Electronic health use in the european union and the effect of multimorbidity: Cross-sectional survey

Background: Multimorbidity is becoming increasingly common and is a leading challenge currently faced by societies with aging populations. The presence of multimorbidity requires patients to coordinate, understand, and use the information obtained from different health care professionals, while simultaneously striving to distinguish the symptoms of different diseases and self-manage their sometimes conflicting health problems. Electronic health (eHealth) tools provide a means to disseminate health information and education for both patients and health professionals and hold promise for more efficient and cost-effective care processes. Objective: The aim of this study was to analyze the use of eHealth tools, taking into account the citizens' sociodemographic and clinical characteristics, and above all, the presence of multimorbidity. Methods: Cross-sectional and exploratory research was conducted using online survey data from July 2011 to August 2011. Participants included a total of 14,000 citizens from 14 European countries aged 16 to 74 years, who had used an eHealth tool in the past 3 months. The variables studied were sociodemographic variables of the participants, the questionnaire items assessing the frequency of using eHealth tools, the degree of morbidity, and the eHealth adoption gradient. Chi-square tests were conducted to examine the relationship between the sociodemographic and clinical variables of participants and the group the participants were assigned to according to their frequency of eHealth use (eHealth user group). A one-way analysis of variance (ANOVA) allowed for assessing the differences in the eHealth adoption gradient average between different groups of individuals according to their morbidity level. A two-way between-groups ANOVA was performed to explore the effects of multimorbidity and age group on the eHealth adoption gradient. Results: According to the eHealth adoption gradient, most participants (68.15%, 9541/14,000) were labeled as rare users, with the majority of them (55.1%, 508/921) being in the age range of 25 to 54 years, with upper secondary education (50.3%, 464/921), currently employed (49.3%, 454/921), and living in medium-sized cities (40.7%, 375/921). Results of the one-way ANOVA showed that the number of health problems significantly affected the use of eHealth tools (F-2,F-13996=11.584; P<.001). The two-way ANOVA demonstrated that there was a statistically significant interaction between the effects of age and number of health problems on the eHealth adoption gradient (F-4,F-11991=7.936; P<.001). Conclusions: The eHealth adoption gradient has proven to be a reliable way to measure different aspects of eHealth use. Multimorbidity is associated with a more intense use of eHealth, with younger Internet users using new technologies for health purposes more frequently than older groups with the same level of morbidity. These findings suggest the need to consider different strategies aimed at making eHealth tools more sensitive to the characteristics of older populations to reduce digital disadvantages

La risa de Quevedo

Background Rectal duplication cysts are rare gastrointestinal congenital duplicate cysts with various clinical presentations that require different management. Case presentation We present a case of a lady with a double rectal duplicate cyst which was found incidentally on a follow-up CT abdomen and pelvis scan. The patient initially had a mucocele excision, and following that, she had a non-contrast CT abdomen and pelvis to investigate post-operative pain. The CT scan revealed a single rectal duplicate cyst. She had a posterior approach excision to have it removed, and only intra-operatively, she was found to have a double rectal duplicate cyst. She had them both removed via a midline incision running from the perineal pigmentation and extending until the coccyx. She had another follow-up CT which showed complete excision of the cysts. Conclusions After a thorough review of the literature regarding rectal cysts, there was no mention of a double rectal duplicate cyst. The purpose of this paper is to point out the various potential presentations of a rectal cyst as well as the idea that a double cyst is managed effectively in a similar way as the single one

Inhibiting DNA methylation as a strategy to enhance adipose-derived stem cells differentiation. Focus on the role of Akt/mTOR and Wnt/β-catenin pathways on adipogenesis

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, due to their ability to repair damaged tissues and to mitigate the inflammatory/immune response. A better understanding of the underlying mechanisms regulating ASC biology might represent the chance to modulate their in vitro characteristics and differentiation potential for regenerative medicine purposes. Herein, we investigated the effects of the demethylating agent 5-azacytidine (5-aza) on proliferation, clonogenicity, migration, adipogenic differentiation and senescence of ASCs, to identify the molecular pathways involved. Through functional assays, we observed a detrimental effect of 5-aza on ASC self-renewal capacity and migration, accompanied by actin cytoskeleton reorganization, with decreased stress fibers. Conversely, 5-aza treatment enhanced ASC adipogenic differentiation, as assessed by lipid accumulation and expression of lineage-specific markers. We analyzed the involvement of the Akt/mTOR, MAPK and Wnt/beta-catenin pathways in these processes. Our results indicated impairment of Akt and ERK phosphorylation, potentially explaining the reduced cell proliferation and migration. We observed a 5-aza-mediated inhibition of the Wnt signaling pathway, this potentially explaining the pro-adipogenic effect of the drug. Finally, 5-aza treatment significantly induced ASC senescence, through upregulation of the p53/p21 axis. Our data may have important translational implications, by helping in clarifying the potential risks and advantages of using epigenetic treatment to improve ASC characteristics for cell-based clinical approaches

Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype

<p>Abstract</p> <p>Background</p> <p>Carriers of apparently balanced translocations are usually phenotypically normal; however in about 6% of <it>de novo </it>cases, an abnormal phenotype is present. In the current study we investigated 12 patients, six <it>de novo </it>and six familial, with apparently balanced translocations and mental retardation and/or congenital malformations by applying 1 Mb resolution array-CGH. In all <it>de novo </it>cases, only the patient was a carrier of the translocation and had abnormal phenotype. In five out of the six familial cases, the phenotype of the patient was abnormal, although the karyotype appeared identical to other phenotypically normal carriers of the family. In the sixth familial case, all carriers of the translocations had an abnormal phenotype.</p> <p>Results</p> <p>Chromosomal and FISH analyses suggested that the rearrangements were "truly balanced" in all patients. However, array-CGH, revealed cryptic imbalances in three cases (3/12, 25%), two <it>de novo </it>(2/12, 33.3%) and one familial (1/12, 16.6%). The nature and type of abnormalities differed among the cases. In the first case, what was identified as a <it>de novo </it>t(9;15)(q31;q26.1), a complex rearrangement was revealed involving a ~6.1 Mb duplication on the long arm of chromosome 9, an ~10 Mb deletion and an inversion both on the long arm of chromosome 15. These imbalances were located near the translocation breakpoints. In the second case of a <it>de novo </it>t(4;9)(q25;q21.2), an ~6.6 Mb deletion was identified on the short arm of chromosome 7 which is unrelated to the translocation. In the third case, of a familial, t(4;7)(q13.3;p15.3), two deletions of ~4.3 Mb and ~2.3 Mb were found, each at one of the two translocation breakpoints. In the remaining cases the translocations appeared balanced at 1 Mb resolution.</p> <p>Conclusion</p> <p>This study investigated both <it>de novo </it>and familial apparently balanced translocations unlike other relatively large studies which are mainly focused on <it>de novo </it>cases. This study provides additional evidence that cryptic genomic imbalances are common in patients with abnormal phenotype and "apparently balanced" translocations not only in <it>de novo </it>but can also occur in familial cases. The use of microarrays with higher resolution such as oligo-arrays may reveal that the frequency of cryptic genomic imbalances among these patients is higher.</p

Otx015 epi‐drug exerts antitumor effects in ovarian cancer cells by blocking gnl3‐mediated radioresistance mechanisms: Cellular, molecular and computational evidence

Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra‐Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015‐mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC

Differential DNA Methylation Encodes Proliferation and Senescence Programs in Human Adipose-Derived Mesenchymal Stem Cells

Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 5′-azacitidine (5′-AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified “phagocytosis,” “type 2 diabetes,” and “metabolic pathways” as disproportionately hypomethylated, whereas “adipocyte differentiation” was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs

Calcineurin gamma catalytic subunit ppp3cc inhibition by mir-200c-3p affects apoptosis in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients

Cobomarsen, an oligonucleotide inhibitor of miR-155, slows DLBCL tumor cell growth in vitro and in vivo

MicroRNA-155, is an oncogenic miRNA, highly expressed in B-cell malignancies, particularly in the non-Germinal Center B-cell or activated B-cell subtype of Diffuse Large B-cell Lymphoma (non-GCB/ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL

X-box binding protein 1 induces the expression of the lytic cycle transactivator of Kaposi's sarcoma-associated herpesvirus but not Epstein–Barr virus in co-infected primary effusion lymphoma

Cells of primary effusion lymphoma (PEL), a B-cell non-Hodgkin's lymphoma, are latently infected by Kaposi's sarcoma-associated herpesvirus (KSHV), with about 80 % of PEL also co-infected with Epstein–Barr virus (EBV). Both viruses can be reactivated into their lytic replication cycle in PEL by chemical inducers. However, simultaneous activation of both lytic cascades leads to mutual lytic cycle co-repression. The plasma cell-differentiation factor X-box binding protein 1 (XBP-1) transactivates the KSHV immediate–early promoter leading to the production of the replication and transcription activator protein (RTA), and reactivation of KSHV from latency. XBP-1 has been reported to act similarly on the EBV immediate–early promoter Zp, leading to the production of the lytic-cycle transactivator protein BZLF1. Here we show that activated B-cell terminal-differentiation transcription factor X-box binding protein 1 (XBP-1s) does not induce EBV BZLF1 and BRLF1 expression in PEL and BL cell lines, despite inducing lytic reactivation of KSHV in PEL. We show that XBP-1s transactivates the KSHV RTA promoter but does not transactivate the EBV BZLF1 promoter in non-B-cells by using a luciferase assay. Co-expression of activated protein kinase D, which can phosphorylate and inactivate class II histone deacetylases (HDACs), does not rescue XBP-1 activity on Zp nor does it induce BZLF1 and BRLF1 expression in PEL. Finally, chemical inducers of KSHV and EBV lytic replication in PEL, including HDAC inhibitors, do not lead to XBP-1 activation. We conclude that XBP-1 specifically reactivates the KSHV lytic cycle in dually infected PELs