Induction and Analysis of Epithelial to Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) is essential for proper morphogenesis during development. Misregulation of this process has been implicated as a key event in fibrosis and the progression of carcinomas to a metastatic state. Understanding the processes that underlie EMT is imperative for the early diagnosis and clinical control of these disease states. Reliable induction of EMT in vitro is a useful tool for drug discovery as well as to identify common gene expression signatures for diagnostic purposes. Here we demonstrate a straightforward method for the induction of EMT in a variety of cell types. Methods for the analysis of cells pre- and post-EMT induction by immunocytochemistry are also included. Additionally, we demonstrate the effectiveness of this method through antibody-based array analysis and migration/invasion assays.     

Patients with heart failure with preserved ejection fraction and low levels of natriuretic peptides

Aims

Heart failure with preserved ejection fraction (HFpEF) is common and its management remains difficult. B-type natriuretic peptide (BNP) levels are used to diagnose heart failure, and as an entry criterion for inclusion into trials. We investigated a population of HFpEF patients who had been randomised into a study based on clinical parameters, and compared those with low BNP levels to those with elevated BNP levels.

Methods

We examined patients who had been enrolled in the Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure (COACH), with preserved left ventricular ejection fraction (LVEF ≥ 40 %), and compared those with low BNP (< 100 pg/ml; n = 30) to those with elevated BNP (≥ 100 pg/ml; n = 127). Baseline characteristics, comorbidities, biomarkers, quality of life, and outcome parameters (hospitalisations and death) were compared between the groups. To validate our findings, we repeated all analyses for NT-proBNP (< 300 pg/ml and ≥ 300 pg/ml).

Results

Patients were similar with regard to most clinical characteristics (including age, sex, and LVEF), biomarkers, and comorbidities. In contrast, patients with a low BNP had higher body mass index levels (31 kg/m² vs. 27 kg/m²; p < 0.01) and lower cardiac troponin I (9 pg/ml vs. 15 pg/ml; p = 0.02). In addition, these patients were less frequently prescribed diuretics and beta-blockers. No differences in quality of life, heart failure related symptoms and the primary and secondary outcomes were observed between these groups. These observations were confirmed for NT-proBNP.

Conclusion

Among the patients with clinically diagnosed HFpEF, those with low BNP are strikingly similar to those with elevated BNP levels, except for BMI, which was significantly higher in these patients.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-016-0816-8) contains supplementary material, which is available to authorized users.     

自拟柴芍护膜汤联合莫沙必利治疗反流性食管炎的临床效果观察

目的:研究自拟柴芍护膜汤联合莫沙必利治疗反流性食管炎的临床效果和可能机制。方法:选择2015年12月～2018年12月我院内科杂病门诊治疗的70例反流性食管炎患者,将其随机分为两组。对照组服用莫沙必利,每次5 mg,每天3次;观察组联合服用自拟柴芍护膜汤以及莫沙必利。比较两组患者治疗后的临床治疗效果,治疗前后泛酸、烧心、脘腹胀满、嗳气、呃逆、情志抑郁、善太息、食欲不振以及嘈杂等症状的严重程度、血浆胃动素和血清胃泌素水平的变化。结果:治疗后,观察组的有效率为91.43%,明显高于对照组(71.43%,P0.05)。两组治疗后的泛酸、烧心、脘腹胀满、嗳气、呃逆、情志抑郁、善太息、食欲不振以及嘈杂评分均较治疗前明显降低(P0.05),且观察组的上述症状评分明显低于对照组(P0.05);两组治疗后的血浆胃动素和血清胃泌素水平均较治疗前明显升高(P0.05),且观察组以上指标均明显高于对照组(P0.05)。结论:自拟柴芍护膜汤联合莫沙必利能有效改善反流性食管炎的临床症状,其作用机制可能与提高血浆胃动素和血清胃泌素水平有关。     

Evaluation of leaf features in forest trees: Methods,techniques, obtainable information and limits

Tree leaves are interfaces between the whole organism and the environment. Leaves display a series of attributes that are linked to specific functions (functional leaf traits—FLT) and/or show responses to biotic and abiotic stress factors (stress response traits, SRT), which can be subdivided into: (a) morphological traits; (b) chemical traits; (c) physiological traits; (d) symptoms. The analysis of FLT is a useful tool for tree species and provenance phenotyping, due to the adaptation of trees to environmental stress. Additionally, FLT can be used as response factor in long term and large spatial scales surveys of forest conditions. Despite these potential benefits of leaf traits in the assessment of ecosystem health and functioning, leaf sampling in forests is time-consuming and costly, especially in forests with a complex vertical and horizontal structure and in remote forest areas. Once a foliar sample has been collected, many different analyses can be carried out; however, analyses should be technically simple and able to be performed within one day following the leaf collection (i.e., on fresh samples), or after air-drying the leaves themselves (analysis of dried specimens). This paper reports the results of leaf sampling and foliar analyses carried out in previous research projects and revises the current state-of-the-art. The leaf traits that are easily obtainable from leaf sampling are listed, together with the operational procedures necessary for their measurement, described in a standardized protocol. Their ecological and functional relevance is discussed in relation to their potential information (as indicators of climatic stress, drought, air and soil pollution, tree light-use and competition, plant nutritional status, health and general plant stress conditions). Finally, this review provides suggestions for the elaboration and reporting of data, and proposes some guidelines to improve the effectiveness of foliar analysis in the assessment of forest ecosystem health, properties and functioning.     

Exploration of the possible effect on survival of lead-time associated with implementation of cancer patient pathways among symptomatic first-time cancer patients in Denmark

BackgroundImplementation of standardised cancer patient pathways (CPPs) has provided faster diagnosis of cancer. Cancer survival has improved during the same time period. Concern has been raised that the faster diagnosis may have introduced lead-time bias by elongating the period from diagnosis to death.AimWe aimed to analyse the possible effect of lead time on survival due to expedited cancer diagnosis after the implementation of national CPPs among incident cancer patients diagnosed through Danish primary care.Material and methodsWe used actual observed differences in diagnostic intervals to estimate the lead-time effect. We used data from sub-cohorts from the Danish Cancer in Primary Care (CaP) cohort of first-time cancer patients: before and after CPP implementation. To calculate differences in absolute survival, we estimated the survival function after advancing the date of diagnosis in the before cohort to an earlier point in time and hereby adjusting for lead time for nine cancer types and all combined by using Kaplan-Meier analysis.ResultsAdvancing the date of diagnosis implied that the absolute one-year survival increased from 68.5% to 69.4%. This accounted for 13% of the observed differences in absolute one-year survival from before to after CPPs.ConclusionThe lead time caused by shorter diagnostic intervals after implementation of Cancer Patient Pathways seems to explain less than 15% of the observed changes in the one-year survival estimates for cancer patients in Denmark.     

Genetic and epigenetic factors associated with depression: An updated overview

Depression is a complex psychiatric disturbance involving many environmental, genetic, and epigenetic factors. Until now, genetic, and non-genetic studies are still on the way to understanding the complex mechanism of this disease, and there are still many questions that have not yet been answered. Depression includes a large spectrum of heterogeneous symptoms correlated to the deficit of a range of psychological, cognitive, and emotional processes, and it affects various age groups. It is classified into several types according to the severity of symptoms, time of occurrence, and time. Following the World Health Organization (WHO), depression attacks near 350 million persons globally. Several factors overlap in causing depression, including genetic and epigenetic factors, environmental conditions, various stresses, lack of some nutrients to which people are exposed, and excessive stress and abuse in childhood. This study included conducting surveys on depression and new treatment trends based on epigenetic factors associated with the occurrence of the disease. Epigenetic factors provide a completely novel dimension to therapeutic approaches as most diseases are not monogenic, and it is likely that the environment has a significant contribution. Epigenetic inheritance is included in many mental and psychiatric disorders such as depression. In general, epigenetic modifications could be summarized in 3 major points: DNA methylation, histone modification, and non-mediated regulation of RNA (ncRNA). This study also describes some genes associated with one of the depressive disorders using bioinformatics tools and gene bank and had the genes: SLC6A4, COMT, TPH2, FKBP5, MDD1, HTR2A, and MDD2. As in this study, the awareness of Saudi society about depression and its genetic and non-genetic causes was estimated. The results showed that an encouraging percentage of more than half of the research sample possessed correct information about this disorder.     

Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month,multicentre, randomised studies (ACLIFORM and AUGMENT)

Background

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta₂-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).

Methods

Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV₁]/forced vital capacity <70 % and FEV₁ ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.

Results

The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).

Conclusions

Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT01462942","term_id":"NCT01462942"}}NCT01462942 and {"type":"clinical-trial","attrs":{"text":"NCT01437397","term_id":"NCT01437397"}}NCT01437397 (ClinicalTrials.gov)

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.     

论股骨头坏死误诊的现状及分析

股骨头坏死是一种常见的疾病,在30岁至60岁年龄段的人群中较为常见,临床的症状包括疼痛以及髋部不适等,股骨头坏死在早期很难发现,由于没有得到准确的诊断,耽误了最佳的治疗时间和有效的治疗,随着病情的发展,最终将会造成股骨头变形以及塌陷,从而引起骨性关节炎,对髋关节功能的影响是很大的,甚至会丧失髋关节的基本功能。股骨头坏死的病状体征和早期症状存在一定的隐蔽性,因此,造成误诊的情况频繁发生。此外,有些疾病的症状表现为髋关节疼痛,最后反而容易被误诊为股骨头坏死。     

COPD and disease-specific health status in a working population

Background

It has been debated whether treatment should be started early in subjects with mild to moderate COPD. An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD.

Purpose

To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation.

Methods

A total of 1333 healthy industrial workers aged ≥40 years performed spirometry and completed the St. George’s Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT).

Results

The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%. All SGRQ and CAT scores were skewed to the milder end. In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8. In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects. Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero. The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero). Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects.

Conclusion

The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD. All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups. This suggests that symptom-based methods are not suitable screening tools in a healthy general population.     

Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty

A simple, validated protocol consisting of a battery of tests is available to identify elderly patients with frailty syndrome. This syndrome of decreased reserve and resistance to stressors increases in incidence with increasing age. In the elderly, frailty may pursue a step-wise loss of function from non-frail to pre-frail to frail. We studied frailty in HIV-infected patients and found that ~20% are frail using the Fried phenotype using stringent criteria developed for the elderly^1,2. In HIV infection the syndrome occurs at a younger age.HIV patients were checked for 1) unintentional weight loss; 2) slowness as determined by walking speed; 3) weakness as measured by a grip dynamometer; 4) exhaustion by responses to a depression scale; and 5) low physical activity was determined by assessing kilocalories expended in a week''s time. Pre-frailty was present with any two of five criteria and frailty was present if any three of the five criteria were abnormal.The tests take approximately 10-15 min to complete and they can be performed by medical assistants during routine clinic visits. Test results are scored by referring to standard tables. Understanding which of the five components contribute to frailty in an individual patient can allow the clinician to address relevant underlying problems, many of which are not evident in routine HIV clinic visits.