Sheep α-globin gene sequences: Implications for their concerted evolution and for the down-regulation of the 3' genes

In sheep as in man and most other mammals, there are two α-globin genes (Iα and IIα), which are expressed at different levels, the upstream gene being the most efficient. In α-globin gene triplication and quadruplication, this trend is confirmed, i.e., the α-chain output of the downstream genes progressively decreases. In this study, we have determined the complete sequence of the cDNAs and of both the introns in a triple-α haplotype in which each gene could be recognized for the presence of distinct alleles. The sequence analysis reveals that the bodies of the three α-globin genes are essentially identical (99.9% homology) and moreover indicates that the down-regulation of additional α-globin genes in sheep is not the effect of sequence variation from the Cap to the Poly(A) addition sites. This striking similarity among α-genes is higher than that seen in other mammals and is probably sustained by particularly efficient mechanisms of gene conversion and cross-over fixation

Main roads to melanoma

The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways

Role of the EGF +61A>G polymorphism in melanoma pathogenesis: an experience on a large series of Italian cases and controls

<p>Abstract</p> <p>Background</p> <p>A single nucleotide polymorphism (61A>G) in the epidermal growth factor (<it>EGF</it>) gene has been implicated in both melanoma pathogenesis and increased melanoma risk. To further evaluate this association, we conducted a case-control study in a clinic-based Italian population.</p> <p>Methods</p> <p>Individuals with less than 10 (N = 127) or more than 100 (N = 128) benign nevi, and patients with cutaneous melanoma (N = 418) were investigated for the <it>EGF </it>+61A>G polymorphism, using an automated sequencing approach.</p> <p>Results</p> <p>Overall, no difference in <it>EGF </it>genotype frequencies was observed among subjects with different number of nevi as well as when non-melanoma healthy controls were compared with the melanoma patients. However, a heterogeneous distribution of the frequencies of the G/G genotype was detected among cases and controls originating from North Italy (21.1 and 18.3%, respectively) vs. those from South Italy (12.6 and 17.1%, respectively).</p> <p>Conclusion</p> <p>Our findings further suggest that <it>EGF </it>+61A>G polymorphism may have a limited impact on predisposition and/or pathogenesis of melanoma and its prevalence may vary in different populations.</p

The MASSIMO system for the safeguarding of historic buildings in a seismic area: operationally-oriented platforms

In this paper, the non-invasive system MASSIMO is presented for the monitoring and the seismic vulnerability mitigation of the cultural heritage. It integrates ground-based, airborne and space-borne remote sensing tools with geophysical and in situ surveys to provide the multi-spatial (regional, urban and building scales) and multi-temporal (long-term, short-term, near-real-time and real-time scales) monitoring of test areas and buildings. The measurements are integrated through web-based GIS and 3D visual platforms to support decision-making stakeholders involved in urban planning and structural requalification. An application of this system is presented over the Calabria region for the town of Cosenza and a test historical complex

Role of the <i>EGF</i> +61A&gt;G polymorphism in melanoma pathogenesis: an experience on a large series of Italian cases and controls

Background. A single nucleotide polymorphism (61A&gt;G) in the epidermal growth factor (EGF) gene has been implicated in both melanoma pathogenesis and increased melanoma risk. To further evaluate this association, we conducted a case-control study in a clinic-based Italian population. Methods. Individuals with less than 10 (N = 127) or more than 100 (N = 128) benign nevi, and patients with cutaneous melanoma (N = 418) were investigated for the EGF +61A&gt;G polymorphism, using an automated sequencing approach. Results. Overall, no difference in EGF genotype frequencies was observed among subjects with different number of nevi as well as when non-melanoma healthy controls were compared with the melanoma patients. However, a heterogeneous distribution of the frequencies of the G/G genotype was detected among cases and controls originating from North Italy (21.1 and 18.3%, respectively) vs. those from South Italy (12.6 and 17.1%, respectively). Conclusion. Our findings further suggest that EGF +61A&gt;G polymorphism may have a limited impact on predisposition and/or pathogenesis of melanoma and its prevalence may vary in different populations

Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe : an ERA Registry study

Background The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. Methods Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. Results The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]. Conclusion This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe.Peer reviewe

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

A study of sertraline in dialysis (ASSertID) : a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis

© 2015 Friedli et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBACKGROUND: The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder.METHODS/DESIGN: The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial.DISCUSSION: There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression.TRIAL REGISTRATION: ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.Peer reviewedFinal Published versio

The ERA-EDTA Registry Annual Report 2017 : a summary

Background. This article presents a summary of the 2017 Annual Report of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 37 countries. Methods. The ERA-EDTA Registry received individual patient data on patients undergoing RRT for ESRD in 2017 from 32 national or regional renal registries and aggregated data from 21 registries. The incidence and prevalence of RRT, kidney transplantation activity and survival probabilities of these patients were calculated. Results. In 2017, the ERA-EDTA Registry covered a general population of 694 million people. The incidence of RRT for ESRD was 127 per million population (pmp), ranging from 37 pmp in Ukraine to 252 pmp in Greece. A total of 62% of patients were men, 52% were >= 65 years of age and 23% had diabetes mellitus as the primary renal disease. The treatment modality at the onset of RRT was haemodialysis for 85% of patients. On 31 December 2017, the prevalence of RRT was 854 pmp, ranging from 210 pmp in Ukraine to 1965 pmp in Portugal. The transplant rate in 2017 was 33 pmp, ranging from 3 pmp in Ukraine to 103 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2008-12, the unadjusted 5-year patient survival probability for all RRT modalities combined was 50.8%.Peer reviewe