从肝脾论治成年女性特应性皮炎

目的:特应性皮炎的发病及治疗存在很大的异质性,在治疗方面特别强调个体化治疗,本文主要总结成年女性特应性皮炎的治疗思路和方法。方法:基于肝脾两脏的生理、病理及成年女性特应性皮炎的临床表现,深入分析其病因病机及治疗方法。结果:女性成年特应性皮炎患者常肝脾同病,肝郁脾虚湿蕴和肝郁脾虚血弱是成年女性特应性皮炎的常见证型,临床可采用疏肝健脾祛湿法和疏肝健脾养血法进行治疗。典型病例中采用肝脾同调法不但可以改善患者的皮疹,也可有效缓解瘙痒和不良情绪。结论:肝脾同调法是治疗成年女性特应性皮炎的有效方法。     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Paresthesia‐Free Spinal Nerve Root Stimulation for the Treatment of Chronic Neuropathic Pain

ObjectiveStimulation of the dorsal spinal roots, or spinal nerve root stimulation (SNRS), is a neuromodulation modality that can target pain within specific dermatomal distributions. The use of paresthesia-free stimulation has been described with conventional dorsal column spinal cord stimulation, although has yet to be described for SNRS. This objective of this study was to investigate the efficacy of paresthesia-free high-frequency (1000–1200 Hz) SNRS in the treatment of intractable, dermatomal neuropathic pain.Materials and MethodsA retrospective chart review was performed on 14 patients implanted with SNRS in varying distributions: Ten patients initially received tonic stimulation and crossed over to a paresthesia-free paradigm and four patients received only paresthesia-free stimulation. The primary outcome was reduction in pain severity (visual analog scale [VAS]), measured at baseline and follow-up to 24 months with paresthesia-free stimulation.ResultsAll 14 patients who received paresthesia-free stimulation had significant improvement in pain severity at a mean follow-up of 1.39 ± 0.15 years (VAS 7.46 at baseline vs. 3.25 at most recent follow-up, p < 0.001). Ten patients were initially treated with tonic stimulation and crossed over to paresthesia-free stimulation after a mean of 61.7 months. Baseline pain in these crossover patients was significantly improved at last follow-up with tonic stimulation (VAS 7.65 at baseline vs. 2.83 at 48 months, p < 0.001), although all patients developed uncomfortable paresthesias. There was no significant difference in pain severity between patients receiving tonic and paresthesia-free stimulation.ConclusionsWe present real-world outcomes of patients with intractable dermatomal neuropathic pain treated with paresthesia-free, high-frequency SNRS. We demonstrate its effectiveness in providing pain reduction at a level comparable to tonic SNRS up to 24 months follow-up, without producing uncomfortable paresthesias.     

Wireless Connectivity for People with Hearing Loss: The Acoustic Transparency of Waterproof Smartphone Cases

Phone use is a critical communication event in many people''s lives. Audiologists have aimed to assist individuals with hearing loss and phone usage through the use of technology and counseling. To counsel effectively, all contributions to hearing difficulty on the phone must be considered, including the effects of smartphone cases. The purpose of this study was to evaluate the effects on dB output caused by waterproof smartphone cases that cover the ear-level speaker. One waterproof case was tested with three smartphones, two iPhones, and one Android. A second waterproof case was tested with the two iPhones. Results revealed there was significant attenuation of the audio-signal by both waterproof smartphone cases that was great enough in one case/phone combination to potentially result in a complete lack of intelligibility of the signal.     

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

BackgroundDiffuse midline glioma, formerly DIPG (diffuse intrinsic pontine glioma), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated (i) whether direct delivery of adenovirus-expressing cluster of differentiation (CD)40 ligand (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and (ii) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.MethodsSyngeneic gliomas in the brainstems of immunocompetent mice were treated with Ad-CD40L and survival, toxicity, and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient–derived diffuse midline gliomas and immunocompetent models.ResultsExpression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intratumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-sequencing analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with interleukin (IL)-6, IL-1β, and tumor necrosis factor α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for diffuse midline gliomas. Direct intratumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity.ConclusionsVirus-mediated delivery of CD40L has the potential to be effective in treating diffuse midline gliomas without obligatory neuroinflammation-associated toxicity.