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The circadian clock is an internal molecular oscillator and coordinates numerous physiological processes through regulation of molecular pathways. Tissue-specific clocks connected by mobile signals have previously been found to run at different speeds in

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Resumen La Seccion de Via Aerea de la Sociedad Catalana de Anestesiologia, Reanimacion y Terapeutica del Dolor (SCARTD) presenta la actualizacion de las recomendaciones para la evaluacion y manejo de la via aerea dificil con el fin de incorporar los avances tecnicos y los cambios observados en la practica clinica desde la publicacion de la primera edicion en 2008. La metodologia elegida fue la adaptacion de 5 guias internacionales recientemente publicadas, cuyo contenido fue previamente analizado y comparado de forma estructurada, y el consenso de expertos de los 19 centros participantes. El documento final fue sometido a la valoracion de los miembros de la SCARTD y a la revision por parte de 11 expertos independientes. Estas recomendaciones estan pues sustentadas en la evidencia cientifica actualmente disponible y en un amplio acuerdo de los profesionales de su ambito de aplicacion. En esta edicion se amplia la definicion de via aerea dificil, abarcando todas las tecnicas de manejo, y se hace mayor hincapie en la valoracion de la via aerea y en la clasificacion en 3 categorias segun el potencial grado de dificultad y las consideraciones de seguridad adicionales, que guiaran la planificacion de la estrategia a seguir. La preparacion previa al manejo de la via aerea, no solo relativa al paciente y al material, sino tambien a la comunicacion e interaccion entre todos los agentes implicados, ocupa un lugar destacado en todos los escenarios incluidos en el presente documento. El texto refleja el aumento progresivo del uso de los videolaringoscopios y de los dispositivos de segunda generacion en nuestro entorno y promueve tanto su uso electivo como el uso precoz en la via aerea no prevista. Tambien recoge la creciente utilizacion de la ecografia como herramienta de apoyo en la exploracion y toma de decisiones. Se han abordado nuevos escenarios como el riesgo de broncoaspiracion y la extubacion considerada dificil. Finalmente, se trazan las lineas maestras de los programas de entrenamiento y formacion continuada en via aerea necesarios para garantizar la implementacion efectiva y segura de las recomendaciones.

The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines.

Circadian clocks allow organisms to anticipate environmental changes associated with the diurnal light/dark cycle. Circadian oscillators have been described in plants and green algae, cyanobacteria, animals and fungi, however, little is known about the circadian clocks of photosynthetic eukaryotes outside the green lineage. Stramenopiles are a diverse group of secondary endosymbionts whose plastid originated from a red alga. Photosynthetic stramenopiles, which include diatoms and brown algae, play key roles in biogeochemical cycles and are important components of marine ecosystems. Genome annotation efforts indicated the presence of a novel type of oscillator in these organisms and the first circadian clock component in a stramenopile has been recently discovered. This review summarizes the phenotypic characterization of circadian rhythms in stramenopiles and current efforts to determine the mechanisms of this 'brown clock'. The elucidation of this brown clock will enable a deeper understanding of the role of self-sustained oscillations in the adaptation to life in marine environments.

Bisphenol A (BPA) is one of the main ubiquitous compounds released from plastics in the environment. This compound, considered an endocrine disruptor, poses a risk to aquatic wildlife and human population, being included in multiple environmental monitoring programmes. Following the regulations restricting BPA use in the last years, BPA-like chemicals have been produced and used as BPA substitutes. However, they are not commonly included in monitoring programs yet and their presence is thus misrepresented, despite showing similar endocrine disrupting potential. In this work, an analytical method for analysing bisphenol A and five of its analogues (Bisphenol S, B, F, AF and Tetrabromobisphenol A) is described, validated for water (riverine, sea and wastewater), sediment, and biota (fish and biofilm) and applied to monitor their presence in the Ebro River Delta (NE Spain). In addition, plastic litter was also collected to evaluate their role as potential source of bisphenols. All compounds except BPF were detected in the analysed samples. Wastewater treatment plants (WWTPs) were discarded as major sources of BPs into the natural aquatic environment, as no BPs were detected in treated effluents. Indeed, the high levels of BPs in the natural environment could be related with direct discharge of raw wastewater from small rural population nucleus. The analysis of riverine plastic leachates yielded 4 out of the 6 BPs analysed, strengthening the hypothesis that plastic debris are also a source of BPs in the natural environment. Whereas Bisphenol S and BPA were detected in water and, to a limited extent, in biota, less polar analogues (mainly BPAF and TBBPA) were not found in any of the water samples. Instead, these hydrophobic BPs were found in fish tissues and biofilm, pointing out plastics and microplastics as their possible vectors. Finally, biofilm demonstrated its potential as sentinel of chemical contamination in freshwater environment., Authors acknowledge Spanish Ministry of Economy and Competitiveness (project PLAS-MED; CTM2017-89701-C3-2-R) for its financial support. Authors acknowledge Maria Guzman for her support in the sample analysis and method development. J.M. Castaño-Ortiz acknowledges the predoctoral grant from the Agency for Management of University and Research Grants (AGAUR) (2019 FI_B 00881). R. Muñoz-Mas benefitted from a postdoctoral Juan de la Cierva fellowship from the Spanish Ministry of Science (FJCI-2016-30829).

The extent of the widespread, planetary contamination by plastic waste is difficult to fully capture. Nanoplastics (NPs) are currently in the center of research concerning plastic litter, both for the analytical challenges they pose and for their potential to provoke hazardous effects in organisms. However, there are still many unanswered questions in this multidisciplinary field, with a crucial missing piece being the quantification of NPs in fish tissues after in vivo exposures. Another relevant question that is still greatly unexplored is how a chronic exposure to NPs will affect fish health. This study aims to provide answers to both of these relevant knowledge gaps. To this end, goldfish (Carassius auratus) were exposed to 44 nm polystyrene (PS)-NPs via water for 30 days. Following the exposure, gastrointestinal tract, liver and muscle were sampled for PS-NPs analysis by means of size exclusion chromatography coupled to high resolution mass spectrometry. PS-NPs were detected in all liver and muscle samples of exposed fish, with higher concentrations in liver than in muscle, whereas no PS-NPs were detected in the gastrointestinal tract. Nevertheless, exposure to PS-NPs did not induce changes in hematology parameters nor in cortisol and glucose levels in plasma. On the other hand, even a relatively low concentration of PS-NPs was able to cause DNA damage, measured by an increase in erythrocyte nuclear abnormalities, suggesting that PS-NPs can reach the cell nucleus and cause genotoxicity. These results show for the first time that PS-NPs find their way to fish muscle after chronic exposure, where they bioaccumulate, but do not alter fish survival nor hematological or physiological stress indicators. The accumulation of PS-NPs in fish muscle can represent a threat to human health as a possible route of exposure to small-sized plastics. The present results in a model fish species open windows for future studies in edible fish species., This research was supported through Plan Nacional de Investigación with reference PID 2020-113221RB-I00 and through the project with reference PLAS-MED; CTM 2017-89701-C3-2-R. MT is supported by a Ramon y Cajal contract (ref. RYC 2019-026841-I) and IB is supported by a PhD grant from Generalitat de Catalunya (2018FI_B_00711). ML acknowledges DEGBIOPLAST (RTI 2018-097860-J-I00) and AV his PhD grant PRE 2018-083989, both from the Spanish Ministry of Science and Innovation.

Nannochloropsis oceanica, like other stramenopile microalgae, is rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA). We observed that fatty acid desaturases (FADs) involved in LC-PUFA biosynthesis were among the strongest blue light-induced genes in N. oceanica CCMP1779. Blue light was also necessary for maintaining LC-PUFA levels in CCMP1779 cells, and growth under red light led to a reduction in EPA content. Aureochromes are stramenopile-specific proteins that contain a light–oxygen–voltage (LOV)-sensing domain that associates with a flavin mononucleotide and is able to sense blue light. These proteins also contain a basic leucine zipper DNA-binding motif and can act as blue light-regulated transcription factors by associating with an E-box like motif, which we found enriched in the promoters of blue light-induced genes. We demonstrated that, in vitro, two CCMP1779 aureochromes were able to absorb blue light. Moreover, the loss or reduction of the expression of any of the three aureochrome genes led to a decrease in the blue light-specific induction of several FADs in CCMP1779. EPA content was also significantly reduced in NoAUREO2 and NoAUREO4 mutants. Taken together, our results indicate that aureochromes mediate blue light-dependent regulation of LC-PUFA content in N. oceanica CCMP1779 cells.

The marine microalgae Nannochloropsis oceanica (CCMP1779) is a prolific producer of oil and is considered a viable and sustainable resource for biofuel feedstocks. Nitrogen (N) availability has a strong impact on the physiological status and metabolism of microalgal cells, but the exact nature of this response is poorly understood. To fill this gap we performed transcriptomic profiling combined with cellular and molecular analyses of N. oceanica CCMP1779 during the transition from quiescence to autotrophy. N deprivation-induced quiescence was accompanied by a strong reorganization of the photosynthetic apparatus and changes in the lipid homeostasis, leading to accumulation of triacylglycerol. Cell cycle activation and re-establishment of photosynthetic activity observed in response to resupply of the growth medium with N were accompanied by a rapid degradation of triacylglycerol stored in lipid droplets (LDs). Besides observing LD translocation into vacuoles, we also provide evidence for direct interaction between the LD surface protein (NoLDSP) and AUTOPHAGY-RELATED8 (NoATG8) protein and show a role of microlipophagy in LD turnover in N. oceanica CCMP1779. This knowledge is crucial not only for understanding the fundamental mechanisms controlling the cellular energy homeostasis in microalgal cells but also for development of efficient strategies to achieve higher algal biomass and better microalgal lipid productivity.

SummaryCircadian clocks allow organisms to predict environmental changes caused by the rotation of the Earth. Although circadian rhythms are widespread among different taxa, the core components of circadian oscillators are not conserved and differ between bacteria, plants, animals and fungi. Stramenopiles are a large group of organisms in which circadian rhythms have been only poorly characterized and no clock components have been identified. We have investigated cell division and molecular rhythms inNannochloropsisspecies. In the four strains tested, cell division occurred principally during the night period under diel conditions, however, rhythms dampened within 2-3 days after transfer to constant light. We developed firefly luciferase reporters for long-term monitoring ofin vivotranscriptional rhythms in twoNannochlropsisspecies,N. oceanicaCCMP1779 andN. salinaCCMP537. The reporter lines express free-running bioluminescence rhythms with periods of ~21-31 h that dampen within ~3-4 days under constant light. Using different entrainment regimes, we demonstrate that these rhythms are regulated by a circadian-type oscillator. In addition, the phase of free-running luminescence rhythms can be modulated pharmacologically using a CK1 ε/δ inhibitor, suggesting a role of this kinase in theNannochloropsisclock. Together with the molecular and genomic tools available forNannochloropsisspecies, these reporter lines represent an excellent system for future studies on the molecular mechanisms of stramenopile circadian oscillators.Significance statementStramenopiles are a large and diverse line of eukaryotes in which circadian rhythms have been only poorly characterized and no clock components have been identified. We have developed bioluminescence reporter lines inNannochloropsisspecies and provide evidence for the presence of a circadian oscillator in stramenopiles; these lines will serve as tools for future studies to uncover the molecular mechanisms of circadian oscillations in these species.

Nannochloropsis oceanica, as other stramenopile microalgae, is rich in long-chain polyunsaturated fatty acids (LC-PUFA) such as eiconsapentaenoic acid (EPA). We observed that fatty acid desaturases (FAD) involved in LC-PUFA biosynthesis were among the strongest blue light induced genes in N. oceanica CCMP1779. Blue light was also necessary for maintaining LC-PUFA levels in CCMP1779 cells, and growth under red light led to a reduction in EPA content. Aureochromes are stramenopile specific proteins that contain a light-oxygen-voltage-sensing (LOV) domain that associates with a flavin mononucleotide and is able to sense blue light. These proteins also contain a bZIP DNA binding motif and can act as blue light regulated transcription factors by associating with a E-box like motif, which we found enriched in the promoters of blue light induced genes. We demonstrated that, in vitro, two CCMP1779 aureochromes were able to absorb blue light. Moreover, the loss or reduction of any of the three aureochromes led to a decrease in the blue light specific induction of several FADs in CCMP1779. EPA content was also significantly reduced in NoAureo 2 and NoAureo 4 mutants. Taken together, our results indicate that aureochromes mediate blue light dependent regulation of LC-PUFA content in N. oceanica CCMP1779 cells.

We deal with the construction of linear connections associated with second order ordinary differential equations with and without first order constraints. We use a novel method allowing glueing of submodule covariant derivatives to produce new, closed form expressions for the Massa-Pagani connection and our extension of it to the constrained case., GP and MFP thank Instituto de Ciencias Matemáticas (ICMAT) for its warm hospitality. MFP acknowledges financial support from the FWO (Research Foundation - Flanders) under grant 1282021N. DMdD acknowledges financial support from the Spanish Ministry of Science and Innovation, under grants PID2019-106715GB-C21 and the Spanish National Research Council, through the ?Ayuda extraordinaria a Centros de Excelencia Severo Ochoa? R&D (CEX2019-000904-S).

International audience; Nannochloropsis species, unicellular industrial oleaginous microalgae, are model organisms for microalgal systems and synthetic biology. To facilitate community-based annotation and mining of the rapidly accumulating functional genomics resources, we have initiated an international consortium and present a comprehensive multi-omics resource database named Nannochloropsis Design and Synthesis (NanDeSyn; http://nandesyn.single-cell.cn). Via the Tripal toolkit, it features user-friendly interfaces hosting genomic resources with gene annotations and transcriptomic and proteomic data for six Nannochloropsis species, including two updated genomes of Nannochloropsis oceanica IMET1 and Nannochloropsis salina CCMP1776. Toolboxes for search, Blast, synteny view, enrichment analysis, metabolic pathway analysis, a genome browser, etc. are also included. In addition, functional validation of genes is indicated based on phenotypes of mutants and relevant bibliography. Furthermore, epigenomic resources are also incorporated, especially for sequencing of small RNAs including microRNAs and circular RNAs. Such comprehensive and integrated landscapes of Nannochloropsis genomics and epigenomics will promote and accelerate community efforts in systems and synthetic biology of these industrially important microalgae.

(1) Background: The Differential Susceptibility to Media Effects Model (DSMM) suggests that pornography use effects are conditional and they depend on dispositional, developmental, and social differential susceptibility variables. This framework also highlights that the differential susceptibility variables act as predictors of pornography use and as moderators of the effect of pornography on criterion variables. (2) Methods: By administering a survey to n = 1500 adolescents, we tested whether these assumptions were met. (3) Results: Pornography use was related to being male and older, having a bisexual or undefined sexual orientation, higher substance use, being non-Muslim, and reporting sexual interest and the use of the media to obtain sexual information. Structural Equation Modeling (SEM) showed that higher levels in the criterion variables were directly related to pornography use, older age, substance use, and being women. Some mediational links also emerged. Pornography use mediated between the age and criterion variables. Moreover, substance use mediated the association between age and gender with the criterion variables. (4) Conclusions: Our findings support the clinical applicability of the theoretical DSMM framework. Knowing adolescent pornography consumers’ profiles and the impact of pornography on this population would allow for the designing of more effective prevention and regulation proposals.

(1) Background: Female genital mutilation/cutting (FGM/C) is associated with physical and psychological complications. However, there is scarce literature on how women with FGM/C respond to treatment interventions. (2) Methods: In the present pilot longitudinal study, we assessed changes in general psychopathology (Symptom Check List-90-R), sexual functioning and distress (Female Sexual Function Index, Female Sexual Distress Scale-Revised, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) female sexual dysfunction criteria), body image (Body Shape Questionnaire), and sexual body image (Female Genital Self-Image Scale) in a sample of n = 15 women with FGM/C before and after reconstructive surgery. (3) Results: Sexual distress was significantly improved following surgery. We also observed an improvement in general psychopathology and genital self-image. However, sexual function was not improved. (4) Conclusions: These results provide evidence for the benefits of reconstructive surgery on sexual distress in women with FGM/C. The impact of surgery on sexual function cannot be conclusively evaluated.

Sexual activity offers numerous advantages for physical and mental health but maintains inherent risks in a pandemic situation, such as the current one caused by SARS-CoV-2. A group of experts from the Spanish Association of Sexuality and Mental Health (AESexSAME) has reached a consensus on recommendations to maintain lower-risk sexual activity, depending on one’s clinical and partner situations, based on the current knowledge of SARS-CoV-2. Different situations are included in the recommendations: a sexual partner passing quarantine without any symptoms, a sexual partner that has not passed quarantine, a sexual partner with some suspicious symptoms of COVID-19, a positive sexual partner with COVID-19, a pregnant sexual partner, a health professional partner in contact with COVID-19 patients, and people without a sexual partner. The main recommendations include returning to engaging in safe sex after quarantine is over (28 days based on the duration one can carry SARS-CoV-2, or 33 days for those who are >60 years old) and all parties are asymptomatic. In all other cases (for those under quarantine, those with some clinical symptoms, health professionals in contact with COVID-19 patients, and during pregnancy), abstaining from coital/oral/anal sex, substituting it with masturbatory or virtual sexual activity to provide maximum protection from the contagion, and increasing the benefits inherent to sexual activity are recommended. For persons without a partner, not initiating sexual activity with a sporadic partner is strongly recommended.

Natural light environments are highly variable. Flexible adjustment between light energy utilization and photoprotection is therefore of vital importance for plant performance and fitness in the field. Short-term reactions to changing light intensity are triggered inside chloroplasts and leaves within seconds to minutes, whereas long-term adjustments proceed over hours and days, integrating multiple signals. While the mechanisms of long-term acclimation to light intensity have been studied by changing constant growth light intensity during the day, responses to fluctuating growth light intensity have rarely been inspected in detail. We performed transcriptome profiling in Arabidopsis (Arabidopsis thaliana) leaves to investigate long-term gene expression responses to fluctuating light (FL). In particular, we examined whether responses differ between young and mature leaves or between morning and the end of the day. Our results highlight global reprogramming of gene expression under FL, including that of genes related to photoprotection, photosynthesis, and photorespiration and to pigment, prenylquinone, and vitamin metabolism. The FL-induced changes in gene expression varied between young and mature leaves at the same time point and between the same leaves in the morning and at the end of the day, indicating interactions of FL acclimation with leaf development stage and time of day. Only 46 genes were up- or down-regulated in both young and mature leaves at both time points. Combined analyses of gene coexpression and cis-elements pointed to a role of the circadian clock and light in coordinating the acclimatory responses of functionally related genes. Our results also suggest a possible cross talk between FL acclimation and systemic acquired resistance-like gene expression in young leaves.

Background: Female genital mutilation/cutting (FGM/C) links health complications and psychological distress. However, there is scarce literature on how women with FGM/C respond to treatment interventions. Objective: In this study, we aimed to assess changes in depression symptomatology, sexual function, and distress following clitoral reconstructive surgery combined with a psychoeducational intervention. Methods: The reconstructive surgery consisted of recovering the remaining clitoris and placing it externally and as close to the vagina as possible. FGM/C patients (n = 27) received psychological support and sexual counseling upon undergoing the surgical intervention and were further assessed at 6-month follow-up. Moreover, they completed the Beck Depression Inventory and the Female Sexual Distress Scale Revised at these two time points. Patients’ sexual dysfunction was assessed according to DSM-5 criteria. Results: Statistically significant clinical changes after FGM/C were reported. Overall, pat...

Nannochloropsis oceanica is an oleaginous microalga rich in ω3long-chain polyunsaturated fatty acids (LC-PUFAs) content, in the form of eicosapentaenoic acid (EPA). We identified the enzymes involved in LC-PUFA biosynthesis in N. oceanica CCMP1779 and generated multigene expression vectors aiming at increasing LC-PUFA content in vivo. We isolated the cDNAs encoding four fatty acid desaturases (FAD) and determined their function by heterologous expression in S. cerevisiae. To increase the expression of multiple fatty acid desaturases in N. oceanica CCMP1779 we developed a genetic engineering toolkit that includes an endogenous bidirectional promoter and optimized peptide bond skipping 2A peptides. The toolkit also includes multiple epitopes for tagged fusion protein production and two antibiotic resistance genes. We applied this toolkit, towards building a gene stacking system for N. oceanica that consists of two vector series, pNOC-OX and pNOC-stacked. These tools for genetic engineering were employed to test the effects of the overproduction of one, two or three desaturase encoding cDNAs in N. oceanica CCMP1779 and prove the feasibility of gene stacking in this genetically tractable oleaginous microalga. All FAD overexpressing lines had considerable increases in the proportion of LC-PUFAs, with the overexpression of Δ12 and Δ5 FAD encoding sequences leading to an increase in the final ω3 product, EPA. This article is protected by copyright. All rights reserved.

Introduction/Background The survival rates improvement of oncogynecologic surgeries and adjuvant therapies has led to focus on their long-term effects. Lower tract urinary symptoms (LTUS), sexual dysfunction (SD) and impaired quality of life (QoL) have been described as common complications in survivors. Disruption of paracervical autonomic fibers during hysterectomy and radiation cystitis could be main LTUS causes; while psycho-affective deterioration may play great role on SD. Our aim was to assess changes on these aspects after oncogynecological radical treatment. Methodology This prospective cohort study included oncogynecological patients (endometrial, cervical and ovarian) undergoing radical-intent treatment in our unit, March2017-June2018, classified according the received therapy. ERAS protocol (Enhanced Recovery after Surgery) was performed. Baseline features as age, surgical-obstetric history, comorbidities, emotional traits and relationship stability were considered. All patients were surveyed before and 6 months after treatment, using validated questionnaires: ICIQ-UI-SF (International-Consultation-Incontinence-Questionnaire) evaluating LTUS impact on QoL, CACV (‘Cuestionario-de-Autoevaluacion-de-Control-Vesical’) for detrusor dysfunction, ISFS (Index-of-Feminine-Sexual-Function) measuring SD risk, and SF-12 providing QoL profile. Results 67 patients were finally included, without finding differences in baseline characteristics among the 46 ones completing both surveys and analysed. Pre-treatment, 50.7% patients reported urinary incontinence (UI), 74.6% no sexual activity and all high QoL scores. In the follow-up, an UI worsening tendency with advanced age was found independently of treatment modality, not reaching statistical significance. Mental QoL score in SF-12 reduced ∼2.5 points if undergoing radiotherapy. SD did not differ from pre-treatment status. Conclusion Urinary and sexual function, as global QoL, remained stable 6 months after oncogynecological treatment. Although LTUS is difficult to assess being common in gynecological patients baseline, special attention is recommended in older women to avoid UI worsening. Those receiving radiotherapy may benefit from mental QoL support. Further research with larger populations is needed to accurately assess the impact of radical oncogynecological treatments; probably leading to develop patient-targeted recovery programs. Disclosure The authors declare no conflicts of interest. None received grant support for this study neither for other clinical or research activity, except for the inscription to the current congress for 3 authors that was funded by VIFOR Pharma (non related to the study we present).

espanolObjetivo: identificar las reacciones de los cuidadores familiares de pacientes con demencia en el cuidado que realizan en el ambito domiciliario frente al cuidado efectuado en el ambito de institucionalizacion de larga estancia; y estudiar la evolucion en tres meses. Metodo: estudio analitico observacional de cohorte prospectivo en pacientes con demencia y sus cuidadores familiares (n= 287) que viven en su domicilio (PDD) o en centros de larga estancia, (PDI) que respondieron al cuestionario validado Caregiver Reaction Assessment (CRA). Tratamiento estadistico: prueba t para muestras repetidas, prueba t para muestras independientes y prueba de signos de Wilcoxon. Este estudio forma parte del proyecto europeo RightTimePlaceCare (RTPC). Resultados: se incluyeron 241 cuidadores familiares de PDD (n= 155) y de PDI (n= 86). En las subescalas de CRA en basal, en el grupo PDD tenian menos apoyo por parte de las familias (11 vs. 13; p= 0,006), mayores interferencias en las actividades de la vida diaria por el hecho de cuidar (16 vs. 18; p= 0,020), y consideraban una menor influencia de cuidar en sus finanzas comparado con el grupo PDI (10 vs. 7; p Conclusion: en las reacciones de quienes cuidan de pacientes con demencia, el impacto mas acentuado se produce en las interferencias de la vida diaria de los cuidadores domiciliarios y a los tres meses de seguimiento hay una mejora en esta dimension. Ademas, cuando el paciente con demencia esta institucionalizado el cuidador tiene mayor apoyo familiar. Estos resultados dan claves para que profesionales sanitarios enfoquen los cuidados dirigidos a la salud fisica, psiquica y social de los cuidadores. EnglishObjective: to identify the reactions of family caregivers for patients with dementia regarding their care in the home setting vs. care conducted in the long-term institutionalized setting; and to study their evolution at 3 months. Method: a prospective analytical observational cohort study in patients with dementia and their family caregivers (n= 287) who live at home (PDD) or in long-stay centers (PDI), and who answered the validated questionnaire Caregiver Reaction Assessment (CRA). Statistical treatment: t test for paired samples, t test for independent samples, and Wilcoxon signed-rank test. This study is part of the European project RightTimePlaceCare (RTPC). Results: the study included 241 family caregivers of PDD (n= 155) and PDI (n= 86). In the CRA sub-scales at baseline, those in the PDD arm had less support by their families (11 vs. 13; p= 0.006), higher interference in daily life activities (DLA) due to their caregiving (16 vs. 18; p= 0.020), and they considered there was a lower impact of care on their economy vs. the PDI arm (10 vs. 7; p Conclusion: in terms of the reactions of those who care for dementia patients, the highest impact occurs in daily life interferences for home caregivers, and at 3 months of follow-up there is an improvement in this dimension. Moreover, when the patient with dementia becomes institutionalized, there is higher family support for the caregiver. These results provide the keys for healthcare professionals to focus their care on the physical, psychological and social health of caregivers.

Body dissatisfaction is a relevant aspect in both eating disorders and sexuality. Using Stice’s model, this study aimed to evaluate the relationship between these variables in eating disorder patients compared with healthy controls. Statistically significant correlations between body dissatisfaction and sexuality were found in the whole sample. The clinical group had higher rates of body dissatisfaction and sexual impairment. Within the clinical group, the participants with a greater drive for thinness showed higher sexual dysfunctions. These results suggest that sexuality should be systematically explored in eating disorders. Higher rates of drive for thinness may be associated with greater sexual impairment.

Rationale & Objective Clinical practice guidelines for dietary intake in hemodialysis focus on individual nutrients. Little is known about associations of dietary patterns with survival. We evaluated the associations of dietary patterns with cardiovascular and all-cause mortality among adults treated by hemodialysis. Study Design Prospective cohort study. Setting & Participants 8,110 of 9,757 consecutive adults on hemodialysis (January 2014 to June 2017) treated in a multinational private dialysis network and with analyzable dietary data. Exposures Data-driven dietary patterns based on the GA2LEN food frequency questionnaire. Participants received a score for each identified pattern, with higher scores indicating closer resemblance of their diet to the identified pattern. Quartiles of standardized pattern scores were used as primary exposures. Outcomes Cardiovascular and all-cause mortality. Analytical Approach Principal components analysis with varimax rotation to identify common dietary patterns. Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between dietary pattern scores and mortality. Associations were expressed as adjusted HRs with 95% CIs, using the lowest quartile score as reference. Results During a median follow-up of 2.7 years (18,666 person-years), there were 2,087 deaths (958 cardiovascular). 2 dietary patterns, “fruit and vegetable” and “Western,” were identified. For the fruit and vegetable dietary pattern score, adjusted HRs, in ascending quartiles, were 0.94 (95% CI, 0.76-1.15), 0.83 (95% CI, 0.66-1.06), and 0.91 (95% CI, 0.69-1.21) for cardiovascular mortality and 0.95 (95% CI, 0.83-1.09), 0.84 (95% CI, 0.71-0.99), and 0.87 (95% CI, 0.72-1.05) for all-cause mortality. For the Western dietary pattern score, the corresponding estimates were 1.10 (95% CI, 0.90-1.35), 1.11 (95% CI, 0.87-1.41), and 1.09 (95% CI, 0.80-1.49) for cardiovascular mortality and 1.01 (95% CI, 0.88-1.16), 1.00 (95% CI, 0.85-1.18), and 1.14 (95% CI, 0.93-1.41) for all-cause mortality. Limitations Self-reported food frequency questionnaire, data-driven approach. Conclusions These findings did not confirm an association between mortality among patients receiving long-term hemodialysis and the extent to which dietary patterns were either high in fruit and vegetables or consistent with a Western diet.

Huang et al. (1) argue that variant calling methods less conservative than GATK’s Best Practices workflow (2) increased false-positive variant discovery in our study of wild and cultivated potatoes (3), impacting diversity estimates. We disagree with their conclusion and highlight the rationale for the variant calling methods used in our study. First, GATK Best Practices, developed at the Broad Institute, were specifically designed and optimized for human genomics and medical research. Variant calling methodology for human medical research utilizes parameters and validation thresholds not intended for universal application across genomic studies. GATK’s hard filter is openly presented as a bias-prone substitute to their preferred (human-specific) variant quality … [↵][1]1To whom correspondence should be addressed. Email: buell{at}msu.edu. [1]: #xref-corresp-1-1

PSEUDO-RESPONSE REGULATORs (PRRs) play overlapping and distinct roles in maintaining circadian rhythms and regulating diverse biological processes, including the photoperiodic control of flowering, growth, and abiotic stress responses. PRRs act as transcriptional repressors and associate with chromatin via their conserved C-terminal CCT (CONSTANS, CONSTANS-like, and TIMING OF CAB EXPRESSION 1 [TOC1/PRR1]) domains by a still-poorly understood mechanism. Here, we identified genome-wide targets of PRR9 using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and compared them with PRR7, PRR5, and TOC1/PRR1 ChIP-seq data. We found that PRR binding sites are located within genomic regions of low nucleosome occupancy and high DNase I hypersensitivity. Moreover, conserved noncoding regions among Brassicaceae species are enriched around PRR binding sites, indicating that PRRs associate with functionally relevant cis-regulatory regions. The PRRs shared a significant number of binding regions, and our results indicate that they coordinately restrict the expression of target genes to around dawn. A G-box-like motif was overrepresented at PRR binding regions, and we showed that this motif is necessary for mediating transcriptional regulation of CIRCADIAN CLOCK ASSOCIATED 1 and PRR9 by the PRRs. Our results further our understanding of how PRRs target specific promoters and provide an extensive resource for studying circadian regulatory networks in plants.

Circadian clocks allow organisms to predict environmental changes caused by the rotation of the Earth. Although circadian rhythms are widespread among different taxa, the core components of circadian oscillators are not conserved and differ between bacteria, plants, animals and fungi. Stramenopiles are a large group of organisms in which circadian rhythms have been only poorly characterized and no clock components have been identified. We have investigated cell division and molecular rhythms in Nannochloropsis species. In the four strains tested, cell division occurred principally during the night period under diel conditions; however, these rhythms damped within 2-3 days after transfer to constant light. We developed firefly luciferase reporters for the long-term monitoring of in vivo transcriptional rhythms in two Nannochlropsis species, Nannochloropsis oceanica CCMP1779 and Nannochloropsis salina CCMP537. The reporter lines express anticipatory behavior under light/dark cycles and free-running bioluminescence rhythms with periods of ~21-31 h that damped within ~3-4 days under constant light. Using different entrainment regimes, we demonstrate that these rhythms are modulated by a circadian-type oscillator. In addition, the phase of free-running luminescence rhythms can be modulated pharmacologically using a CK1 ε/δ inhibitor, suggesting a role of this kinase in the Nannochloropsis clock. Together with the molecular and genomic tools available for Nannochloropsis species, these reporter lines represent an excellent system for future studies on the molecular mechanisms of stramenopile circadian oscillators.

Objective Recently, the DSM-5 has developed a new diagnostic category named "Substance-related and Addictive Disorders". This category includes gambling disorder (GD) as the sole behavioral addiction, but does not include sex addiction (SA). The aim of this study is to investigate whether SA should be classified more closely to other behavioral addictions, via a comparison of the personality characteristics and comorbid psychopathology of individuals with SA with those of individuals with GD, which comes under the category of addiction and related disorders. Method The sample included 59 patients diagnosed with SA, who were compared to 2190 individuals diagnosed with GD and to 93 healthy controls. Assessment measures included the Diagnostic Questionnaire for Pathological Gambling, the South Oaks Gambling Screen, the Symptom CheckList-90 Items-Revised and the Temperament and Character Inventory-Revised. Results No statistically significant differences were found between the two clinical groups, except for socio-economic status. Although statistically significant differences were found between both clinical groups and controls for all scales on the SCL-90, no differences were found between the two clinical groups. The results were different for personality characteristics: logistic regression models showed that sex addictive behavior was predicted by a higher education level and by lower scores for TCI-R novelty-seeking, harm avoidance, persistence and self-transcendence. Being employed and lower scores in cooperativeness also tended to predict the presence of sex addiction. Conclusions While SA and GD share some psychopathological and personality traits that are not present in healthy controls, there are also some diagnostic-specific characteristics that differentiate between the two clinical groups. These findings may help to increase our knowledge of phenotypes existing in behavioral addictions.

Nannochloropsis is a genus of fast-growing microalgae that are regularly used for biotechnology applications. Nannochloropsis species have a high triacylglycerol content and their polar lipids are rich in the omega-3 long-chain polyunsaturated fatty acid, eicosapentaenoic acid. Placed in the heterokont lineage, the Nannochloropsis genus has a complex evolutionary history. Genome sequences are available for several species, and a number of transcriptomic datasets have been produced, making this genus a facile model for comparative genomics. There is a growing interest in Nannochloropsis species as models for the study of microalga lipid metabolism and as a chassis for synthetic biology. Recently, techniques for gene stacking, and targeted gene disruption and repression in the Nannochloropsis genus have been developed. These tools enable gene-specific, mechanistic studies and have already allowed the engineering of improved Nannochloropsis strains with superior growth, or greater bioproduction.

Significance Worldwide, potato is the third most important crop grown for direct human consumption, but breeders have struggled to produce new varieties that outperform those released over a century ago, as evidenced by the most widely grown North American cultivar (Russet Burbank) released in 1876. Despite its importance, potato genetic diversity at the whole-genome level remains largely unexplored. Analysis of cultivated potato and its wild relatives using modern genomics approaches can provide insight into the genomic diversity of extant germplasm, reveal historic introgressions and hybridization events, and identify genes targeted during domestication that control variance for agricultural traits, all critical information to address food security in 21st century agriculture., Cultivated potatoes (Solanum tuberosum L.), domesticated from wild Solanum species native to the Andes of southern Peru, possess a diverse gene pool representing more than 100 tuber-bearing relatives (Solanum section Petota). A diversity panel of wild species, landraces, and cultivars was sequenced to assess genetic variation within tuber-bearing Solanum and the impact of domestication on genome diversity and identify key loci selected for cultivation in North and South America. Sequence diversity of diploid and tetraploid S. tuberosum exceeded any crop resequencing study to date, in part due to expanded wild introgressions following polyploidy that captured alleles outside of their geographic origin. We identified 2,622 genes as under selection, with only 14–16% shared by North American and Andean cultivars, showing that a limited gene set drove early improvement of cultivated potato, while adaptation of upland (S. tuberosum group Andigena) and lowland (S. tuberosum groups Chilotanum and Tuberosum) populations targeted distinct loci. Signatures of selection were uncovered in genes controlling carbohydrate metabolism, glycoalkaloid biosynthesis, the shikimate pathway, the cell cycle, and circadian rhythm. Reduced sexual fertility that accompanied the shift to asexual reproduction in cultivars was reflected by signatures of selection in genes regulating pollen development/gametogenesis. Exploration of haplotype diversity at potato’s maturity locus (StCDF1) revealed introgression of truncated alleles from wild species, particularly S. microdontum in long-day–adapted cultivars. This study uncovers a historic role of wild Solanum species in the diversification of long-day–adapted tetraploid potatoes, showing that extant natural populations represent an essential source of untapped adaptive potential.

Nannochloropsis oceanica CCMP1779 is an oleaginous heterokont microalga that is particularly amenable to synthetic biology approaches. The underlying complex genetic engineering often requires the expression of multiple transgenes (gene stacking). We integrated several techniques into a vector toolkit for multi-gene expression, including: multiple resistance marker genes, bidirectional promoters, and assembly of multiple expression cassettes into a single vector. We developed a series of gateway entry and destination vectors for assembly of two bidirectional promoter expression cassettes, which facilitates combinatorial high-capacity gene stacking. Several endogenous bidirectional promoters were demonstrated to be effective for driving transgene expression, with a dual-luciferase reporter system used to monitor transgene expression under different environmental conditions. The bidirectional promoter between the nitrate reductase and the nitrate transporter genes drives nitrogen source dependent transcription, enabling conditional transgene expression. Lethal concentrations of the antibiotics, Blasticidin, G418, and Nourseothricin, were determined and the corresponding marker genes used for genomic transformation selection.

Circadian clocks synchronize various physiological, metabolic and developmental processes of organisms with specific phases of recurring changes in their environment (e.g. day and night or seasons). Here, we investigated whether the circadian clock plays a role in regulation of growth and chlorophyll (Chl) accumulation in Nannochloropsis gaditana, an oleaginous marine microalga which is considered as a potential feedstock for biofuels and for which a draft genome sequence has been published. Optical density (OD) of N. gaditana culture was monitored at 680 and 735 nm under 12:12 h or 18:6 h light-dark (LD) cycles and after switching to continuous illumination in photobioreactors. In parallel, Chl fluorescence was measured to assess the quantum yield of photosystem II. Furthermore, to test if red- or blue-light photoreceptors are involved in clock entrainment in N. gaditana, some of the experiments were conducted by using only red or blue light. Growth and Chl accumulation were confined to light periods in the LD cycles, increasing more strongly in the first half than in the second half of the light periods. After switching to continuous light, rhythmic oscillations continued (especially for OD680 ) at least in the first 24 h, with a 50% decrease in the capacity to grow and accumulate Chl during the first subjective night. Pronounced free-running oscillations were induced by blue light, but not by red light. In contrast, the photosystem II quantum yield was determined by light conditions. The results indicate interactions between circadian and light regulation of growth and Chl accumulation in N. gaditana.

Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.

Background Photosynthetic microalgae are considered a viable and sustainable resource for biofuel feedstocks, because they can produce higher biomass per land area than plants and can be grown on non-arable land. Among many microalgae considered for biofuel production, Nannochloropsis oceanica (CCMP1779) is particularly promising, because following nutrient deprivation it produces very high amounts of triacylglycerols (TAG). The committed step in TAG synthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT). Remarkably, a total of 13 putative DGAT-encoding genes have been previously identified in CCMP1779 but most have not yet been studied in detail. Results Based on their expression profile, six out of 12 type-2 DGAT-encoding genes (NoDGTT1-NoDGTT6) were chosen for their possible role in TAG biosynthesis and the respective cDNAs were expressed in a TAG synthesis-deficient mutant of yeast. Yeast expressing NoDGTT5 accumulated TAG to the highest level. Over-expression of NoDGTT5 in CCMP1779 grown in N-replete medium resulted in levels of TAG normally observed only after N deprivation. Reduced growth rates accompanied NoDGTT5 over-expression in CCMP1779. Constitutive expression of NoDGTT5 in Arabidopsis thaliana was accompanied by increased TAG content in seeds and leaves. A broad substrate specificity for NoDGTT5 was revealed, with preference for unsaturated acyl groups. Furthermore, NoDGTT5 was able to successfully rescue the Arabidopsis tag1-1 mutant by restoring the TAG content in seeds. Conclusions Taken together, our results identified NoDGTT5 as the most promising gene for the engineering of TAG synthesis in multiple hosts among the 13 DGAT-encoding genes of N. oceanica CCMP1779. Consequently, this study demonstrates the potential of NoDGTT5 as a tool for enhancing the energy density in biomass by increasing TAG content in transgenic crops used for biofuel production. Electronic supplementary material The online version of this article (doi:10.1186/s13068-016-0686-8) contains supplementary material, which is available to authorized users.