Free light chains as an emerging biomarker in saliva: Biological variability and comparisons with salivary IgA and steroid hormones

BackgroundSalivary free light chains (FLCs) are an emerging biomarker in health and behavioural research. However, little is known regarding biological variability of salivary FLCs and how they relate to other established salivary biomarkers. This study aimed to investigate the diurnal and day-to-day variation of salivary FLCs and their relationship with salivary IgA and steroid hormones.MethodsA total of 46 healthy adults participated in studies exploring the biological variability of FLCs. Diurnal variation was investigated by collecting saliva samples immediately upon waking, 0.5 h, 3 h, 6 h, 9 h and 14 h post-waking. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Between-day variation in FLCs and IgA was assessed by collecting saliva samples immediately upon waking for seven consecutive days. Participants underwent a dental examination to exclude oral health as a potential confounding variable. Within and between-person day-to day variation was explored in relation to a range of different factors: awakening time, sleep, exercise, well-being and alcohol consumption.ResultsSalivary secretion rates of FLCs decreased following waking and up to 3 h post-waking and then plateaued. This same pattern was observed for IgA. DHEA was stable upon waking and higher levels were seen in the morning with significantly lower levels thereafter. Cortisol levels significantly increased 0.5 h post-waking then continued to decline across the day. FLCs were significantly correlated with IgA but not cortisol or DHEA. Both FLCs and IgA parameters showed day-to-day variability, with coefficients of variation ≥ 40%. Earlier waking time was significantly correlated with higher FLC and IgA secretion rates. Inter-person differences in saliva parameter variability were observed but the degree of variation in FLCs and IgA was related within person. Inter-person day-to-day variation appeared to be uninfluenced by lifestyle or behavioural factors.ConclusionsSaliva FLCs secretion exhibits diurnal fluctuation that mirrors IgA fluctuation. Findings strongly indicate salivary FLC secretion is orchestrated by local plasma cells. FLCs and IgA both showed notable variability day-to-day, which was similar within person and influenced by awakening time. FLCs offer a promising adjunct to IgA in the measurement of oral immune activation.     

超分子水杨酸联合强脉冲光治疗中重度痤疮的疗效分析

目的分析超分子水杨酸联合强脉冲光治疗中重度寻常痤疮的安全性及有效性。方法回顾性总结2015年12月-2017年12月在首都医科大学附属北京佑安医院皮肤科就诊的60例中重度痤疮患者,分为两组,每组各30例患者,分别给予强脉冲光联合30%超分子水杨酸治疗及单纯30%超分子水杨酸治疗。试验组首先给予强脉冲光治疗,根据患者皮损特点、肤色、耐受度选择治疗参数,炎症明显处治疗2次;强脉冲光治疗结束后,清洗面部,全面部涂抹30%超分子水杨酸,慢慢揉搓治疗区域,应用蒸馏水防止干燥且保证水杨酸缓慢释放,持续时间根据患者的耐受程度,一般为10~15 min,每月治疗1次,共治疗1次。对照组仅给予30%超分子水杨酸治疗,每月治疗1次,共治疗4次。治疗后1个月门诊随访。结果试验组的有效率(63.33%)高于对照组(36.67%);试验组治疗后粉刺、炎症丘疹及脓疱、囊肿结节数量比治疗前明显减低。结论超分子水杨酸联合强脉冲光治疗中重度痤疮疗效较好,减少患者治疗周期,未增加不良反应的发生。     

红光与常规治疗对成人急性化脓性中耳炎的协调作用

目的观察在常规治疗基础上联合红光照射对成人急性化脓性中耳炎(acute suppurative otitis media,ASOM)临床疗效的影响。方法确诊为急性化脓性中耳炎的患者62例68耳,随机分为对照组31例33耳,使用抗生素滴耳、口服黏液促排剂;试验组31例35耳,在此基础上联合红光照射治疗。治疗后7和14 d比较两组患者临床症状改善情况、听力恢复情况;记录外周血的TNF-α、IL-2、IL-6、IL-10、IL-1β;以及耳道内致病菌株数。结果治疗后7和14 d,试验组临床症状改善情况和听力恢复情况(气导听阈均值、气-骨导听阈差均值)分别优于相同治疗时间点的对照组(P<0.05);治疗第7天,对照组外周血的TNF-α和IL-6较治疗前有显著下降(P<0.05),试验组外周血的TNF-α、IL-2、IL-6、IL-10、IL-1β均较治疗前有显著下降(P<0.05)。试验组与对照组相比,除IL-10外,其余炎性因子下降幅度均低于对照组(P<0.05);治疗第14天,两组耳道内致病菌株数显著降低(P<0.05),且试验组显著低于对照组(P<0.05)。结论对于ASOM患者,在常规抗生素联合黏液促排剂治疗的基础上联合红光治疗,可加速鼓室黏膜恢复正常、提高听力改善速度和程度,其机制可能与红光协同消除病原菌、加速降低多项炎性因子水平有关。联合红光治疗对于抗生素疗效不佳而导致病情恢复较慢的患者是很好的选择。     

Elevated serum neurofilament light chain in children autism spectrum disorder: A case control study

ObjectiveWe aimed to assess serum neurofilament light chain (sNfL) levels in autism spectrum disorder (ASD) and to investigate whether they are related to the severity of disease.MethodsThe cohorts consisted of 166 children aged 3–8 (83 children diagnosed with ASD and 83 children with typically-developing). sNfL were analyzed using Single Molecule Array (Simoa) technology. ASD symptom severity was assessed according to the Chinese version of the Childhood Autism Rating Scale (CARS) score.ResultsThe mean age of those included ASD was 5.1 years (standard deviations [S.D.]: 1.7) and 78.3 % were boys. The mean (SD) sNfL concentrations were significantly (P < 0.001) higher in ASD than in TP children (10.2[5.0] pg/mL and 7.1[3.2]pg/mL). For each 1 pg/mL increase of sNfL, the risk of ASD would increase by 19 % (with the OR _unadjusted of 1.19 [95 % CI 1.10–1.29], P < 0.001) and 11 % (with the OR _adjusted of 1.11 [1.03–1.23], P < 0.001), respectively. sNfL concentrations in children with severe ASD were higher than in those children with mild-to-moderate ASD (12.4[5.1] pg/mL vs. 8.3[4.2]pg/mL; P < 0.001). Among ASD cases, each 1 pg/mL increase of sNfL is associated with 20 % higher unadjusted or 11 % higher adjusted odds, respectively, of severe (vs. mild-to-moderate) ASD.ConclusionsThe data showed that sNfL was elevated in ASD and related to symptom severity, suggesting that sNfL may play a role in ASD progression.     

Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system

Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.     

Quality of Life Impacts of Bright Light Treatment,Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial

Objective:Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome.Methods:This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression.Results:Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores.Conclusion:The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.