Caspase-3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias

AIMS: Apoptosis is mediated by apoptosis-specific genes, certain oncogenes and tumour suppressor genes. Caspase-3, a group of cystein proteases, is involved in the induction of apoptosis and has been considered to correlate with apoptosis. The aim of this study was to determine whether caspase-3 is expressed in prostatic carcinoma and benign prostatic hyperplasia, and correlated with the apoptosis. METHODS AND RESULTS: We studied the apoptotic index and caspase-3 immunoreactivity in 40 cases of benign nodular hyperplasia (BPH) and 40 cases of prostate carcinoma (PCA) by in-situ labelling and immunohistochemistry. The mean number of apoptotic bodies in cases with BPH was not significantly different from cases with PCA I (Gleason score 2-4), but samples from patients with PCA II (Gleason score 5-7) and PCA III (Gleason score 8-10) showed a significantly higher apoptotic number than cases with BPH. Positive staining for caspase-3 was seen in 42.5% (17/40) of the BPH, and 27.5% (11/40) of the PCA: PCA I was 41.7% (5/12), PCA II 14.3% (2/14) and PCA III was 28.6% (4/14). CONCLUSIONS: Based on our results, the number of apoptotic bodies was not correlated with the caspase-3 expression and there was no relationship between caspase-3 expression and Gleason score. However, the number of apoptotic bodies was significantly higher in cases with intermediate (Gleason score 5-7) and high-grade (Gleason score 8-10) PCAs than cases with BPH and low-grade PCAs (Gleason score 2-4).     

The atopy patch test -- reproducibility and comparison of different evaluation methods

BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.     

急性胰腺炎患者空腹高血糖发生率及其危险因素分析

目的:回顾性分析急性胰腺炎(AP)患者空腹高血糖发生率及其危险因素。方法:收集2018-01—2018-12武汉大学人民医院胰腺外科133例AP且无糖尿病(DM)病史的住院患者病历资料,按照不同性别、年龄、AP临床分型、病因、CT指数评分(CISI)等分组,χ2检验分析各组临床因素与空腹高血糖(FPG≥6.1mmol/L)发生率的关系,多因素二元logistic回归分析空腹高血糖独立危险因素。结果:AP临床分型(χ2=5.494,P=0.019)和CTSI(χ2=6.236,P=0.013)与AP患者空腹高血糖相关(P<0.05)。CTSI≥6分(P=0.015,OR=2.920,95%Cl=1.234—6.905)为AP患者空腹高血糖的独立危险因素(P<0.05)。结论:临床分型中重症+重症及CTSI≥6分的AP患者易发生空腹高血糖,尤其CTSI≥6分是AP后空腹高血糖的独立危险因素,临床应高度关注。     

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.     

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.     

A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree

 Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and 17 related genes for autosomal dominant nonsyndromic hearing loss have been identified. In a Chinese pedigree characterized by autosomal dominant inheritance with bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment, the putative disease gene locus was localized to chromosome 5q31.1-32 by a genome-wide scan. Fine mapping indicated that the disease gene was located within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum two-point logarithm of differences (LOD) score of 6.89 (θ = 0) at D5S2017. By the candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at 5q31 was performed. No mutation was found, suggesting that this is a novel deafness locus, which has been named DFNA42. Received: May 8, 2002 / Accepted: October 1, 2002     

Comparison of the PROMIS Preference Score (PROPr) and EQ-5D-5L Index Value in General Population Samples in the United Kingdom,France, and Germany

ObjectivesThe Patient-Reported Outcome Measurement Information System (PROMIS) Preference score (PROPr) can be used to assess health state utility (HSU) and estimate quality-adjusted life-years in cost-effectiveness analyses. It is based on item response theory and promises to overcome limitations of existing HSU scores such as ceiling effects. The PROPr contains 7 PROMIS domains: cognitive abilities, depression, fatigue, pain, physical function, sleep disturbance, and ability to participate in social roles and activities. We aimed to compare the PROPr with the 5-level EQ-5D (EQ-5D-5L) in terms of psychometric properties using data from 3 countries.MethodsWe collected PROMIS-29 profile and EQ-5D-5L data from 3 general population samples (United Kingdom = 1509, France = 1501, Germany = 1502). Given that cognition is not assessed by the PROMIS-29, it was predicted by the recommended linear regression model. We compared the convergent validity, known-groups construct validity, and ceiling and floor effects of the PROPr and EQ-5D-5L.ResultsThe mean PROPr (0.48, 0.53, 0.48; P<.01) and EQ-5D-5L scores (0.82, 0.85, 0.83; P<.01) showed significant differences of similar magnitudes (d = 0.34; d = 0.32; d = 0.35; P<.01) across all samples. The differences were invariant to sex, income, occupation, education, and most conditions but not for age. The Pearson correlation coefficients between both scores were r = 0.74, r = 0.69, and r = 0.72. PROPr’s ceiling and floor effects both were minor to moderate. The EQ-5D-5L’s ceiling (floor) effects were major (negligible).ConclusionsBoth the EQ-5D-5L and the PROPr assessed by the PROMIS-29 show high validity. The PROPr yields considerably lower HSU values than the EQ-5D-5L. Consequences for quality-adjusted life-year measurements should be investigated in future research.     

中医药随机对照试验中采用真实世界数据作为对照组的研究设计及挑战

在设计随机对照试验（RCT）时,如果对照组存在患者招募和入组困难的情况,就会影响试验整体实施。近年来,真实世界数据（RWD）作为除RCT之外的数据来源,在医疗领域中发挥着越来越重要的作用。中医药RCT中可以尝试采用将RWD作为对照组的研究设计,不仅可以有效解决中医药RCT西医对照组患者入组困难的问题,同时能提供有力证据来评价中医药的疗效。倾向评分法目前已广泛应用于真实世界研究中混杂因素的处理,该文对RCT采用RWD作为对照组的这类设计中,基于倾向评分法常见的4种研究设计形式以实例分别进行了介绍,包括不对称随机分配、基于倾向评分分层法的两阶段设计、倾向评分联合复合似然法及倾向评分多种方法的联合。同时,这种设计类型也存在着方法学的挑战,包括RWD数据源必须是高质量且关键信息需要规范收集、RCT和RWD患者基线特征应该具有可比性、协变量选择时需要把所有已知与干预措施和结局相关的协变量都纳入进行分析等。在中医药领域采用这种设计时,还存在着有些RWD中医证型信息缺失、中医结局指标缺失等问题,在使用RWD时,需要根据数据实际情况决定如何分析。该文对以RWD作为RCT对照组的设计类型及面临的方法学挑战进行了介绍,期望能为研究者今后使用这类设计提供方法学借鉴。     

Associations of Dietary Patterns with Incident Depression: The Maastricht Study

Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.     

Dietary Habit Is Associated with Depression and Intelligence: An Observational and Genome-Wide Environmental Interaction Analysis in the UK Biobank Cohort

Dietary habits have considerable impact on brain development and mental health. Despite long-standing interest in the association of dietary habits with mental health, few population-based studies of dietary habits have assessed depression and fluid intelligence. Our aim is to investigate the association of dietary habits with depression and fluid intelligence. In total, 814 independent loci were utilized to calculate the individual polygenic risk score (PRS) for 143 dietary habit-related traits. The individual genotype data were obtained from the UK Biobank cohort. Regression analyses were then conducted to evaluate the association of dietary habits with depression and fluid intelligence, respectively. PLINK 2.0 was utilized to detect the single nucleotide polymorphism (SNP) × dietary habit interaction effect on the risks of depression and fluid intelligence. We detected 22 common dietary habit-related traits shared by depression and fluid intelligence, such as red wine glasses per month, and overall alcohol intake. For interaction analysis, we detected that OLFM1 interacted with champagne/white wine in depression, while SYNPO2 interacted with coffee type in fluid intelligence. Our study results provide novel useful information for understanding how eating habits affect the fluid intelligence and depression.