Long-term exhaustion of the inbreeding load in Drosophila melanogaster

Inbreeding depression, the decline in fitness of inbred individuals, is a ubiquitous phenomenon of great relevance in evolutionary biology and in the fields of animal and plant breeding and conservation. Inbreeding depression is due to the expression of recessive deleterious alleles that are concealed in heterozygous state in noninbred individuals, the so-called inbreeding load. Genetic purging reduces inbreeding depression by removing these alleles when expressed in homozygosis due to inbreeding. It is generally thought that fast inbreeding (such as that generated by full-sib mating lines) removes only highly deleterious recessive alleles, while slow inbreeding can also remove mildly deleterious ones. However, a question remains regarding which proportion of the inbreeding load can be removed by purging under slow inbreeding in moderately large populations. We report results of two long-term slow inbreeding Drosophila experiments (125–234 generations), each using a large population and a number of derived lines with effective sizes about 1000 and 50, respectively. The inbreeding load was virtually exhausted after more than one hundred generations in large populations and between a few tens and over one hundred generations in the lines. This result is not expected from genetic drift alone, and is in agreement with the theoretical purging predictions. Computer simulations suggest that these results are consistent with a model of relatively few deleterious mutations of large homozygous effects and partially recessive gene action

Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage

DAQUA-MASS: An ISO 8000-61 Based Data Quality Management Methodology for Sensor Data

The Internet-of-Things (IoT) introduces several technical and managerial challenges when it comes to the use of data generated and exchanged by and between various Smart, Connected Products (SCPs) that are part of an IoT system (i.e., physical, intelligent devices with sensors and actuators). Added to the volume and the heterogeneous exchange and consumption of data, it is paramount to assure that data quality levels are maintained in every step of the data chain/lifecycle. Otherwise, the system may fail to meet its expected function. While Data Quality (DQ) is a mature field, existing solutions are highly heterogeneous. Therefore, we propose that companies, developers and vendors should align their data quality management mechanisms and artefacts with well-known best practices and standards, as for example, those provided by ISO 8000-61. This standard enables a process-approach to data quality management, overcoming the difficulties of isolated data quality activities. This paper introduces DAQUA-MASS, a methodology based on ISO 8000-61 for data quality management in sensor networks. The methodology consists of four steps according to the Plan-Do-Check-Act cycle by Deming.This work was primarily funded by DQIoT project (Eureka program, E!11737; and CDTI (Centro Para el Desarrollo Tecnológico Industrial), INNO-20171086). Additionally, this work was partially funded by SEQUOIA project (TIN2015-63502-C3-1-R and TIN2015-63502-C3-3-R) (MINECO/FEDER); GEMA SBPLY/17/180501/000293, Consejería de Educación, Cultura y Deporte de la Dirección General de Universidades, Investigación e Innovación de la JCCM); ECD project (Evaluación y Certificación de la Calidad de Datos) (PTQ-16-08504) (Torres Quevedo Program, MINECO). Finally, it was also supported through a grant to Ricardo Pérez-Castillo enjoys from JCCM within the initiatives for talent retention and return in line with RIS3 goals

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes

OBJECTIVE: Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. METHODS: We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. RESULTS: A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. SIGNIFICANCE: Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful

Allogeneic Hematopoietic Stem Cell Transplantation in Transformed Follicular Lymphoma (tFL): Results of a Retrospective Multicenter Study from GELTAMO/GETH-TC Spanish Groups

Simple Summary Follicular lymphoma (FL) is the most prevalent subtype of indolent lymphoma, accounting for 70% of all cases. The estimated risk of histological transformation (tFL), such as diffuse large B cell lymphoma (DLBCL), varies from 2-3% per year to 7-8% at 10 years in different series. Treatment after transformation is not clearly established. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be an option for these patients, but it has not been widely explored. We analyze the efficacy and toxicity of alloSCT in 43 patients from 14 Spanish centers. We observed long-term survival in around one third of the patients, especially those who developed chronic graft versus host disease, indicating that alloSCT continues to be a potentially curative option for patients with tFL, mainly due to the graft versus lymphoma effect. Background: Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be a potentially curative option for these patients, but it has not been widely explored. Methods: We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival. Results: A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6). Conclusions: Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL

The Fluid Aspect of the Mediterranean Diet in the Prevention and Management of Cardiovascular Disease and Diabetes: The Role of Polyphenol Content in Moderate Consumption of Wine and Olive Oil

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism

Eina d'ajuda a la presa de decisions compartides en anticoncepció: guia d’implementació

Anticoncepció; Assessorament contraceptiu; Presa de decisionsAnticoncepción; Asesoramiento contraceptivo; Toma de decisionesContraception; Contraceptive counseling; Decision makingLa present guia té com a objectiu facilitar la implementació d’aquesta eina als professionals de la salut que ofereixen assessorament contraceptiu. Les EAPD són intervencions dissenyades per ajudar en la presa de decisions específiques, tot detallant les diferents alternatives disponibles (diagnòstiques, terapèutiques o de prevenció), amb els seus avantatges i desavantatges. Incorporen elements que permeten a les persones manifestar els seus valors i preferències, facilitant així una decisió conjunta i acompanyada per professionals de salut.La presente guía tiene como objetivo facilitar la implementación de esta herramienta a los profesionales de la salud que ofrecen asesoramiento contraceptivo. Las EAPD son intervenciones diseñadas para ayudar en la toma de decisiones específicas, detallando las diferentes alternativas disponibles (diagnósticas, terapéuticas o de prevención), con sus ventajas y desventajas. Incorporan elementos que permiten a las personas manifestar sus valores y preferencias, facilitando así una decisión conjunta y acompañada por profesionales de salud.The aim of this guide is to facilitate the implementation of this tool for health professionals who offer contraceptive advice. EAPDs are interventions designed to help in making specific decisions, while detailing the different alternatives available (diagnostic, therapeutic or preventive), with their advantages and disadvantages. They incorporate elements that allow people to express their values and preferences, thus facilitating a joint decision accompanied by health professionals

Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia:the PETHEMA-PALG experience

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA “chemotherapy based” and “chemotherapy free” protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8–231.1): 43.3 (range: 2.8–113.9) for s-MDS/AML and 61.7 (range: 7.1–231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p &lt; 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.</p