Molecular mechanisms for the antidepressant-like effects of a low-dose ketamine treatment in a DFP-based rat model for Gulf War Illness

Exposure to organophosphates (OP) during the First Gulf War is among one of the factors for Gulf War Illness (GWI) development in veterans and it has been challenging to treat GWI symptoms with existing therapies. Ketamine produces a rapid-onset and sustained antidepressant response, but there is no evidence whether ketamine treatment is effective for GWI depression. Repeated, low-dose exposure to diisopropyl fluorophosphate (DFP) mimic Gulf War related OP exposures and produces a chronic depressive state in rats. In this study, DFP-exposed rats treated with ketamine (10 mg/kg, i.p.) exhibited antidepressant-like effect on the Forced Swim Test at 1-h. This effect persisted at 24-h post ketamine, a time-point by which it is eliminated from the brain suggesting involvement of mechanisms that affect long-term synaptic plasticity. Western blot analysis showed significantly lower Brain-Derived Neurotrophic Factor (BDNF) levels in DFP rat brains. Ketamine produced a nonsignificant increase in BDNF expression at 1-h but produced a larger, significant (2.2-fold) increase at 24-h in DFP rats. We previously reported chronic hippocampal calcium elevations ([Ca²⁺]_i) in DFP rats. Ketamine-treated DFP rats exhibited significantly lower [Ca²⁺]_i at 1-h but not at 24-h. Interestingly, treatment with ANA-12, a TrkB-BDNF receptor antagonist, in DFP rats blunted ketamine’s antidepressant-like effect at 24-h but not at 1-h. These experiments suggest that in a rat model of DFP-induced depression, inhibition of the NMDAR-Ca²⁺ contributes to the rapid-onset antidepressant effects of ketamine while the antidepressant actions that persisted at 24-h post ketamine administration involve upregulation of BDNF signaling.     

细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及 龈沟液炎症因子的影响

目的 探讨细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及龈沟液炎症因子的影响。方法 选取 2019 年 1 月~2021 年 8 月杭州市萧山区中医院接诊的 96 例慢性牙周炎患者作为研究对象。以双色球法将患者 分为对照组和试验组，每组各 48 例。对照组患者在常规治疗基础上加用米诺环素，试验组患者在对照组治疗 基础上加用细辛碎补汤。比较两组患者的临床疗效、牙周指标、龈沟液炎症因子及不良反应发生情况。结果 试 验组患者总有效率显著高于对照组（P<0.05）。治疗后两组患者的探诊深度、菌斑指数、探诊出血指数、龈沟 液 C–反应蛋白、肿瘤坏死因子–α 及白介素–6 水平均显著低于本组治疗前（均 P<0.05），且试验组以上指标均 显著低于对照组（均 P<0.05）。两组患者不良反应发生率比较差异无统计学意义（χ2 =0.154，P=0.695）。结论 细 辛碎补汤联合米诺环素可有效提高慢性牙周炎患者疗效，改善牙周指标，其作用机制可能与降低龈沟液炎症 因子有关。     

Evidence of altered Th17 pathway signatures in the cerebrospinal fluid of patients with Guillain Barré Syndrome

Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barré Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.     

Utility of heavily T2-weighted MR myelography as the first step in CSF leak detection and the planning of epidural blood patches

Heavily T2-weighted MR myelography (HT2W-MRM) is emerging as an alternative approach for detection and follow up of CSF leaks. We aimed to assess epidural blood patch (EBP) treatment outcome when using HT2W-MRM as the primary modality for detecting CSF leak and planning EBP placement in routine clinical practice. Since 2018, patients at our institute suspected of having CSF leak, routinely HT2W-MRM instead of CT myelography to determine presence of the leak and identify the EBP target site. Fifty-nine consecutive patients suspected of having a CSF leak underwent HT2W-MRM. After excluding patients with subdural hematoma and poor image quality, 26 (10 men, 16 women; mean age 44.92 ± 12.6 years) patients were included in this study. Patients received EBP on the basis of HT2W-MRM assessments and clinical assessment. Imaging findings and clinical outcome were evaluated. CSF leak was identified in 21 patients (80.8%, 21/26) based HT2W-MRM. Most cases were graded on a confidence scale as CSF leak definitely (n = 13) or probably (n = 3) present. Successful clinical EBP treatment was achieved in 14 of 17 patients (82.4%) after first targeted EBP, and patient symptoms significantly improved after treatment (numerical rating score 6.4 before EBP, 1.3 after EBP, P < 0.001). HT2W-MRM based EBP are the rational and effective choices for CSF leak treatment in routine clinical practice.     

COVID-19, SARS and MERS: A neurological perspective

Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.     

经肺泡灌洗液高通量测序诊断婴儿肺孢子菌肺炎1 例并文献复习

目的探讨肺孢子菌肺炎的病因、临床表现、病原学诊断和治疗。方法回顾分析1例肺孢子菌肺炎患儿的临床资料。结果患儿,男,2个月20天,临床表现为慢性咳嗽、气促、烦躁、低氧血症;肺部影像呈双肺弥漫性浸润改变;经支气管镜术取肺泡灌洗液进行宏基因高通量测序后证实为肺孢子菌感染。确诊后予甲氧苄胺嘧啶-磺胺甲噁唑(TMP-SMZ)治疗,临床症状基本消失,肺部 CT明显好转。结论肺泡灌洗液行宏基因高通量测序可诊断肺孢子菌肺炎。     

Gas,tubes and flow

Optimizing the flow of both liquids and gases is crucial to many areas of anaesthetic and critical care practice. In this article, we describe the physical principles that govern the flow of gases and present scenarios from clinical practice to illustrate these concepts. The difference between laminar and turbulent flow is explained, along with the factors that determine the nature of the fluid flow. The Venturi effect, Bernoulli principle and Coanda effect are also described with reference to their clinical applications and their relevance to medical devices.     

Cerebrospinal fluid hypotension following fall in a child: Case report

CSF hypotension arises in the context of a leak of CSF which causes negative intracranial pressure. Sacral fractures result from high-energy trauma which are frequently underdiagnosed. A ten-year-old boy presented with hip pain, after a fall. He mobilized both lower limbs, reported no leg pain, irradiation nor lack of sphincter control. The neurological examination was normal. When asked to stand, he began biparietal headache, nausea and vomiting, which improved laying down. CT scan showed an occult intrasacral meningocele; the MRI revealed collections of CSF along the spine, a S3 fracture with potential laceration of the meningocele and opening of a CSF fistula. Our diagnosis was the CSF hypotension, secondary to the fistula opening. The diagnosis was challenging. The child first presented with symptoms of CSF hypotension without evident cause. The discovery of the meningocele led us to hypothesize the opening of a fistula, a rare diagnosis, later confirmed by MRI.     

限制液体复苏在创伤失血性休克患者急救中的应用效果

目的观察限制液体复苏在创伤失血性休克患者急救中的应用效果。方法选取福建医科大学附属南平市第一医院收治的76例创伤失血性休克患者作为研究对象,依据入院前后顺序将其分为对照组(n=38)和观察组(n=38),对照组接受积极液体复苏方案,观察组接受限制液体复苏方案,比较两组治愈率、治疗后各指标水平、液体输入量及并发症发生情况。结果观察组治愈率明显高于对照组,液体输入量明显低于对照组,差异有统计学意义(P<0.05);治疗后观察组乳酸、凝血酶原时间、平均动脉压及血红蛋白水平均明显优于对照组,差异均有统计学意义(P<0.05);观察组并发症发生率为15.8%,明显低于对照组的36.8%,差异有统计学意义(P<0.05)。结论限制液体复苏应用在创伤失血性休克患者急救中,可提高患者的治愈率,改善乳酸、凝血酶原时间等指标水平,降低并发症发生率的效果优于积极液体复苏应用效果。