Quality of life and rural place of residence in Polish women : population based study

Objective: The purpose of this population-based study was to analyse the association between the health-related quality of life and rural residence among Polish females, including variables related to social environment and clinical characteristics. Methods: The snowball recruitment method was used to invite 1,560 women aged 45-60 to participate in the study. Participants received a questionnaire about demographic characteristics, environmental and work stress, use of anxiolytichypnotic medications and self-reported quality of life based on the SF-36 form. Univariate and multivariate analysis was carried out by means of a logistic regression model. Results: We found worse physical health and better mental health among women living in rural areas compared to those from urban settings. The rural residence was an independent predictor for poor physical health (below 25 percentile) odds ratio [OR] 1.6 95%, confi dence interval [CI] 1.17-2.2). Living in rural areas was also associated at the borderline level of statistical signifi cance, with reduction of risk of low quality of life in mental health (OR = 0.75; 95% CI = 0.55-1.02). According to other results from multivariate analysis, being retired, receiving social pension, long duration of illness symptoms, and consulting a medical specialist were the risk factors of reported bad physical health. Higher education and access to medical specialist protects against having a bad quality of life related to mental health. Being given the sack, stress at work, feeling anger, and long duration of symptoms are the risk factors of poor mental health. Conclusion: The rural residence is strongly associated with environmental and psychosocial factors in women aged 40-65

Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity

It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS-induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras-induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation-induced inactivation. Along those lines, Prdx1 tumour suppression of Ras- or ErbB-2-induced transformation was mediated mainly via PTEN

INTERNET SEARCHES FOR “SUICIDE”, ITS ASSOCIATION WITH EPIDEMIOLOGICAL DATA AND INSIGHTS FOR PREVENTION PROGRAMS

Background: Literature demonstrates that analysis of internet search data is a useful tool in predicting the occurrence of illnesses and health-related behaviors. The aim of the study was to quantitatively present the trends in Google searches for the keyword “suicide” and to analyze its correlation with the number of suicides in Poland. Subjects and methods: We used the Google Trends tool to compile data for years 2004-2016. Statistical analysis was performed for annual, monthly, daily and hourly data. Official data on suicide in Poland were obtained from the Central Statistical Office and the General Police Headquarters of Poland. Results: A gradual decrease in Google Relative Search Volume of the keyword “suicide” was observed in years 2004-2014, despite the significant increase of suicide rate in Poland (R=-0.24). Reverse correlation was also found between regional suicide coefficients and search volume (R=-0.22). The highest search volumes were recorded in winter months, first days of the week and at night hours (p<0.001). Conclusions: Presented results may contribute to more effective suicide prevention programs. By specifying the time intervals in which searching suicide information is the highest, it will become easier get to individuals at risk

Caracterización petrológica y geoquímica del moteado leucocrático en rocas basálticas alcalinas.

La presencia de un moteado leucocrático en basaltos alcalinos es un aspecto bastante frecuente en este tipo de lavas. A pesar de ello los estudios sobre su origen e implicaciones son hoy en día escasos y controvertidos. Es por ello que en el presente trabajo se presenta un estudio detallado del moteado en el que se incluyen relaciones de campo así como una caracterización textural, mineralógica y geoquímica de una selección de muestras. Los resultados obtenidos permiten sugerir que el moteado leucocrático se desarrolla como consecuencia del remplazamiento postmagmático de leucita primaria intersticial, dispuesta en forma de cuerpos poiquilíticos, por analcima secundaria. El aumento de volumen que supone este remplazamiento explica el mayor grado de fracturación de los minerales esenciales (olivino, clinopiroxeno y plagioclasa) así como la formación de grietas capilares que se disponen de forma radial desde los motes y que pueden llegar a comprometer la coherencia de la roca. Las observaciones realizadas indican que el desarrollo y tipología de moteado están fuertemente condicionados por la temperatura de la roca y la presencia de agua. Palabras clave: moteado leucocrático, basaltos alcalinos, analcimitización, leucita poiquilítica intersticial. /// The presence of sunburns is a common feature in alkaline basaltic rocks. Despite their frequent occurrence, works that have studied the origin and implications of sunburn presence are still scarce and controversial. In this study we present a detailed work on sunburns including field relations and a textural, mineralogical and geochemical characterization of a set of selected samples. The obtained results evidence that leucocratic discolorations are developed as a consequence of post-magmatic replacement of primary interstitial groundmass leucite arranged in poikilitic bodies by secondary analcime. The volume increase associated to this replacement explains the major degree of fracturing of the framework minerals (olivine, clinopyroxene and plagioclase) as well as the development of radial capillary cracks that radiate outwards from the sunburns. Both characteristics can compromise the coherence of the rock. Al the observations indicate that the combination of rock temperature and water supply strongly conditions de development and type of sunburns

Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma

Burkitt lymphoma is a fast-growing tumor derived from germinal center B cells. It is mainly treated with aggressive chemotherapy, therefore novel therapeutic approaches are needed due to treatment toxicity and developing resistance. Disturbance of red-ox homeostasis has recently emerged as an efficient antitumor strategy. Peroxiredoxins (PRDXs) are thioredoxin-family antioxidant enzymes that scavenge cellular peroxides and contribute to red-ox homeostasis. PRDXs are robustly expressed in various malignancies and critically involved in cell proliferation, differentiation and apoptosis. To elucidate potential role of PRDXs in lymphoma, we studied their expression level in B cell-derived primary lymphoma cells as well as in cell lines. We found that PRDX1 and PRDX2 are upregulated in tumor B cells as compared with normal counterparts. Concomitant knockdown of PRDX1 and PRDX2 significantly attenuated the growth rate of lymphoma cells. Furthermore, in human Burkitt lymphoma cell lines, we isolated dimeric 2-cysteine peroxiredoxins as targets for SK053, a novel thiol-specific small-molecule peptidomimetic with antitumor activity. We observed that treatment of lymphoma cells with SK053 triggers formation of covalent PRDX dimers, accumulation of intracellular reactive oxygen species, phosphorylation of ERK1/2 and AKT and leads to cell cycle arrest and apoptosis. Based on site-directed mutagenesis and modeling studies, we propose a mechanism of SK053-mediated PRDX crosslinking, involving double thioalkylation of active site cysteine residues. Altogether, our results suggest that peroxiredoxins are novel therapeutic targets in Burkitt lymphoma and provide the basis for new approaches to the treatment of this disease

URINARY PROTEOMIC MARKERS OF IGA NEPHROPATHY, LUPUS NEPHRITIS AND MEMBRANOUS NEPHROPATHY

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide public health problem, related to increased morbidity and mortality. Glomerulopathies represent major causes of CKD and require complicated diagnostics. Standard of care includes kidney biopsy in order to confirm the type of nephropathy. However, biopsy brings specific risks. Therefore, non-invasive diagnostic and prognostic methods are sought. Urinary proteomics emerged as safe and promising tool, but still requires development and improvements. Our previous studies which are part of European Patent Application from 10th June 2016 (WO/2017/212463), identified urinary markers of IgA nephropathy. They included among others: alpha-1B-glycoprotein (A1BG), alpha-l-acid glycoprotein 1 (ORM-1), ferritin light chain (FTL) and serotransferrin (TF). The aim of this study was to evaluate them in comparison to patients with glomerulopathies of different etiologies, such as lupus nephritis (LN) and membranous nephropathy (MN). METHODS: This proteomic study included patients with CKD (41 IgAN, 33 LN, 26 MN, 6 with erytrocyturia of unknown etiology) and 19 healthy controls. Urine samples were obtained from a midstream of the: first-morning (FM) and second- or third-morning (SPOT) sample. The SPOT samples were processed up to 2 h and FM samples up to 4 h after collection, by agitating and gently inverting 4-6 times, portioned into 2-ml aliquots and stored at -80°C for further measurements. Western Blotting was used for analysis of the SPOT and FM samples, ELISA and mass spectrometry for SPOT urine only. The results were related to demographic data, standard laboratory tests and GFR estimated with use of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The urinary concentrations of A1BG, ORM-1, FTL and TF were found to be higher in CKD patients than in healthy controls. Moreover, these proteins varied depending on the disease. According to ELISA measurements, patients with IgAN, erytrocyturia and LN had significantly more A1BG and ORM-1 (p < 0.05), whereas TF was more elevated in LN and MN individuals comparing to healthy controls. The western blot analysis revealed significantly elevated level of A1BG, ORM-1 and FTL in IgAN, LN and MN, comparing to healthy control. Additionally, it revealed fragmentation of A1BG in several patients and the bottom range bands tended to be most prominently elevated in IgAN patients. Mass spectrometry confirmed differences between the diseases according to the specific amino acids fragments of each tested protein. Figure 1. Western blot scans for urinary A1BG, ORM-1 and FTL in CKD patients (2-4) and healthy controls (1). CONCLUSIONS: The urinary concentrations of A1BG, ORM-1, FTL and TF are elevated in CKD patients and vary depending on the type of nephropathy. This observation suggests their differential roles in the pathophysiology of the given diseases, and we believe their evaluation may help distinguishing between nephropathies. Further studies are desired to establish the role of these urinary proteins in non-invasive disease differentiation

Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study

Background: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers. Methods: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire. Results: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times. Conclusion: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx. (C) 2017 S. Karger AG, Basel.Peer reviewe

Interrogation of gossypol therapy in glioblastoma implementing cell line and patient-derived tumour models

Background: Glioblastoma (GBM), being a highly vascularised and locally invasive tumour, is an attractive target for anti-angiogenic and anti-invasive therapies. The GBM/endothelial cell response to gossypol/temozolomide (TMZ) treatment was investigated with a particular aim to assess treatment effects on cancer hallmarks. Methods: Cell viability, endothelial tube formation and GBM tumour cell invasion were variously assessed following combined treatment in vitro. The U87MG-luc2 subcutaneous xenograft model was used to investigate therapeutic response in vivo. Viable tumour response to treatment was interrogated using immunohistochemistry. Combined treatment protocols were also tested in primary GBM patient-derived cultures. Results: An endothelial/GBM cell viability inhibitory effect, as well as an anti-angiogenic and anti-invasive response, to combined treatment have been demonstrated in vitro. A significantly greater anti-proliferative (P=0.020, P=0.030), anti-angiogenic (P=0.040, P<0.0001) and pro-apoptotic (P=0.0083, P=0.0149) response was observed when combined treatment was compared with single gossypol/TMZ treatment response, respectively. GBM cell line and patient-specific response to gossypol/TMZ treatment was observed. Conclusions: Our results indicate that response to a combined gossypol/TMZ treatment is related to inhibition of tumour-associated angiogenesis, invasion and proliferation and warrants further investigation as a novel targeted GBM treatment strategy

Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen

Author manuscript: 2010 September 22.Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers[superscript 1, 2]. The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag- and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas—an organ that critically requires cyclin D1 function[superscript 3, 4]—cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1-/-) retinas. Transduction of an activated allele of Notch1 into Ccnd1-/- retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term ‘genetic–proteomic’, can be used to study the in vivo function of essentially any protein