antiretroviral therapy transformed human immunodefiency virus (HIV)‐infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV‐infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high‐resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV‐related cognitive impairments. HIV‐infected adults and individually matched controls completed 3‐Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel‐based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV‐infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV‐infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV‐associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV‐associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp 36:897–910, 2015. © 2014 Wiley Periodicals, Inc.     

高频振荡呼吸机治疗新生儿呼吸衰竭的临床疗效

目的：分析探讨高频振荡呼吸机治疗新生儿呼吸衰竭的临床效果。方法2010年1月—2015年1月期间,该院共接收呼吸衰竭的新生儿52例,选择此52例患儿作为此次试验的临床研究对象,并以随机数字表法为分组依据将其平均分配为对照组以及试验组,对照组26例患儿接受常频机械通气呼吸机治疗,试验组患儿则接受高频振荡通气呼吸机治疗,治疗后比较两组患儿的PH、PCO、PO、FiO四项指标水平以及两组患者在治疗时间、住院时间、上机花费上是否存在差异。结果两组患儿经过合理的治疗以及悉心护理后,全部存活出院,但在上机治疗1 d后PCO、PO、FiO三项指标水平上对照组患儿明显不及试验组;且对照组患儿上机治疗时间为（127.5±32.10） h,试验组患儿上机治疗时间为（89.3±13.34） h;另外,在住院时间以及上机花费上,对照组也明显高于试验组,以上各项数据的差异有统计学意义（P＜0.05）。结论应用高频振荡呼吸机治疗新生儿的呼吸衰竭,可以使患儿呼吸功能得到明显改善,节省治疗、住院时间以及治疗费用。     

Altered modulation of gamma oscillation frequency by speed of visual motion in children with autism spectrum disorders

Background

Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50–120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of gamma oscillations is mediated by level of excitation of the fast-spiking inhibitory basket cells recruited by increasing strength of excitatory input. Therefore, the experimental manipulations affecting gamma frequency may throw light on inhibitory networks dysfunction in ASD.

Methods

Here, we used magnetoencephalography (MEG) to investigate modulation of visual gamma oscillation frequency by speed of drifting annular gratings (1.2, 3.6, 6.0 °/s) in 21 boys with ASD and 26 typically developing boys aged 7–15 years. Multitaper method was used for analysis of spectra of gamma power change upon stimulus presentation and permutation test was applied for statistical comparisons. We also assessed in our participants visual orientation discrimination thresholds, which are thought to depend on excitability of inhibitory networks in the visual cortex.

Results

Although frequency of the oscillatory gamma response increased with increasing velocity of visual motion in both groups of participants, the velocity effect was reduced in a substantial proportion of children with ASD. The range of velocity-related gamma frequency modulation correlated inversely with the ability to discriminate oblique line orientation in the ASD group, while no such correlation has been observed in the group of typically developing participants.

Conclusions

Our findings suggest that abnormal velocity-related gamma frequency modulation in ASD may constitute a potential biomarker for reduced excitability of fast-spiking inhibitory neurons in a subset of children with ASD.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9121-x) contains supplementary material, which is available to authorized users.     

Population Balance Model for Simulation of the Supersaturation–Precipitation Behavior of Drugs in Supersaturable Solid Forms

We developed a simulation method to describe in vitro drug concentration?time profiles under supersaturated conditions. In a nonsink dissolution test of carbamazepine polymorphic form III (CBZ_III), a model supersaturable solid, the concentration of carbamazepine reached a supersaturated state against its dihydrate form (CBZ_DH). After a certain period, de-supersaturation due to the precipitation of CBZ_DH was observed. In the simulation of this typical dissolution?precipitation profile, the precipitation process of CBZ_DH was simulated by a population balance model in which the rates of primary/secondary nucleation and growth of CBZ_DH were considered. Six rate constants in the precipitation model were determined from de-supersaturation profiles in unseeded isothermal crystallization experiments of CBZ_DH. The dissolution process of CBZ_III was modeled on the basis of its dissolution profile under a sink condition. The simulated concentration versus time curves satisfactorily reproduced the characteristics of dissolution, supersaturation, and precipitation behavior of the model drug. The presented method will enable rational design of formulations and accurate prediction of the oral absorbability of drugs in supersaturable solid forms.     

Catamenial Acute Intermittent Porphyria Managed with GnRH Analogues and Estrogen and Progesterone Add-back Therapy

BackgroundCatamenial precipitation of attacks of acute intermittent porphyria (AIP) is commonly treated with gonadotropin-releasing hormone analogues (GnRHas). However, this leads to various adverse effects that might necessitate “add-back” therapy with estrogen. The literature on the efficacy and safety of such therapy is scarce.CaseA 15-year-old girl presented to us with recurrent catamenial attacks of AIP. GnRHa therapy led to near-complete amelioration of the episodes but her bone density worsened as an adverse effect. To circumvent this, low-dose estrogen was added to her regimen as an “add-back” therapy, which was later coupled with cyclical progesterone. She continues to do well using this regimen, with no new episodes.Summary and ConclusionGnRHa therapy with estrogen “add-back” is an attractive option for treating catamenial AIP episodes.     

Correlations between forced oscillation technique parameters and pulmonary densitovolumetry values in patients with acromegaly

The aims of this study were to evaluate the forced oscillation technique (FOT) and pulmonary densitovolumetry in acromegalic patients and to examine the correlations between these findings. In this cross-sectional study, 29 non-smoking acromegalic patients and 17 paired controls were subjected to the FOT and quantification of lung volume using multidetector computed tomography (Q-MDCT). Compared with the controls, the acromegalic patients had a higher value for resonance frequency [15.3 (10.9-19.7) vs 11.4 (9.05-17.6) Hz, P=0.023] and a lower value for mean reactance [0.32 (0.21-0.64) vs 0.49 (0.34-0.96) cm H₂O/L/s², P=0.005]. In inspiratory Q-MDCT, the acromegalic patients had higher percentages of total lung volume (TLV) for nonaerated and poorly aerated areas [0.42% (0.30-0.51%) vs 0.25% (0.20-0.32%), P=0.039 and 3.25% (2.48-3.46%) vs 1.70% (1.45-2.15%), P=0.001, respectively]. Furthermore, the acromegalic patients had higher values for total lung mass in both inspiratory and expiratory Q-MDCT [821 (635-923) vs 696 (599-769) g, P=0.021 and 844 (650-945) vs 637 (536-736) g, P=0.009, respectively]. In inspiratory Q-MDCT, TLV showed significant correlations with all FOT parameters. The TLV of hyperaerated areas showed significant correlations with intercept resistance (r_s=−0.602, P<0.001) and mean resistance (r_s=−0.580, P<0.001). These data showed that acromegalic patients have increased amounts of lung tissue as well as nonaerated and poorly aerated areas. Functionally, there was a loss of homogeneity of the respiratory system. Moreover, there were correlations between the structural and functional findings of the respiratory system, consistent with the pathophysiology of the disease.     

Overcoming the Challenges of Low Drug Solubility in the Intravenous Formulation of Solithromycin

Solithromycin is a fluoro-ketolide (a fourth-generation macrolide) antibiotic that has been undergoing clinical trials for the treatment of community-acquired bacterial pneumonia. In this study, development of the tri-amino acid–buffered solithromycin intravenous (IV) formulation was performed to minimize the occurrence of infusion-associated local adverse events (infusion-site pain or phlebitis) observed in patients who received the tartaric acid–buffered IV formulation with a lower buffered capacity during phase I clinical trials. Development of the tri-amino acids–buffered solithromycin IV formulation was achieved using a dynamic in vitro precipitation model. Computational modeling also supports the superiority of the amino acid-buffered formulation over the tartaric aid–buffered formulation.     

Relative entropy minimizing noisy non-linear neural network to approximate stochastic processes

A method is provided for designing and training noise-driven recurrent neural networks as models of stochastic processes. The method unifies and generalizes two known separate modeling approaches, Echo State Networks (ESN) and Linear Inverse Modeling (LIM), under the common principle of relative entropy minimization. The power of the new method is demonstrated on a stochastic approximation of the El Niño phenomenon studied in climate research.