Identification of conserved genes triggering puberty in European sea bass males (Dicentrarchus labrax) by microarray expression profiling.

BACKGROUND: Spermatogenesis is a complex process characterized by the activation and/or repression of a number of genes in a spatio-temporal manner. Pubertal development in males starts with the onset of the first spermatogenesis and implies the division of primary spermatogonia and their subsequent entry into meiosis. This study is aimed at the characterization of genes involved in the onset of puberty in European sea bass, and constitutes the first transcriptomic approach focused on meiosis in this species. RESULTS: European sea bass testes collected at the onset of puberty (first successful reproduction) were grouped in stage I (resting stage), and stage II (proliferative stage). Transition from stage I to stage II was marked by an increase of 11ketotestosterone (11KT), the main fish androgen, whereas the transcriptomic study resulted in 315 genes differentially expressed between the two stages. The onset of puberty induced 1) an up-regulation of genes involved in cell proliferation, cell cycle and meiosis progression, 2) changes in genes related with reproduction and growth, and 3) a down-regulation of genes included in the retinoic acid (RA) signalling pathway. The analysis of GO-terms and biological pathways showed that cell cycle, cell division, cellular metabolic processes, and reproduction were affected, consistent with the early events that occur during the onset of puberty. Furthermore, changes in the expression of three RA nuclear receptors point at the importance of the RA-signalling pathway during this period, in agreement with its role in meiosis. CONCLUSION: The results contribute to boost our knowledge of the early molecular and endocrine events that trigger pubertal development and the onset of spermatogenesis in fish. These include an increase in 11KT plasma levels and changes in the expression of several genes involved in cell proliferation, cell cycle progression, meiosis or RA-signalling pathway. Moreover, the results can be applied to study meiosis in this economically important fish species for Mediterranean countries, and may help to develop tools for its sustainable aquaculture.

Preferences for patient medication information: what do patients want?

This study investigated respondent preferences on how best to display patient medication information (PMI) that accompanies prescription medications to promote comprehension and appropriate usage. The authors identified 30 individuals diagnosed with select immune disorders, 30 with other chronic diseases, and 30 from the general public and had them review one of two PMI handouts that varied by format, organization, and content. The authors explored preferences for the PMI handout using one-on-one interviews. The authors analyzed the qualitative data to identify relevant themes and patterns using NVivo9 qualitative software. The majority of respondents noted that the formats of the two PMI handouts were more informative than those they currently receive from the pharmacist, with a preference for the 2-column, segmented design. However, respondent PMI preferences varied by age, education, and health status. Patients need simpler and more concise drug information to make better decisions about their health. Current PMI handouts are dense and complex, which can be confusing and not reader friendly. To improve PMI understandability and usefulness, the U.S. Food and Drug Administration is working with stakeholders, consumer advocates, and academics. Findings from this study may help inform future development of more user-friendly PMI.

Prioritisation of pesticides and target organ systems for dietary cumulative risk assessment based on the 2019-2021 monitoring cycle.

Aiming at accelerating the implementation of cumulative risk assessment to pesticide residues, this report describes a two-step prioritisation analysis, on individual pesticides and on target organ systems, that allows to identify (i) low-priority substances expected to have a marginal contribution to cumulative risk, and (ii) high priority organ systems to be addressed in future cumulative risk assessments. The analysis encompassed 350 substances and 36 raw primary commodities of plant origin surveyed in the monitoring cycle 2019-2021, carried out in 30 population groups, covering 3 age classes, and 17 EU countries. Probabilistic exposure calculations, for chronic and acute effects, were executed on the occurrence and consumption data by a two-dimensional procedure, modelling variability and uncertainty. In the first step, the prioritisation method adopted allowed to reduce the number of substances by about 80%. These substances were in turn grouped based on their capacity to cause toxicological effects on common organ systems and, as second step, probabilistic combined exposure calculations were carried out for 16 target organ systems. This step allowed to identify the organ systems that need further assessment, reducing their initial number by about 70%. The organ systems would need to be prioritised as follows: reproductive and developmental toxicity, liver, kidney, male reproductive system, and haematopoietic system and haematology. The sources of uncertainty stemming from the modelling procedure and from methodological assumptions were discussed and their impact qualitatively assessed. Overall, it was concluded that the risk estimates for the different organ systems were more likely to be overestimated than underestimated.

Comparison of quality of life after radical treatment in prostate cancer: radical prostatectomy versus external radiotherapy.

OBJECTIVE: To assess and compare the functional and quality of life results in patients treated with curative intent for localized prostate cancer during 2015 in our hospital. METHOD: 77 patients treated by radical prostatectomy or external radiotherapy with androgen deprivation were prospective enrolled. Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) questionnaire at 3-year follow-up and Spanish Questionnaire on Quality of Life in Patients with Prostate Cancer (CAVIPRES-30) at diagnosis and at 3-year follow-up were registered. RESULTS: 68 patients were included, 39 patients treated by radical prostatectomy and 29 received external radiotherapy with androgen deprivation. Among the operated patients, 61.5% were dry and 17.9% use three or more daily pads, compared to 72.4% and 6.8%, respectively, in the radiotherapy group. 48.7% of prostatectomized patients reported very poor or no capacity to have a sufficiently rigid erection, compared to 69% of the radiated group. After surgery, 43.6% considered bad or very bad quality-of-life, compared to 68.9% in the radiotherapy group. In the comparison of the data of the pre- and post-treatment questionnaire can be seen that the patients had a superior perception before the procedure. CONCLUSIONS: Patients treated by surgery have a better perception of quality-of-life compared to those treated by radiotherapy.

OBJETIVO: Determinar y comparar los resultados funcionales y de calidad de vida de pacientes con cáncer de próstata tratados con intención curativa durante el año 2015 en nuestro centro. MÉTODO: Se incluyeron 77 pacientes sometidos a prostatectomía radical (PR) o radioterapia externa con terapia de deprivación androgénica (TDA). Se realizaron el Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) tras 3 años de seguimiento y el Cuestionario Español de Calidad de Vida en Pacientes con Cáncer de Próstata (CAVIPRES-30) al diagnóstico y a los 3 años. RESULTADOS: Se incluyeron 68 pacientes, 39 con PR y 29 con radioterapia más TDA. De los pacientes intervenidos, el 61.5% están secos y el 17.9% usan tres o más compresas, diarias frente al 72.4% y el 6.8%, respectivamente, en el grupo de radioterapia. El 48.7% de los prostatectomizados refieren erecciones muy malas o ninguna, frente al 69% de los radiados. Tras la cirugía, el 43.6% refieren mala o muy mala calidad de vida, frente al 68.9% de los radiados. En la comparación de los datos del cuestionario pre- y postratamiento, los pacientes tenían una percepción superior antes del procedimiento. CONCLUSIONES: Los pacientes tratados mediante cirugía tienen una mejor percepción de su calidad de vida relacionada con la salud que los radiados.

Pregnant and recently pregnant women's perceptions about influenza a pandemic (H1N1) 2009: implications for public health and provider communication.

The objective of this study was to explore pregnant and recently pregnant women's perceptions of influenza vaccine and antivirals during the 2009 H1N1 pandemic. We conducted 18 focus groups with pregnant and recently pregnant women in three US cities in September 2009. Participants were segmented into groups by insurance status (no or public insurance vs. private insurance), vaccine attitudes (higher vs. lower likelihood of acceptance of any vaccines, not only influenza vaccines), and parity (first child vs. other children in the home) based on information they provided on the screening questionnaire at the time of recruitment. We found that women are not well informed about influenza vaccinations and antiviral medicine and have significant concerns about taking them during pregnancy. An interest in their infant's well-being, however, can be strong motivation to adopt preventive recommendations, including vaccination. A woman's health care provider is a highly trusted source of information about the 2009 H1N1. Pregnant women have unique communication needs for influenza. Messages directing pregnant women to adopt public health recommendations, particularly for vaccination or prophylactic medication should include a detailed description of the benefits or lack of risk to the fetus and the safety of breastfeeding. Additionally, messages should recognize that pregnant women are taught to be selective about taking medication and provide a clear rationale for why the medicine or vaccine is necessary.

Assessment of Clinical Parameters of Dental Anxiety during Noninvasive Treatments in Dentistry.

Dental anxiety is a matter of interest for the dentist since an anxious patient is a potential source of complications in the dental office. The main objectives of this study are to describe the correlation between dental anxiety levels and the values of physiological parameters related to dental anxiety and to study the evolution of blood pressure and heart rate over time during noninvasive dental treatments, i.e., not requiring local anesthesia. A descriptive, longitudinal, and prospective observational study was designed. The study population consisted of 200 patients who attended a university clinic for dental treatment without local anesthesia. The patients were asked to complete the Corah Dental Anxiety Scale. Afterward, blood pressure and heart rate were measured by means of a digital sphygmomanometer. Blood pressure and heart rate were taken throughout the procedure on four occasions. Most of the patients showed mild dental anxiety (5 [IQR: 3] points on Corah Dental Anxiety Scale). Significant but weak correlations were found between the level of dental anxiety and heart rate (Spearman rho: 0.166 and 0.176; p = 0.019 and 0.013; 3 min before and after treatment, respectively), as well as between the level of dental anxiety and the duration of treatment (Spearman rho: 0.191 3 min; p = 0.007). As for the evolution of physiological parameters, all patients showed a progressive decrease in values at different time points during treatment. When the types of treatment were evaluated separately, it was observed that there were statistically significant differences between them with respect to the level of dental anxiety (p = 0.006).

Peer review of the pesticide risk assessment of the active substance lavandulylsenecioate.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Italy for the pesticide active substance lavandulylsenecioateare reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council.The conclusions were reached on the basis of the evaluation of the representative uses evaluated as a pheromone comprising manual applications to control Planococcusficus (vine mealybug) populations by mating disruption in table grape, wine grape, raisins and any other crops where P. ficus may be a pest in Southern Europe. The reliable endpoints,appropriate for use in regulatory risk assessmentare presented. Missing information identified as being required by the regulatory framework is listed.Concerns are identified.

Involvement of the retinoic acid signaling pathway in sex differentiation and pubertal development in the European sea bass Dicentrarchus labrax.

Retinoic Acid (RA) is a vitamin A derivative present in many biological processes including embryogenesis, organ development and cell differentiation. The RA signaling pathway is essential for the onset of meiosis in tetrapods, although its role in fish reproduction needs further evidence. This study reports the expression profiles of several genes involved in this pathway during sex differentiation and the first reproductive season in European sea bass (Dicentrarchus labrax) gonads. The assessed genes are representative of several steps of the pathway including retinol transport, RA synthesis, nuclear receptors, RA transport and degradation. The study includes a synteny analysis of stra8, a tetrapod meiosis gatekeeper, in several taxa. The results show that, these genes were overexpressed during early gonad development and their expression decreased during meiosis progression in males and during vitellogenesis in females. Specifically, a decrease of cyp26a1, involved in RA degradation, together with an increase of aldh1a2 and aldh1a3, in charge of RA-synthesis, might ensure the availability of high RA levels at the time of meiosis in males and females. Moreover, the absence of stra8 in the European sea bass genome, as well as the conserved genomic neighbourhood found in other taxa, suggest a stra8 independent signaling for RA during meiosis. Taken together, our results might help to better understand the role of RA signaling in teleost gonad development.

Modification of the existing maximum residue levels for tetraconazole in kaki/Japanese persimmon, linseeds and poppy seeds.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Isagro S.p.A submitted a request to the competent national authority in Italy to modify the existing maximum residue levels (MRLs) for the active substance tetraconazole in various crops and animal commodities. The data submitted in support of the request were found to be sufficient to derive MRL proposals for tetraconazole in kaki/Japanese persimmon, linseeds and poppy seeds. Adequate analytical methods for enforcement are available to control MRL compliance for parent compound tetraconazole on the commodities under consideration and in animal products. The proposed use of tetraconazole on crops under assessment will not result in a dietary exposure to residues of parent tetraconazole exceeding the toxicological reference values for tetraconazole. For triazole derivative metabolites (TDMs), only an indicative exposure assessment was performed considering only the crops under assessment; the results showed that the expected exposure to TDMs in the three assessed commodities is well below the toxicological reference values derived for the TDMs. The proposed use of tetraconazole on crops under assessment is therefore unlikely to pose a risk to consumers' health. TDMs may be generated by several pesticides belonging to the group of triazole fungicides, a comprehensive risk assessment has thus to be performed that covers all existing EU uses and import tolerances for all pesticides belonging to the class of triazole fungicides. EFSA recommended to elaborate together with risk managers a strategy to ensure that the required data are made available to finalise the overall risk assessment for triazole fungicides.

Modification of the existing maximum residue level for cyprodinil in Florence fennel.

In accordance with Article 6 of Regulation (EC) No 396/2005, the FPS Health, Food chain safety and Environment of Belgium, submitted an application to modify the existing maximum residue level (MRL) for the active substance cyprodinil in Florence fennel to accommodate the intended use in the northern Europe. The submitted data were found sufficient to derive an MRL proposal of 4 mg/kg for cyprodinil in Florence fennel. Adequate analytical methods for enforcement are available to control the residues of cyprodinil in the plant matrix under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the long-term intake of residues resulting from the authorised uses of cyprodinil and the intended use on Florence fennel is unlikely to present a risk to consumer health. An indicative acute exposure assessment was performed, considering the acute reference dose (ARfD) proposed by the rapporteur Member State (RMS) in the framework of the currently ongoing renewal of the approval of cyprodinil; no acute health concerns were identified with regard to cyprodinil residues in Florence fennel. As the peer review on the renewal of the approval of cyprodinil in accordance with Regulation (EC) No 1107/2009 is currently ongoing, the conclusions reported in this reasoned opinion may need to be reconsidered in the light of the outcome of the peer review.

Modification of the existing maximum residue level for fluopyram in broccoli.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer Hellas AG submitted a request to the competent national authority in Greece to modify the existing maximum residue level (MRL) for the active substance fluopyram in broccoli. The data submitted in support of the request were found to be sufficient to derive MRL proposals for broccoli. Adequate analytical methods for enforcement are available to control the residues of fluopyram on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of fluopyram according to the reported agricultural practice for broccoli will not result in consumer exposure exceeding the toxicological reference values and therefore are unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for pyridaben in tomatoes and aubergines.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Nissan Chemical Europe S.A.S. submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance pyridaben in tomatoes and aubergines. An MRL proposal of 0.15 mg/kg was derived for tomatoes and aubergines which reflects the intended use of the plant protection product containing pyridaben. Adequate analytical methods for enforcement are available to control the residues of pyridaben in plant matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concludes that the proposed use of pyridaben on tomatoes and aubergines will not result in a consumer exposure exceeding the toxicological reference values and therefore it is unlikely to pose a risk to consumers' health.

Reporting data on pesticide residues in food and feed according to Regulation (EC) No 396/2005 (2018 data collection).

According to Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed, Member States have to monitor pesticide residue levels in food samples and submit the monitoring results to EFSA and the European Commission. The Standard Sample Description (SSD, version 1) is the data model used for reporting the data on analytical measurements of chemical substances occurring in food, feed and water to EFSA. This document is a consolidated version of the past four years' guidance defining the appropriate SSD codes to describe the samples and the analytical results and it gives directions for the reporting of the pesticide residues monitoring data starting with the data generated in 2018 onwards. These provisions take into account the experience of both the previous reporting seasons and the new legislation applicable in 2018. This EFSA Guidance will not be applicable for the 2019 data collection provided to EFSA in 2020. In 2020, all data on annual monitoring will be transmitted in SSD2 format only.

Modification of the existing maximum residue level for fludioxonil in Florence fennels.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Belgium Federal Public Service for Health, Food chain safety and Environment (Belgium FPS Health) submitted a request to modify the existing maximum residue level (MRL) for the active substance fludioxonil in Florence fennels. The data submitted in support of the request were found to be sufficient to derive an MRL proposal of 1.5 mg/kg for Florence fennels. Adequate analytical methods for enforcement are available to control the residues of fludioxonil on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the long-term intake of residues resulting from the use of fludioxonil according to the reported agricultural practice is unlikely to present a risk to consumer health.

Evaluation of confirmatory data following the Article 12 MRL review for bentazone.

The applicant BASF SE submitted a request to the competent national authority in the Netherlands to evaluate the confirmatory data that were identified for bentazone in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, a new livestock feeding study and storage stability data for bentazone and 6-hydroxy bentazone in animal matrices were submitted. To address the data gap for potatoes, adjusted less critical good agricultural practices (GAPs) were reported and supporting residue data were provided. The data gap related to analytical methods in fat and herbal infusions were addressed in the framework of the peer review. The data gap for residue trials on leek has not been addressed. Further confirmation from the applicant/Member States are needed for the clarification of the GAP for herbal infusions. Based on the information submitted in support of the confirmatory data request, the existing EU MRLs for bentazone need to be modified for potato and leek, for swine fat and kidney and for bovine, equine, goat and sheep fat, liver and milk. The consumer risk assessment performed in the MRL review was updated, using new toxicological reference values derived by the peer review. No consumer intake concerns were identified.

Modification of the existing maximum residue level for acibenzolar-S-methyl in hazelnuts.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Syngenta France SAS submitted a request to the competent national authority in France to modify the existing maximum residue level (MRL) for the active substance acibenzolar-S-methyl in hazelnuts. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for hazelnuts/cobnuts. Adequate analytical methods for enforcement are available to control residues of acibenzolar-S-methyl in the plant matrix under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of acibenzolar-S-methyl according to the reported agricultural practice is unlikely to present a risk to consumer health.

Review of the existing maximum residue levels for triazoxide according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance triazoxide. To assess the occurrence of triazoxide residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008, as well as the European authorisations reported by Member States. Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. All information required by the regulatory framework was present and a risk to consumers was not identified.

Review of the existing maximum residue levels for chromafenozide according to Article 12 Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance chromafenozide. Considering the information provided by Member States, neither EU uses nor import tolerances are currently authorised for chromafenozide within the EU. Furthermore, no MRLs are established by the Codex Alimentarius Commission (codex maximum residue limits) for this active substance. Therefore, residues of chromafenozide are not expected to occur in any plant or animal commodity and therefore a consumer risk assessment is not required. Nevertheless, the available information allowed EFSA to propose a marker residue definition and a limit of quantification (LOQ) for enforcement against potential illegal uses.

Modification of the existing maximum residue levels for aminopyralid in certain cereals.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Dow AgroSciences Denmark submitted a request to the competent national authority in the United Kingdom to modify the existing maximum residue levels (MRLs) for the active substance aminopyralid in cereals. The data submitted in support of the request were found to be sufficient to derive MRL proposals for barley, rye, sorghum, millet and oats. A modification of the existing MRL of aminopyralid in wheat has been considered unnecessary. Adequate analytical methods for enforcement are available to control the residues of aminopyralid and its conjugates in plant matrices and on the commodities under assessment at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of aminopyralid according to the intended agricultural practices is unlikely to present a risk to consumer health.