The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection

The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP’s association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP’s clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.     

Integrated quality assessment for diabetes care in Portuguese primary health care using prevention quality indicators

AimsThis study evaluates the prevention quality indicators (PQI) for Diabetes Mellitus (DM) in Portugal using contemporary data and explores their variability according to Primary Health Care (PHC) quality indicators.MethodsWe conducted a retrospective observational analysis of secondary data comprising Portuguese PHC indicators by health centres group (ACES) and the National Hospital Morbidity Database. We calculated and analysed age-sex-adjusted rates for each PQI. Worse-performing ACES were identified using the 2017 median PQI values as an assessment cut-off. A multivariate logistic analysis was carried to find variables associated with the likelihood of being a worse-performing ACES for the biennium.ResultsThe median values of the indicator PQI93 - Prevention Quality Diabetes Composite were 79 and 65.2 hospitalizations per 100 000 pop, in 2016 and 2017 respectively. Diabetes long term complications (PQI 03) accounted for most of the hospitalizations. The quality indicator in PHC with greater influence on PQI93 was the proportion of DM patients with <65 years with test results for HbA1c < = 6.5%.ConclusionsThis study shows that some PHC quality indicators are closely related to DM care, and so their monitoring is of high importance. Diabetes long term complications (PQI 03) demand greater attention from PHC professionals.     

ESPR uroradiology task force imaging recommendations in paediatric uroradiology,part VII: standardised terminology,impact of existing recommendations,and update on contrast-enhanced ultrasound of the paediatric urogenital tract

Our purpose is to harmonise and standardise terminology in paediatric uroradiology, to provide and update recommendations for contrast-enhanced US to standardise imaging and encourage further research, and to assess the impact of the existing recommendations in paediatric urogenital imaging. Based on thorough review of literature and variable practice at several centres and after discussion within urogenital imaging groups as well as with other subspecialties, we propose a standardisation of terminology in urogenital imaging. An update with recommendations on paediatric contrast-enhanced US has been issued based on available literature and reports. Finally, a questionnaire has been used to assess the knowledge, applicability and usefulness of, and the adherence to existing recommendations of the European Society of Paediatric Radiology (ESPR) Uroradiology Task Force. In conclusion, the ESPR is working to improve patient safety and optimise paediatric urogenital imaging. Standardisation of terminology and provision of updated knowledge on contrast-enhanced US in childhood will contribute to this task, ideally reducing the need for invasive or radiating imaging. Not all existing recommendations are commonly known, which limits adherence to these recommendations and the availability of comparable data and evidence for future adaptation of imaging strategies in paediatric uroradiology.     

Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in µm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm³, MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.     

Polypyrrole increases branching and neurite extension by Neuro2A cells on PBAT ultrathin fibers

We present a methodology for production and application of electrospun hybrid materials containing commercial polyester (poly (butylene adipate-co-terephthalate; PBAT), and a conductive polymer (polypyrrole; PPy) as scaffold for neuronal growth and differentiation. The physical–chemical properties of the scaffolds and optimization of the electrospinning parameters are presented. The electrospun scaffolds are biocompatible and allow proper adhesion and spread of mesenchymal stem cells (MSCs). Fibers produced with PBAT with or without PPy were used as scaffold for Neuro2a mouse neuroblastoma cells adhesion and differentiation. Neuro2a adhered to PBAT and PBAT/PPy2% scaffolds without laminin coating. However, Neuro2a failed to differentiate in PBAT when stimulated by treatment with retinoic acid (RA), but differentiated in PBAT/PPy2% fibers. We hypothesize that PBAT hydrophobicity inhibited proper spreading and further differentiation, and inhibition was overcome by coating the PBAT fibers with laminin. We conclude that fibers produced with the combination of PBAT and PPy can support neuronal differentiation.     

Expression and localization of Aquaporin 3 (AQP3) in folliculogenesis of ewes

The mRNA expression and localization of Aquaporin 3 (AQP3) were investigated in the ovarian follicles of ewes at different stages of development (primordial, primary, secondary, small, and large antral). The gene expression was quantified by qPCR, while the protein identification and localization were determined by Western blot and immunohistochemistry, respectively. Analysis revealed that AQP3 mRNA was detected only in the antral follicles, whereas the protein expression was detected in the oocyte and granulosa cells in all stages of follicular development. The latter observation suggests that the presence of AQP3 in follicles of all categories, especially in the antral follicles, provides novel insights on the mechanisms that regulate the flow of water between cells during the formation of antral follicles in sheep.