Impact of different levels of handling on Solea senegalensis culture: effects on growth and molecular markers of stress.

Aquaculture routine practices may cause stress induction on the fish and compromise their welfare affecting the production. This experiment aimed to evaluate the potential links between handling during culture with stress responses and growth on Senegalese sole (Solea senegalensis). We worked with two fish cohorts in terms of initial body weight and culture stage: Trial 1 included specimens in the fattening stage (226 ± 4.96 g) and Trial 2 animals in the pre-fattening stage (27.20 ± 0.44 g). The tested culture protocol, which lasted 6 and 4 months for Trial 1 and 2, respectively, mainly reduced handling-derived stressors in the experimental tanks via lowering routine samplings to a minimum. This decrease of the handling-derived stress was reflected in both trials with lower concentration of circulating cortisol in blood plasma from the experimental fish when compared to controls. Moreover, the proposed protocol promoted higher growth in the fish cultured in the less disturbing protocol in Trial 2. Higher specific growth rates and mean body weight and length were reported. In order to further explore the potential beneficial effects of our protocol, we studied the musculoskeletal from Trial 2 gene expression of key genes regulating glucocorticoid signaling pathway and apoptosis: glucocorticoid receptors 1 and 2 (gr1, gr2), heat shock protein 90 AA (hsp90aa), and caspase 6 (casp6). In line with the cortisol reduced level in this trial, gr1, hsp90aa, and casp6 genes showed lower expression in the samples coming from the experimental group. The findings of this study provide valuable information to the aquaculture industry for the management of Solea senegalensis stress and welfare.

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir.

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.

Suggestions for Improvements in National Radon Control Strategies of Member States Which Were Developed as a Requirement of EU Directive 2013/59 EURATOM.

Exposure to the indoor air pollutant radon is considered to be a significant health risk globally, as has been demonstrated by many studies over time. A recent WHO statement on radon estimates that, worldwide, approximately 80,000 people may die every year due to lung cancer associated with radon exposure. The recent years have also seen huge improvements in radon policies in European countries, as a consequence of the issuing, in 2013, of the Council Directive 2013/59/Euratom. Although the protection of workers from radon exposure is well established, the protection of the general public needs more improvements. The main objective of this paper is, first, to acknowledge and recognise the improvements in radon protection policies, but also to show that there are many areas where improvements are desirable and possible. The final goal is to suggest better ways to protect the general population from exposure to radon gas. The suggestions are based on the experiences of the co-authors, who come from different disciplines related to radon management. The following fields or areas where improvements are possible are identified: risk communication, building codes, radon policies, including funding, research and protection of children. We describe the work that has been conducted, and the possible improvements and solutions in these fields.

Long-term efficacy and safety profiles following small incision lenticule extraction in eyes with ≥ 5-year follow-up.

PURPOSE: To evaluate long-term efficacy, safety, predictability and stability (refractive and keratometric) of myopic and myopic astigmatism correction with Small Incision Lenticule Extraction (SMILE). METHODS: Single center retrospective review of eyes undergoing SMILE from 2012-2015. Forty-two eyes (23 patients) with ≥ 5-year follow-up. Variables analyzed were preoperative, 3-month, 1-year and last follow-up uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, spherical equivalent (SE) and mean keratometry. Descriptive statistics were performed and results reported following the Standard for Reporting Astigmatism Outcomes. RESULTS: Mean follow-up of 5.98 ± 0.90 years. Mean preoperative SE was -5.26 ± 1.22D (range -2.50 to -8.12D). Mean preoperative cylinder was -0.66 ± 0.61D (range 0.00 to -2.25D). Efficacy and safety indices were 0.86 and 0.98, respectively. In total, 81% of operated eyes achieved an UDVA of ≥ 0.09 logMar (20/25 Snellen). At the last follow-up, ≥1 line of CDVA was gained in 14% of eyes. Five percent lost 1 line of CDVA, and no eye loss ≥2 lines of CDVA. Sixty-nine percent of eyes were within ± 0.50D and 86% within ± 1.00D of the attempted SE correction. Ninety-one percent of eyes had ≤0.50D of postoperative astigmatism and 71% were within ± 15° from the intended correction axis. At the final follow-up, a statistically significant myopic regression of 0.19 ± 0.50D was observed (p = 0.01). CONCLUSIONS: Long-term results demonstrate that SMILE is effective, predictable and safe. SMILE has good stability, low regression compared to LASIK, and no signs of corneal ectasia staging within our standard criteria.

Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells.

Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call 'progestin control regions' (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.

Association between Heart Failure and Clinical Prognosis in Patients with Acute Ischemic Stroke: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: Ischemic stroke is a common cause of death worldwide. In clinical practice it is observed that many individuals who have experienced an ischemic stroke also suffer from simultaneous comorbidities such as heart failure, which could be directly associated with a worse clinical prognosis. Therefore, this study analyzed outcomes in terms of the severity of the event, inhospital mortality, duration of hospital stay, and inhospital recurrence of the episode, in order to determine the implications resulting from the presentation of both pathologies. METHODS: This was a retrospective-cohort, hospital-based study. RESULTS: The study included 110 subjects with heart failure (exposed) and 109 subjects without heart failure (nonexposed). The incidence of inhospital mortality was 27.27% in exposed patients and 9.17% in nonexposed patients (p<0.001), and the presence of heart failure increased the risk of death by 92% (p=0.027). According to scores on the National Institutes of Health Stroke Scale, the median severity was worse in exposed than nonexposed patients (16.1 vs. 9.2, p =0.001). The median hospital stay was 9 days in subjects with heart failure and 7 days in nonexposed patients (p=0.011). The rate of inhospital stroke did not differ significantly between exposed and nonexposed patients (1.82% vs. 0.92%, p=0.566). CONCLUSIONS: Individuals with heart failure who suffer from an acute ischemic stroke show worse clinical outcomes in terms of mortality, event severity, and duration of hospital stay.

A SIMPLE NATIONAL INTERCOMPARISON OF RADON IN WATER.

Radon-222, a naturally occurring radioactive gas, responsible together with its progeny of around 50% of the average effective dose received by the population, has not been regulated by law until the recent Directive 2013/51 /Euratom. Its transposition into Spanish legislation was made in the recent RD 314/2016, which sets at limit value of 500 Bq l-1 for radon-222 in water for human consumption. Intercomparison exercises, such as those carried out by IPROMA SL and the Laboratory of Environmental Radioactivity of the Cantabria University (LARUC) in November 2015 and December 2016, represent the most useful tool available for detecting problems and taking corrective actions necessary for an efficient measurement by part of the laboratories. The participants in these exercises used three techniques: liquid scintillation counting, gamma spectrometry and desorption followed by ionisation chamber detection.

Participación en el sector no agropecuario en el México rural: una perspectiva de género / Participação no setor não agrícola no México rural: uma perspectiva de gênero / Participation in the non-agricultural sector in rural Mexico: a gender perspective

Los hogares rurales diversifican sus ingresos como estrategia para minimizar los riesgos, reducir la variabilidad y asegurar un nivel mínimo de ingreso. Con información panel de la Encuesta Nacional a Hogares Rurales de México, el presente estudio examina, bajo una perspectiva de género, los factores que determinan la participación en el sector no agropecuario. Los resultados señalan que en las ocupaciones asalariadas no agropecuarias, los hombres participan con menores niveles de escolaridad y la condición de indígena limita la incorporación de ambos géneros. En actividades no agropecuarias por cuenta propia son esenciales la riqueza acumulada del hogar y los servicios financieros, de comunicación y transporte.

As famílias rurais diversificam sua renda como estratégia para minimizar o risco, reduzir a variabilidade e garantir um nível mínimo de renda. Com informações da Encuesta Nacional a Hogares Rurales de México, o presente estudo examinou, sob uma perspectiva de gênero, os fatores que determinam a participação no setor não agrícola. Os resultados indicam que, nas ocupações assalariadas não agrícolas, os homens participam com baixos níveis de escolaridade e a situação indígena limita a incorporação de ambos os sexos. Em atividades de autoemprego não agrícola, são essenciais a riqueza acumulada das famílias e serviços financeiros, de comunicação e transporte.

Rural households diversify their income as a strategy to minimize risk, reduce variability and ensure a minimum level of income. With information panel of the National Rural Household Survey of Mexico, this study examined under a gender perspective, the factors that determine participation in the non-agricultural sector. The results indicate that employed in non-agricultural occupations, men participate with lower levels of education and indigenous status limits the incorporation of both genders. In non-agricultural self-employment activities are essential household accumulated wealth and financial services, communication and transportation.

Una aproximación a los valores distintivos del médico / An approach to the distinctive values of the physician

La educación del carácter resulta esencial en la formación del médico. El objetivo de este estudio ha sido evaluar las cualidades del carácter de los futuros médicos y compararlas con las de estudiantes de otras disciplinas. Para ello se hizo uso del sistema de clasificación de las fortalezas y virtudes personales que ha sido ampliamente utilizado en diferentes países y muestras. Tres muestras de estudiantes universitarios participaron en el estudio: Medicina (n = 75); Psicología (n = 71) y Ciencias Económicas y Empresariales (n = 60). Los participantes completaron el instrumento Values in Action Inventory of Strengths (VIA-IS) y la Escala de Afecto Positivo y Negativo (PANAS). Las fortalezas más autoadscritas por los tres grupos fueron la bondad, el amor, la justicia, la gratitud y la honestidad, aunque diferían en el orden de clasificación. Los análisis de covarianza controlando el sexo y las emociones positivas y negativas mostraron que los estudiantes de Medicina presentaban puntuaciones significativamente más altas en perseverancia, perspectiva, prudencia y perdón que los estudiantes de Psicología. Del mismo modo, los estudiantes de Medicina tuvieron puntuaciones significativamente más altas en justicia, humildad, bondad y curiosidad que los estudiantes de Ciencias Económicas y Empresariales. Estos resultados preliminares muestran algunas diferencias significativas en el perfil de fortalezas de los próximos médicos. Se sugieren nuevas posibilidades de investigación y de formación en esta área educativa emergente

Character education is essential in the physician training. The aim of this study was to assess character strengths of Medicine students and compare them to students from different disciplines. For this purpose, the character strengths and virtues classification was used, a model that has been widely used in different countries and samples. Three different samples of university students participated in the study [Medicine (n=75), Psychology (n=71) and Economics (n=60)]. Participants filled out the Values in Action Inventory of Strengths (VIAIS) and the Positive and Negative Affective Questionnaire (PANAS). Kindness, love, fairness, gratitude and honesty were the signature strengths of the three groups, although classification order differed. Covariance analyses controlling for sex and positive and negative emotions showed that Medical students reported significantly higher scores on perseverance, perspective, prudence and forgiveness than Psychology students. Likewise, Medical students had significantly higher scores on fairness, humility, kindness and curiosity than Economics students. These preliminary results show some significant differences in the profile of wouldbe physicians. Possibilities for future research and training in this emerging educational area are suggested