Perception of induced bronchoconstriction in a community sample of adolescents

BACKGROUND: Poor perception of asthma symptoms has been cited as a risk factor for asthma death, yet there is no consensus as to the best way to characterize perception, and little is known about perception in normative samples. Hypoperceivers are of clinical interest because of risks of undertreatment; hyperperceivers are at risk for adverse iatrogenic effects caused by overtreatment. OBJECTIVE: This study investigates perception of methacholine-induced bronchoconstriction in 175 adolescents. METHODS: Breathlessness was rated after each inhalation by using the Borg scale. Perception groups were calculated on the basis of change from placebo Borg to high Borg scores (perception score at the highest methacholine dose). Subjects were called hypoperceivers if their Borg change score was greater than 1 SD below the mean for their FEV(1) group, hyperperceivers if their Borg change score was greater than 1 SD above the mean for their FEV(1) group, and accurate perceivers otherwise. RESULTS: For subjects with an FEV(1) drop of less than 10%, accurate perceivers had a change in Borg score of 1.4 or less, and hyperperceivers had a change of greater than 1.4. For a drop in FEV(1) between 10% and 19%, hypoperceivers had a change in Borg score of less than 0.2, accurate perceivers had a change between 0.2 and 2.1, and hyperperceivers had a change of greater than 2.1. For those with an FEV(1) drop of 20% or greater, hypoperceivers had a Borg change of less than 0.2, accurate perceivers had a change between 0.2 and 2.6, and hyperperceivers had a change of greater than 2.6. No differences in age, sex, placebo Borg ratings, baseline pulmonary functions, PC(20) values, or psychologic variables were found among perception groups. CONCLUSION: This study provides reference Borg values during methacholine challenge for 175 community adolescents.     

Familial association between allergic disorders and depression in adult Finnish twins

Clinical studies have shown a relationship between allergic disorders and depression, panic disorder, attention deficit/hyperactivity disorder, and social anxiety for a significant subset of patients with these disorders. The nature of the relationship, whether due to shared environmental or biologic vulnerabilities or as a result of the stress of chronic illness, has been less clear. By examining the covariance of atopic disorders and depressive symptoms in a community sample of monozygotic (MZ) and dizygotic (DZ) twins, the contribution of genetic and/or shared environmental etiological factors can be established. A Finnish sample of 1337 MZ and 2506 DZ twin pairs, ages 33-60 years, was sent questionnaires inquiring about history of asthma, eczema, and atopic rhinitis, as well as the Beck Depression Inventory (BDI). The nature of the covariation between twins of these symptoms was investigated by fitting competing genetic and environmental models. Within-person correlation between atopic symptoms and BDI was 0.103 (P < 0.001) for the total sample. Using the Mx statistical modeling program to fit the data to competing quantitative genetic models, the best fitting model estimated that 64% of the association between atopy and BDI was due to shared familial vulnerability, primarily additive genetic influences. Although the measures for allergic disorders and depression are crude, this study supports the hypothesis that there is a small shared genetic risk for atopic and depressive symptoms, and if replicated, may open research for common mechanisms between allergic and depressive disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:146-153, 2000.     

The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim

The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial breast and ovarian cancer and in the general population. All tested Ashkenazi mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a similar allelic pattern. We extended our analysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200 Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented by direct DNA sequencing of abnormally migrating bands were employed. Four of Moroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrier of the 185delAG mutation. BRCA1 allelic patterns were determined for four of these individuals and for 12 additional non-Ashkenazi 185delAG mutation carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals shared the common 'Ashkenazi haplotype', four had a closely related pattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern. We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazi populations at rates comparable with that of Ashkenazim. The majority of Jewish 185delAG mutation carriers have a common allelic pattern, supporting the founder effect notion, but dating the mutation's origin to an earlier date than currently estimated. However, the different allelic pattern at the BRCA1 locus even in some Jewish mutation carriers, might suggest that the mutation arose independently.      

Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.     

Subjective cognitive complaints and neuropsychological performance in former smokers with and without chronic obstructive pulmonary disease

Objective: This study examined the association of perceived cognitive difficulties with objective cognitive performance in former smokers. We hypothesized that greater perceived cognitive difficulties would be associated with poorer performance on objective executive and memory tasks.

Method: Participants were 95 former smokers recruited from the COPDGene study. They completed questionnaires (including the Cognitive Difficulties Scale [CDS] and the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment, and pulmonary function testing. Pearson correlations and t-tests were conducted to examine the bivariate association of the CDS (total score and subscales for attention/concentration, praxis, delayed recall, orientation for persons, temporal orientation, and prospective memory) with each domain of objective cognitive functioning (memory recall, executive functioning/processing speed, visuospatial processing, and language). Simultaneous multiple linear regression was used to further examine all statistically significant bivariate associations. The following covariates were included in all regression models: age, sex, pack-years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria).

Results: In regression models, greater perceived cognitive difficulties overall (using CDS total score) were associated with poorer performance on executive functioning/processing speed tasks (b = ?0.07, SE = 0.03, p = .037). Greater perceived cognitive difficulties on the CDS praxis subscale were associated with poorer performance on executive functioning/processing speed tasks (b = ?3.65, SE = 1.25, p = .005), memory recall tasks (b = ?4.60, SE = 1.75, p = .010), and language tasks (b = ?3.89, SE = 1.39, p = .006).

Conclusions: Clinicians should be aware that cognitive complaints may be indicative of problems with the executive functioning/processing speed and memory of former smokers with and without COPD.     

2008-2018年湖北省食物中毒事件流行特征分析

目的分析湖北省食物中毒事件流行病学特征,为制定防控策略提供科学依据。方法对《突发公共卫生事件管理信息系统》中报告的食物中毒事件进行描述性分析。结果共报告95起食物中毒事件,较大级别最多(占44.21%),病死率为15.71%;细菌性食物中毒事件数和发病数最多,分别占43.16%、69.66%,真菌性食物中毒死亡数最多(占59.72%);家庭、集体食堂、饮食服务单位是食物中毒事件发生的主要场所(占88.42%),家庭主要为真菌性食物中毒(占60.46%),集体食堂主要为细菌性食物中毒(70.97%);6-9月为食物中毒事件的高发期,主要由细菌性和真菌性引起(占87.72%);报告事件数居前五位的市州为恩施州(占22.11%)、十堰市(占18.95%)、襄阳市(占12.63%)、黄石市和宜昌市(各占9.47%);恩施州和十堰市主要以真菌性食物中毒高发,分别占该地区总事件数的66.67%、50.00%。结论较大级别事件居多,且其病死率高;细菌性是引起食物中毒的主要因素,真菌性是引起死亡的主要因素;家庭是发生食物中毒事件的主要场所,且以真菌性居多;集体食堂食物中毒事件病例数多,且以细菌性居多;...     

2013-2017年江苏省动物性食品中硝基呋喃类代谢物膳食暴露分析

目的了解2013-2017年江苏省动物性食品中硝基呋喃类代谢物污染状况,分析其膳食暴露水平,为保障食品安全、加强监管提供科学依据。方法根据国家食品安全风险监测工作要求,按照标准操作程序检测1682份样品硝基呋喃类代谢物残留,结合居民食物消费状况,使用@RISK软件建立污染物累积膳食暴露模型,分析其人体膳食暴露风险。结果被硝基呋喃类代谢物污染的动物性食品主要为鸡蛋、鸡肉和水产品,污染物总体检出率为3.98%,其中鸡肉中AMOZ检出值高达144.0μg/kg,鱼肉中SEM最高检出值为41.0μg/kg。每人每天膳食中该类污染物平均暴露量为0.13μg,即2.03×10^-3μg/kg BW,污染物P₉₉暴露量为1.01μg,即1.59×10^-2μg/kg BW。结论膳食暴露评价结果显示此范围内硝基呋喃类代谢物对人体健康损害很小,但违规使用硝基呋喃类药物的现象比较严重,因此建立健全兽药监控管理体系,定期开展动物性食品兽药残留风险评估工作,构建动物性食品安全风险预警系统将有效降低人体污染物暴露水平。