In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography

Background

In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity.

Associations between genetic risk,functional brain network organization and neuroticism

Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.     

Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D‐negative pregnant women

To guide anti‐D prophylaxis, Dutch D‐ pregnant women are offered a quantitative fetal‐RHD‐genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D‐ pregnant women. A variant allele is present in at least 0·96% of Dutch D‐ pregnant women The D‐ serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors. 43 different RHD variant alleles were detected, including 15 novel alleles (11 null‐, 2 partial D‐ and 2 DEL‐alleles). Of those novel null alleles, one allele contained a single missense mutation (RHD*443C>G) and one allele had a single amino acid deletion (RHD*424_426del). The D‐ phenotype was confirmed by transduction of human D‐ erythroblasts, consolidating that, for the first time, a single amino acid change or deletion causes the D‐ phenotype. Transduction also confirmed the phenotypes for the two new variant DEL‐alleles (RHD*721A>C and RHD*884T>C) and the novel partial RHD*492C>A allele. Notably, in three additional cases the DEL phenotype was observed but sequencing of the coding sequence, flanking introns and promoter region revealed an apparently wild‐type RHD allele without mutations.     

Targeting exocytosis: ins and outs of the modulation of quantal dopamine release

Dopaminergic neurotransmission is mediated by the vesicular release of dopamine (DA), i.e. DA exocytosis. DA exocytosis and its modulation are generally believed to affect neuronal communication, development, maintenance and survival, and contribute to extracellular DA levels in the brain. As a result, DA exocytosis likely plays an important role in several neurological and psychiatric disorders, like Parkinson's disease (PD) and schizophrenia. As exocytosis is part of a sophisticated ensemble of processes, it can be modulated at different levels, including DA synthesis, uptake and vesicular transport as well as Ca(2+)-homeostasis and exocytotic proteins. Nonetheless, to be effective, modulation of exocytosis should result in functional changes, which are reflected by changes in release frequency, vesicle contents, and the time course of the exocytotic event. As will be shown in this review, functional changes in DA exocytosis can be produced by e.g. pharmacological/drug treatment, feedback mechanisms and up/down-regulation of exocytosis-related proteins. Moreover, the mode of DA exocytosis, i.e. classical full fusion or kiss-and-run exocytosis, could also serve as a potential target for functional modulation of dopaminergic neurotransmission. Since the onset and progression of neurological and psychiatric disorders often show a strong correlation with changes in brain DA levels, DA synthesis, transport or uptake, the findings described in this review highlight the importance of the modulation of (the mode of) DA exocytosis for normal progression of dopaminergic neurotransmission and the potential of exocytotic processes as drug targets.     

A Mixed Method Study Investigating the Impact of Talking about Patients’ Internet Use on Patient-Reported Outcomes

This study aims to propose and test a model that provides a more comprehensive understanding of the impact of discussing online health information on patient outcomes. By combining survey data (N = 160) and qualitative analysis of video recordings of consultations (N = 165) with structural equation modeling, this study explores: (1) whether patients and health-care providers talk about online medical information and (2) the impact of talking about online medical information on patient outcomes (patient satisfaction, recall of medical information, and medication adherence). Results show that more than half of the patients searched online prior to their consultation. In about half of these consultations (46.81%), the online information was discussed. Patients were more satisfied with the consultation if the online information was discussed during the consultation. Moreover, patient satisfaction was positively related to recall of medical information, but only in patients with whom the online information was discussed. There was no effect found on medication adherence. Results of this study demonstrate the importance of talking about online information during a consultation for improving patient outcomes. Implications for research are discussed.     

EGFR mutation analysis in sputum of lung cancer patients: A multitechnique study

Objectives

Epidermal growth factor receptor (EGFR) mutations have been identified in lung adenocarcinomas and are associated with high response chance to EGFR tyrosine kinase inhibitors. EGFR mutations can be detected in tumour tissue, cytology specimens and blood from lung cancer patients. Thus far, EGFR mutation analysis has not been systematically demonstrated for sputum samples. The aim of the present study was to determine whether EGFR mutation analysis is attainable on sputum samples, employing different assays in a multicenter study.

Materials and methods

Sputum DNA from 10 lung cancer patients with confirmed EGFR mutation in their tumour tissue, 10 lung cancer patients without evidence of an EGFR mutation, and 10 patients with chronic obstructive pulmonary disease (COPD) was used for mutation analysis by Cycleave PCR, COLD-PCR, PangaeaBiotech SL Technology (PST), and High Resolution Melting, respectively. Targeted resequencing (TruSeq Amplicon Cancer Panel) and droplet digital PCR were additionally performed on the 10 samples with EGFR mutation.

Results

Dependent on the assay, EGFR mutations could be detected in 30–50% of the sputum samples of patients with EGFR mutations. The different techniques revealed consistent results, with slightly higher sensitivity for PST. Neither the lung cancer patients without EGFR mutation nor the COPD controls tested positive for EGFR mutations in their sputum samples, indicating high clinical specificity of all assays.

Conclusion

EGFR mutations can be detected in sputum samples from patients with EGFR-mutated non-small cell lung cancer, which may replace biopsy procedure for some patients.     

The Code of Practice and its enduring relevance in Europe and Eastern and Southern Africa

Background

The relevance and effectiveness of the WHO Global Code of Practice on the International Recruitment of Personnel will be reviewed by the World Health Assembly in 2015. The origins of the Code of Practice and the global health diplomacy process before and after its adoption are analyzed herein.

Methods and Results

Case studies from the European and eastern and southern African regions describe in detail successes and failures of the policy implementation of the Code. In Europe, the Code is effective and even more relevant than before, but might require some tweaking. In Eastern and Southern Africa, the code is relevant but far from efficient in mitigating the negative effects of health workforce migration.

Conclusions

Solutions to strengthen the Code include clarification of some of its definitions and articles, inclusion of a governance structure and asustainable and binding financing system to reimburse countries for health workforce losses due to migration, and featuring of health worker migration on global policy agendas across a range of institutional policy domains.

     

Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group

This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51–3.5) and 2.3 (95 % CI 1.72–5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment.     

Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes

This study was undertaken to examine the role fibroblasts play in the formation of the basement membrane (BM) in human skin equivalents. For this purpose, keratinocytes were seeded on top of fibroblast-free or fibroblast-populated collagen matrix or de-epidermized dermis and cultured in the absence of serum and exogenous growth factors. The expression of various BM components was analyzed on the protein and mRNA level. Irrespective of the presence or absence of fibroblasts, keratin 14, hemidesmosomal proteins plectin, BP230 and BP180, and integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta4 were expressed but laminin 1 was absent. Only in the presence of fibroblasts or of various growth factors, laminin 5 and laminin 10/11, nidogen, uncein, type IV and type VII collagen were decorating the dermal/epidermal junction. These findings indicate that the attachment of basal keratinocytes to the dermal matrix is most likely mediated by integrins alpha1beta1 and alpha2beta1, and not by laminins that bind to integrin alpha6beta4 and that the epithelial-mesenchymal cross-talk plays an important role in synthesis and deposition of various BM components.