儿童肺炎克雷伯菌血流感染临床特征及菌株药物敏感性分析

摘要：目的 探讨儿童肺炎克雷伯菌血流感染(Klebsiella pneumoniae bloodstream infection, KPBSI)临床特征及肺炎克雷伯 菌(Klebsiella pneumoniae, KP)对常用抗菌药物的敏感性，为儿童KPBSI合理治疗提供参考。方法 回顾性分析2014年1月至2019 年12月在重庆医科大学附属儿童医院住院的KPBSI患儿临床资料。结果 共纳入110例患儿，64例(58.2%)为院内感染，72例 (65.5%)有基础疾病，以血液系统肿瘤最多见。110例患儿PRISM Ⅲ评分为16.0(7.0~20.8)，其中74例(67.3%)发生脓毒症，15例 (13.6%)发生脓毒性休克，18例(16.4%)发生呼吸衰竭，15例(13.6%)需有创机械通气，院内死亡共13例(11.8%)。KP菌株对阿米卡 星、碳青霉烯类抗菌药物敏感率＞90%，对头孢噻肟、头孢曲松和头孢他啶的敏感率分别为58.3%、60.9%和70.9%，对头孢哌 酮/舒巴坦和哌拉西林/他唑巴坦的敏感率分别为59.5%和82.7%。检出ESBLs+菌株39株(39/86，45.3%)，耐碳青霉烯类肺炎克雷 伯菌(CRKP)菌株10株(10/110，9.1%)，ESBLs+KP菌株和CRKP在各年龄组间分布无统计学差异。结论 儿童KPBSI多见于有基 础疾病的患儿，脓毒症、脓毒性休克和呼吸衰竭发生率高；KP菌株对头孢他啶和哌拉西林/他唑巴坦敏感性较高，可经验性治 疗轻症KPBSI患儿。     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

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Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease

ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.     

The endogenous inflammatory reflex inhibits the inflammatory response to different immune challenges in mice

The splanchnic anti-inflammatory pathway, the efferent arm of the endogenous inflammatory reflex, has been shown to suppress the acute inflammatory response of rats to systemic lipopolysaccharide (LPS). Here we show for the first time that this applies also to mice, and that the reflex may be engaged by a range of inflammatory stimuli. Experiments were performed on mice under deep anaesthesia. Half the animals were subjected to bilateral section of the splanchnic sympathetic nerves, to disconnect the splanchnic anti-inflammatory pathway, while the remainder underwent a sham operation. Mice were then challenged intravenously with one of three inflammatory stimuli: the toll-like receptor (TLR)-4 agonist, LPS (60 µg/kg), the TLR-3 agonist Polyinosinic:polycytidylic acid (Poly I:C, 1 mg/kg) or the TLR-2 and -6 agonist dipalmitoyl-S-glyceryl cysteine (Pam2cys, 34 µg/kg). Ninety minutes later, blood was sampled by cardiac puncture for serum cytokine analysis. The splanchnic anti-inflammatory reflex action was assessed by comparing cytokine levels between animals with cut versus those with intact splanchnic nerves. A consistent pattern emerged: Tumor necrosis factor (TNF) levels in response to all three challenges were raised by prior splanchnic nerve section, while levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were reduced. The raised TNF:IL-10 ratio after splanchnic nerve section indicates an enhanced inflammatory state when the reflex is disabled. These findings show for the first time that the inflammatory reflex drives a coordinated anti-inflammatory action also in mice, and demonstrate that its anti-inflammatory action is engaged, in similar fashion, by inflammatory stimuli mimicking a range of bacterial and viral infections.     

磁敏感加权成像黑质“燕尾征”在帕金森病中的诊断价值

目的:探讨3.0 T磁敏感加权成像(susceptibility weighted imaging,SWI)中"燕尾征"缺失在帕金森病(Parkinson's dis-ease,PD)的诊断价值并分析黑质小体-1 (nigrosome-1)可视化与PD患者临床资料的相关性.方法:收集2017年9月至2019年11月于重庆医科大学附属第一医院神经内科住院的50例PD患者及年龄、性别与之匹配的57例非PD患者.所有受试者均接受3.0 T头颅SWI检查.在获得的SWI图像上,由2名临床医师采用盲法独立对双侧"燕尾征"进行评估.一侧"燕尾征"缺失即判定为PD.计算"燕尾征"缺失诊断PD的灵敏度、特异度、预测值和准确度,并分析nigrosome-1可视化与PD患者临床资料的相关性.结果:以临床诊断作为金标准,45例PD患者判断正确,评估者之间的一致性很高(k=0.963,P=0.000)."燕尾征"缺失诊断PD的灵敏度为90.0％,特异度为91.2％,阳性预测值为90.0％,阴性预测值为91.2％,准确度为90.7％.44例PD患者临床症状不对称,其中32例患者nigrosome-1可视化不对称.PD患者nigrosome-1可视化偏侧和临床症状偏侧比较差异无统计学意义(x2=5.756,P=0.056).11例PD患者双侧nigrosome-1全部缺失,纳入全部缺失组,其余PD患者为非全部缺失组.全部缺失组和非全部缺失组患者的汉密尔顿抑郁量表评分差异有统计学意义(U=126.500,P=-0.038),而病程、帕金森病统一评定量表第Ⅲ部分、改良Hoehn-Yahr(H-Y)分级、简易智能状态量表和蒙特利尔认知评估量表评分差异均无统计学意义(P=0.768、0.140、0.839、0.054、0.067).结论:"燕尾征"缺失诊断PD的准确率较高,缺失程度可能与PD患者的抑郁程度有关,对PD的诊断有一定参考价值.     

HLA-B evolutionary divergence is associated with outcomes after SARS-CoV-2 infection

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham’s distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control.