Antibody responses against B-cell epitopes of the hypervariable region 1 of hepatitis C virus in self-limiting and chronic human hepatitis C followed-up using consensus peptides.

A rare collection of serum samples from patients with hepatitis C virus (HCV) infection followed up from the onset of clinical symptoms was acquired. RNA corresponding to the hypervariable region 1 (HVR1) of E2 protein of HCV isolated from nine patients was reverse-transcribed, amplified, sequenced, and HVR1 amino acid sequences were deduced. These sequences and a selection of HVR1 amino acid sequences of matching HCV genotypes from protein and translated DNA sequence databanks were used to create the HVR1 amino acid consensus. The degenerated peptides mimicking N- and C-termini of the consensus were synthesized. Most (76%) of 17 patients followed up for the period from 1 week to a minimum of 7 months from the onset of acute symptoms developed antibodies reacting with peptides representing N- and/or C- termini of HVR1. Antibody recognition of the consensus HVR1 peptides indicates that the variability of HVR1 sequence on the protein level is limited with certain conserved structure(s) being untouched. A tendency was observed for a slower development of anti-HVR1 antibody response in patients developing chronic HCV, as compared to those with self-limiting HCV infection.     

Searching for Interactive Effects in the Etiology of Early-Onset Substance Use

This study sought to expand the modest literature investigating gene × environment interactions in the prediction of substance use. Our sample consisted of 591 male twins from the Minnesota Twin Family Study. Their relative genetic risk was estimated from their parents' substance-related diagnoses and their environmental risk from their affiliations at age 11 with social groups likely to either encourage or discourage substance use. At age 14, the boys' own substance use was assessed. We hypothesized both main effects and an interaction between our genetic- and environmental-risk variables in the prediction of substance use by this young age. We further theorized that the boys' inherited risk might take the form of temperament, specifically externalizing tendencies. Using regression analyses and biometrical modeling, we corroborated earlier research by finding evidence for a significant interactive effect in the etiology of substance use. Our results suggest that low levels of environmental risk may buffer against the potentially unfavorable effects of high familial risk; however, when environmental risk is high, the degree of familial risk is consequential. We were not able to support our second hypothesis; rather, temperament predicted substance use only through shared environmental factors.     

Prediction of an unfavourable course of low back pain in general practice: comparison of four instruments

BACKGROUND: Several instruments can be used to identify patients with an unfavourable course of low back pain in general practice. However, it is unclear which instrument is the predictor of outcome. AIM: To compare the predictive performance (that is, calibration and discrimination) of risk estimation by GPs with assessments using the Orebro Musculoskeletal Pain Screening Questionnaire, the Low Back Pain Perception Scale (LBPPS), and a prediction rule developed for this purpose. Design of study: A prospective cohort study with 1-year follow-up. SETTING: General practice in The Netherlands. METHOD: The outcome 'unfavourable course of low back pain' was defined as having no clinically important improvement at minimally 50% of the measurements at 6, 13, 26, and 52 weeks. Logistic regression analyses were used to study associations between potential predictors and outcome. RESULTS: In total, 60 GPs recruited 314 patients to the study (16 patients were excluded from analysis due to missing data on the course of low back pain). Over a third of patients (112/298) showed an unfavourable course of low back pain on follow-up. Risk estimation by GPs, the Orebro questionnaire, the LBPPS, and the prediction rule had discriminative ability (area under the curve) of 0.59 (95% CI [confidence intervals] = 0.52 to 0.66); 0.61 (95% CI = 0.54 to 0.67); 0.59 (95% CI = 0.52 to 0.66); and 0.75 (95% CI = 0.69 to 0.81) respectively. The prediction rule included history of low back pain, self-perceived risk to develop chronic low back pain, no solicitous responses of the patient's partner (as reported by the patient), frequent walking at work, and 'pain catastrophising'. CONCLUSION: Although the prediction rule performed best with regard to calibration and discrimination, it needs to be externally validated. Risk estimation by GPs performs as well as other instruments and, at present, seems to be the best available option.     

Cord serum IgE in relation to family history and as predictor of atopic disease in early infancy

Cord serum IgE was assayed by particle counting immunoassay (PACIA) in an unselected series of European newborns (n = 190; geom mean = 0.37 IU/ml) and a cutoff limit established (≥ 1.20 IU/ml) for prediction of atopy. At control follow-up by questionnaire 18 months after birth, 38 infants (20.0%) had developed definite (9.5%) or probable (10.5%) atopy with a significant predominance of boys ( P < 0.03). Infants with a positive immediate family history (IFH) had a higher risk of developing atopy ( P < 0.0025) and also had a higher incidence of elevated cord IgE ( P < 0.02) than infants with a negative IFH. Maternal atopy influenced cord IgE levels significantly ( P < 0.00005), whereas paternal atopy did not ( P = 0.23). No fetal IgE antibodies against five common allergens could be demonstrated in 36 cord sera tested. Breast-feeding for 3 months was not sufficient to prevent atopic symptoms. The predictive value of cord IgE was high since 26 of 36 newborns (positive predictive value = 72.2 %) with elevated cord IgE had developed atopic symptoms before follow-up. Of the 38 infants who developed atopic symptoms, 26 had elevated cord IgE (sensitivity = 68.4%) compared to only 10 (6.6%) of the 152 atopy-free infants (P < 0.00005). The data indicate that elevated cord IgE as determined by PACIA is a good predictor of early-onset atopy, better than family history ( P < 0.008), and that primarily maternal atopy seems to affect fetal IgE synthesis.     

从HCV蛋白一级结构预测其C,E,NS5区的CD_4~ T细胞抗原位点

我们根据ＣＤ４＋Ｔ细胞识别抗原位点的物理化学和生物学特征，设计了一个具有查找两亲性螺旋状结构（ａｍｐｈｉｐａｔｈｉｃｈｅｌｉｘｓｔｒｕｃｔｕｒｅ）肽段功能的计算机程序。用该程序对ＨＣＶ－１型病毒Ｃ、Ｅ（Ｅ１、Ｅ２／ＮＳ１）、ＮＳ５蛋白一级结构进行分析，发现这些蛋白区存在ＣＤ４＋Ｔ细胞识别位点。此结果支持了ＣＤ４＋Ｔ细胞对ＨＣＶＣ，Ｅ，ＮＳ５区可发生增殖反应的结论。提示该程序可作为一种预测ＣＤ４＋Ｔ细胞识别ＨＣＶ抗原位点的方法。     

Analysis of mid-trimester corticotrophin-releasing hormone and alpha-fetoprotein concentrations for predicting pre-eclampsia

The aims of this study were firstly to examine if corticotrophin-releasing hormone (CRH) concentrations in maternal plasma were significantly elevated in Chinese pregnancies complicated by pre-eclampsia, secondly to assess if this elevation could be detected in the mid-trimester before onset of clinical signs of the disease, and thirdly to evaluate the performance of using maternal CRH and/or alpha-fetoprotein (AFP) concentrations in the mid-trimester for prediction of pre-eclampsia. The first part of this study was tested in a cohort of 39 subjects. The CRH concentrations were significantly elevated in pregnant women complicated by pre-eclampsia. The second and third parts of the study involved a different cohort of 1021 subjects. Both CRH and AFP concentrations in the mid-trimester were significantly elevated in those who subsequently developed pre-eclampsia. However, when used for prediction of pre-eclampsia, neither the CRH nor AFP concentrations alone in the mid-trimester had strong predictive value. Although the combination of both tests improved the detection rate compared to the use of CRH alone, the small increase in the likelihood ratio from 1.9 to 2.6 did not suggest that the combination would be of great clinical value.     

Abdominal lean muscle is associated with lower mortality among kidney waitlist candidates

Morphometric assessments, such as muscle density and body fat distribution, have emerged as strong predictors of cardiovascular risk and postoperative morbidity and mortality. To date, no study has examined morphometric mortality risk prediction among kidney transplant (KT) candidates. KT candidates, waitlisted 2008‐2009, were identified (n=96) and followed to the earliest of transplant, death, or administrative end of study. Morphometric measures, including abdominal adipose tissue, paraspinous and psoas muscle composition, and aortic calcification, were measured from CTs. Risk of waitlist mortality was examined using Cox proportional hazard regression. On adjusted analyses, radiologic measures remained independently and significantly associated with lower waitlist mortality; the addition of radiologic measures significantly improved model predictive ability over models containing traditional risk factors alone (net reclassification index: 0.56, 95% CI: 0.31‐0.75). Higher psoas muscle attenuation (indicative of leaner muscle) was associated with decreased risk of death (aHR: 0.93, 95% CI: 0.91‐0.96, P<.001), and for each unit increase in lean paraspinous volume, there was an associated 2% decreased risk for death (aHR: 0.98, 95% CI: 0.96‐0.99, P=.03). Radiologic measures of lean muscle mass, such as psoas muscle attenuation and paraspinous lean volume, may improve waitlist mortality risk prediction and candidate selection.     

降钙素原及C反应蛋白联合检测在急性重度胰腺炎发生风险中的预测价值

目的探讨早期降钙素原(PCT)及C反应蛋白(CRP)水平在急性重度胰腺炎发生风险中的预测价值。方法收集2013年1月至2015年12月在我院治疗的68例急性胰腺炎患者为研究对象进行回顾性研究。所有病例依照2013版中国急性胰腺炎诊疗指南将患者划分为轻度胰腺炎组(对照组),以及重度胰腺炎组(观察组)。通过t检验、Logistic回归以及ROC曲线分析起病24小时内的PCT及CRP水平与重度胰腺炎发生的相关性。结果观察组中PCT、CRP平均水平高于对照组(P0.001),Logistic回归分析得到PCT、CRP的OR值分别为1.41、1.125,两者95%置信区间均1,PCT、CRP均为重度胰腺炎的危险因素,可联合对重度胰腺炎发生风险进行预测。而ROC曲线提示PCT对重度胰腺炎预测敏感性及准确性要优于CRP。结论通过早期检测血清PCT和CRP水平能够对急性胰腺炎患者的病情严重程度提供帮助,而对重度胰腺炎早期综合治疗具有一定的临床指导价值。