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Cellular asymmetry begins with the selection of a discrete point on the cell surface that triggers Rho-GTPases activation and localized assembly of the cytoskeleton to establish new growth zones. The cylindrical shape of fission yeast is organized by microtubules (MT) that deliver the landmark Tea1-Tea4 complex at the cell tips to define the growth poles. However, only a few tea1Δ cells mistaken the direction of growth, indicating that they manage to detect their growth sites. Here, we show that Rgf1 (Rho1-GEF) and Tea4 are components of the same complex and that Rgf1 activity toward Rho1 is required for strengthen Tea4 at the cell tips. Moreover, in cells lacking Tea1, selection of the correct growth site depends on Rgf1 and on a correctly polarized actin cytoskeleton, both necessary for Rho1 activation at the pole. We propose an actin-dependent mechanism driven by Rgf1-Rho1 that marks the poles independently of MTs and the Tea1-Tea4 complex.

BackgroundIn recent decades, the relationship between emotional disorders (i.e., depression and anxiety) and alterations in physiological functions (i.e., inflammation or metabolism) have been well supported. However, studies on a symptom-based approach have provided mixed results. Our study aims to gain insight into how subclinical statuses, featured by elevated depressive and/or anxious symptoms, may influence immunometabolic alterations in the concurrent relationship; and the development of metabolic diseases at 10-year follow-up: diabetes, hypertension and hypercholesterolemia.MethodsData from 758 Greek adults [394 men (aged 41 ± 10 years) and 364 women (aged 37 ± 12 years)] were used. Four groups were created according to the levels of depressive and anxiety symptoms: (1) control group (CG), (2) depressive group (DG), (3) anxiety group (AG) and (4) depressive and anxiety group (DAG). Multi-indicator multi-causes (MIMIC) modeling was used to estimate metabolic function and inflammatory response scores, on a wide selection of blood biomarkers. Finally, a binary logistic regression was carried out to study the influence of symptoms on the development of the aforementioned metabolic diseases on a 10-year follow-up.ResultsGroup membership was not associated with metabolic function score. Conversely, DAG membership was related with higher inflammatory response score (B = 0.20, CI95 = 0.01, 0.40), with respect to the CG (p < 0.05). Both age and sex were significant variables in the calculation of both scores. Regarding disease at 10-year follow-up effect, risk of developing diabetes, hypertension and hypercholesterolemia was associated with age and socioeconomic status. Moreover, DG membership was significant for diabetes risk (OR = 2.08, CI95 = 1.00, 4.22) and DAG for hypercholesterolemia (OR = 1.68, CI95 = 1.16, 2.43).LimitationsData on anti-inflammatory drugs and psychopharmacological medication were not collected in this study.ConclusionsElevated symptoms of depression and anxiety accounts for inflammatory alterations at concurrent relationship and a higher risk of 10-year follow-up metabolic diseases.

Introducción: El virus SARS-CoV-2 puede afectar múltiples órganos y sistemas, siendo el Sistema Nervioso Central (SNC) susceptible a complicaciones de forma aguda o por procesos inmunológicos secundarios desencadenados por este. Se han documentado expresiones como Síndrome Guillain Barré, encefalitis agudas o autoinmunes. Presentación de caso: Paciente femenino de 4 años quien presentó signos y síntomas de disfunción neurológica (crisis epiléptica, disautonomía, cambios conductuales) un mes posterior a infección por SARS-CoV-2. El resultado de líquido cefalorraquídeo (LCR) mostró celularidad levemente aumentada y anticuerpos neutralizantes o antiespículas presentes (positivo). Los hallazgos de la resonancia magnética cerebal (RMC) y electroencefalograma (EEG) fueron normales. Recibió tratamiento inmunomodulador con reversión total de los síntomas. Discusión: Las manifestaciones que ccomprometan al SNC pot-COVID, sin otras causas explicables, deben correlacionarse con encefalitis aguda o autoinmune dependientes del tiempo de presentación de los síntomas. Es imperativo la decisión terapéutica temprana para evitar complicaciones que comprometan el futuro del niño.

The Fossil Forest of the Aragoncillo Range is one of several paleontological sites of exceptional scientific value in the Sierra de Selas (Province of Guadalajara, central Spain). This shows an accumulation of silicified tree trunks along with well-preserved macro- and microflora of lower Permian age. This ancient forest, dominated by tree ferns and conifers, was destroyed by volcanic eruptions that took place in many continental areas at this time. This site is in the Molina-Alto Tajo UNESCO Global Geopark, but it is highly vulnerable and has suffered continued impact from plundering. The lack of implementation of legislation that guarantees its conservation does not allow interested visitors to enjoy the site and understand the characteristics of life and climate of such a unique ecosystem from this time in Earth history.

Understanding the phase behaviour of (CO2 + water + permanent gas) systems is critical for implementing carbon capture and storage (CCS) processes, a key technology in reducing CO2 emissions. In this paper, phase behaviour data for (H2O + N2) and (CO2 + H2O + N2) systems are reported at temperatures from 323 to 473 K and pressures up to 20 MPa. In the ternary system, the mole ratio between CO2 and N2 was 1. Experiments were conducted in a newly designed analytical apparatus that includes two syringe pumps for fluid injection, a high-pressure equilibrium vessel, heater aluminium jacket, Rolsi sampling valves and an online gas chromatograph (GC) for composition determination. A high-sensitivity pulsed discharge detector installed in the GC was used to measure the low levels of dissolved nitrogen in the aqueous phase and low water levels in the vapour phase. The experimental data were compared with the calculation based on the γ-φ and SAFT-γ Mie approaches. In the SAFT-γ Mie model, the like parameters for N2 had to be determined. We also obtained the unlike dispersion energy for the (H2O + N2) system and the unlike repulsive exponent and dispersion energy for the (CO2 + N2) system. This was done to improve the prediction of SAFT-γ Mie model. For the (H2O + N2) binary system, the results show that the solubility of nitrogen in the aqueous phase was calculated better by the γ-φ approach rather than the SAFT-γ Mie model, whereas SAFT-γ Mie performed better for the prediction of the vapour phase. For the (CO2 + H2O + N2) ternary systems, both models predicted the experimental data for each phase with good agreement.

Summary: Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)—many of which are refractory to current standard-of-care treatments—from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer. : Rokita et. al provide an extensively annotated genomic dataset of somatic oncogenic regulation across 37 distinct pediatric malignancies. The 261 patient-derived xenograft models are available to the scientific community, and the genomic annotations will enable rational preclinical agent prioritization and acceleration of therapeutic targets for early-phase pediatric oncology clinical trials. Keywords: pediatric cancer, patient-derived xenograft, relapse, whole-exome sequencing, transcriptome sequencing, copy number profiling, preclinical testing, classifier

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by cytochrome P450 epoxygenation of arachidonic acid, which are metabolized by EPHX2 (epoxide hydrolase 2, alias soluble epoxide hydrolase or sEH). EETs have pleiotropic effects, including anti-inflammatory activity. Using a Connectivity Map (CMAP) approach, we identified an inverse-correlation between an exemplar EPHX2 inhibitor (EPHX2i) compound response and an inflammatory bowel disease patient-derived signature. To validate the gene-disease link, we tested a pre-clinical tool EPHX2i (GSK1910364) in a mouse disease model, where it showed improved outcomes comparable to or better than the positive control Cyclosporin A. Up-regulation of cytoprotective genes and down-regulation of proinflammatory cytokine production were observed in colon samples obtained from EPHX2i-treated mice. Follow-up immunohistochemistry analysis verified the presence of EPHX2 protein in infiltrated immune cells from Crohn's patient tissue biopsies. We further demonstrated that GSK2256294, a clinical EPHX2i, reduced the production of IL2, IL12p70, IL10 and TNFα in both ulcerative colitis and Crohn's disease patient-derived explant cultures. Interestingly, GSK2256294 reduced IL4 and IFNγ in ulcerative colitis, and IL1β in Crohn's disease specifically, suggesting potential differential effects of GSK2256294 in these two diseases. Taken together, these findings suggest a novel therapeutic use of EPHX2 inhibition for IBD.

Summary: Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these “hidden responders” may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. : Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines. Keywords: Gene expression, machine learning, Ras, NF1, KRAS, NRAS, HRAS, pan-cancer, TCGA, drug sensitivity

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

[This corrects the article DOI: 10.1371/journal.pone.0184164.].

Endoplasmic reticulum stress plays a critical role to restore the homeostasis of protein production in eukaryotic cells. This vital process is hence involved in many types of diseases including COPD. PERK, one branch in the ER stress signaling pathways, has been reported to activate NRF2 signaling pathway, a known protective response to COPD. Based on this scientific rationale, we aimed to identify PERK activators as a mechanism to achieve NRF2 activation. In this report, we describe a phenotypic screening assay to identify PERK activators. This assay measures phosphorylation of GFP-tagged eIF2α upon PERK activation via a cell-based LanthaScreen technology. To obtain a robust assay with sufficient signal to background and low variation, multiple parameters were optimized including GFP-tagged eIF2α BacMam concentration, cell density and serum concentration. The assay was validated by a tool compound, Thapsigargin, which induces phosphorylation of eIF2α. In our assay, this compound showed maximal signal window of approximately 2.5-fold with a pEC50 of 8.0, consistent with literature reports. To identify novel PERK activators through phosphorylation of eIF2α, a focused set of 8,400 compounds was screened in this assay at 10 µM. A number of hits were identified and validated. The molecular mechanisms for several selected hits were further characterized in terms of PERK activation and effects on PERK downstream components. Specificity of these compounds in activating PERK was demonstrated with a PERK specific inhibitor and in PERK knockout mouse embryonic fibroblast (MEF) cells. In addition, these hits showed NRF2-dependent anti-oxidant gene induction. In summary, our phenotypic screening assay is demonstrated to be able to identify PERK specific activators. The identified PERK activators could potentially be used as chemical probes to further investigate this pathway as well as the link between PERK activation and NRF2 pathway activation.

The Zscan4 family of genes, encoding SCAN-domain and zinc finger-containing proteins, has been implicated in the control of early mammalian embryogenesis as well as the regulation of pluripotency and maintenance of genome integrity in mouse embryonic stem cells. However, many features of this enigmatic family of genes are poorly understood. Here we show that undifferentiated mouse embryonic stem cell (ESC) lines simultaneously express multiple members of the Zscan4 gene family, with Zscan4c, Zscan4f and Zscan4-ps2 consistently being the most abundant. Despite this, between only 0.1 and 0.7% of undifferentiated mouse pluripotent stem cells express Zscan4 protein at a given time, consistent with a very restricted pattern of Zscan4 transcripts reported previously. Herein we demonstrate that Zscan4 expression is regulated by the p110α catalytic isoform of phosphoinositide 3-kinases and is induced following exposure to a sub-class of DNA-damage-inducing agents, including Zeocin and Cisplatin. Furthermore, we observe that Zscan4 protein expression peaks during the G2 phase of the cell cycle, suggesting that it may play a critical role at this checkpoint. Studies with GAL4-fusion proteins suggest a role for Zscan4 in transcriptional regulation, further supported by the fact that protein interaction analyses demonstrate that Zscan4 interacts with both LSD1 and CtBP2 in ESC nuclei. This study advances and extends our understanding of Zscan4 expression, regulation and mechanism of action. Based on our data we propose that Zscan4 may regulate gene transcription in mouse ES cells through interaction with LSD1 and CtBP2.

Pancreatic ductal adenocarcinomas contain a subset of exclusively tumorigenic cancer stem cells (CSCs), which are capable of repopulating the entire heterogeneous cancer cell populations and are highly resistant to standard chemotherapy. Here we demonstrate that metformin selectively ablated pancreatic CSCs as evidenced by diminished expression of pluripotency-associated genes and CSC-associated surface markers. Subsequently, the ability of metformin-treated CSCs to clonally expand in vitro was irreversibly abrogated by inducing apoptosis. In contrast, non-CSCs preferentially responded by cell cycle arrest, but were not eliminated by metformin treatment. Mechanistically, metformin increased reactive oxygen species production in CSC and reduced their mitochondrial transmembrane potential. The subsequent induction of lethal energy crisis in CSCs was independent of AMPK/mTOR. Finally, in primary cancer tissue xenograft models metformin effectively reduced tumor burden and prevented disease progression; if combined with a stroma-targeting smoothened inhibitor for enhanced tissue penetration, while gemcitabine actually appeared dispensable.

Maintenance of embryonic stem cell (ESC) self-renewal and pluripotency are controlled by extrinsic factors, molecular signaling pathways and transcriptional regulators. While many of the key players have been studied in depth, how the molecular signals interact with transcription factors of the pluripotency network to regulate their action remains less well understood. Inhibition of glycogen synthase kinase 3 (Gsk-3) has been implicated in the maintenance of mouse ESC pluripotency, although there is contradictory data on its role, with enhancement of cell survival and metabolism, stabilisation of c-Myc and activation of Wnt signalling proposed as potential mechanisms. We have discovered that suppression of Gsk-3 activity leads to enhanced protein levels of key transcriptional regulators of the pluripotency network, notably Nanog, Tbx3 and c-Myc. Protein stability was unchanged following Gsk-3 inhibition, although interestingly, Nanog and Tbx3 proteins were found to have half-lives of 1-3 h, while that of Oct4 protein was longer, at 6 h. We demonstrate that the effects on protein levels seen following inhibition of Gsk-3 are due to both enhanced de novo synthesis of Nanog protein and increases in the proportion of Nanog and Tbx3 RNAs bound to polysomes, findings consistent with Gsk-3 regulating translation of these factors. These effects were not due to changes in regulators of general translation initiation machinery nor mediated via the 5' or 3' UTR sequences of Nanog alone. The data we present provide both new conceptual insight into the mechanisms regulated by Gsk-3 that may contribute to ESC self-renewal and, importantly, establish control of protein translation as an additional mechanism involved in modulation of ESC pluripotency.

The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs), exhibiting properties similar to those of embryonic stem cells (ESCs), has attracted much attention, with many studies focused on improving efficiency of derivation and unraveling the mechanisms of reprogramming. Despite this widespread interest, our knowledge of the molecular signaling pathways that are active in iPSCs and that play a role in controlling their fate have not been studied in detail. To address this shortfall, we have characterized the influence of different signals on the behavior of a model mouse iPSC line. We demonstrate significant responses of this iPSC line to the presence of serum, which leads to profoundly enhanced proliferation and, depending on the medium used, a reduction in the capacity of the iPSCs to self-renew. Surprisingly, this iPSC line was less sensitive to withdrawal of LIF compared to ESCs, exemplified by maintenance of expression of a Nanog-GFP reporter and enhanced self-renewal in the absence of LIF. While inhibition of phosphoinositide-3 kinase (PI3K) signaling decreased iPSC self-renewal, inhibition of Gsk-3 promoted it, even in the absence of LIF. High passages of this iPSC line displayed altered characteristics, including genetic instability and a reduced ability to self-renew. However, this second feature could be restored upon inhibition of Gsk-3. Collectively, our data suggest modulation of Gsk-3 activity plays a key role in the control of iPSC fate. We propose that more careful consideration should be given to characterization of the molecular pathways that control the fate of different iPSC lines, since perturbations from those observed in naïve pluripotent ESCs could render iPSCs and their derivatives susceptible to aberrant and potentially undesirable behaviors.

Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA.

En 2008, México figuraba como el segundo productor mundial (14.94%) de limones y el primero como exportador (20.5%), principalmente de limón persa, por lo que el objetivo de la investigación fue identificar y valorar aquellos factores que determinan la demanda de importaciones de limón persa en Estados Unidos, principal mercado destino (94.7%). Bajo el supuesto de que dicho mercado ofrece una capacidad real de expansión para los productores mexicanos de este cultivo, se formuló un modelo de regresión múltiple, considerando el ingreso, tipo de cambio (peso/dólar), precio unitario de importación y la demanda de importaciones,  estimado por el método de Mínimos Cuadrados Ordinarios (MCO); con datos anuales del  periodo 1994-2008, obteniendo también las elasticidades de la demanda. La variable de mayor  respuesta fue el ingreso con una elasticidad de 3.8, clasificando al limón persa como un bien normal superior; seguido del tipo de cambio  (0.83) y el precio (-0.666). Se concluyó, que es factible mantener el nivel de crecimiento actual de demanda de importaciones de limón persa, del 9.3% promedio anual, debido a que el incremento requerido en el ingreso real de Estados Unidos sería del 2.45% (ceteris paribus), contra el crecimiento observado del 2.9% en el periodo de estudio.

The aim of this study was to analyse the presence of emotional and behavioural difficulties in adolescents and their relationship with personal (age and sex) and contextual (level of psychosocial risk) variables. The sample consisted of 802 participants (48.6% girls, 51.4% boys) aged between 9 and 16 years (M = 11.97, SD = 1.40). The Strengths and Difficulties Questionnaire (SDQ) and the Psychosocial Risk Index were used. Significant differences were found as a function of sex, age and risk level. The presence of problems increased with age and under more adverse psychosocial conditions. The behavioural symptoms were more frequent in the boys, and the emotional symptoms and prosocial behaviours were more frequent in the girls. The regression analyses confirmed the predictive capacity of these variables. These results have implications for the understanding of mental health difficulties in adolescence, and they guide in the prevention for this population group.

Children born preterm (≤ 37 weeks) are at higher risk of developing cognitive problems and score lower on cognitive developmental assessments than full-term children. The objective of the paper is to analyse the impact of correction for prematurity on IQ scores amongst preterm born children at school age. A sample of 153 Spanish school-age children were assessed using the WISC-V (Full Scale IQ and all indexes). Assessments were re-scored based on corrected age. Pairwise t-tests were used to analyse the difference in mean IQ scores between corrected age and uncorrected (chronological) age. WISC-V IQ scores

The aims of the present study were to observe the values of balance, Motor Competence (MC) and Perceived Motor Competence (PMC) in pupils between 7 and 8 years of age, as well as to find out the effect of a program focused on balance work over MC, PMC and balance itself, and the differences according to sex. The sample consisted of 10 boys and 7 girls, belonging to the second year of Primary Education (Mage = 7.6 years; SD = .24). A pre-experimental repeated measures study design was used. The instruments used were the Test of Gross Motor Development (TGMD-3) to analyse actual motor competence, the Pictographic Scale of Perceived Motor Skills Competence (PMSC) to analyse their perceived motor competence, and the Stability Skills test for balance. A 10-session programme, in which balance was the main aim, was implemented. The results indicated improvements in all dimensions, with differences according to the gender of the participants. Therefore, it can be concluded that specific balance work can improve not only balance but also real and perceived motor competence, although more studies are needed on sex differences.

Research on health-related quality of life (HRQoL) of school-aged children born preterm (< 37 weeks of gestational age) is scarce and there are few studies examining the relationship with medical and family factors. The aims were to analyze HRQoL in a sample of 8-year-old children born preterm with very low birth weight (VLBW), to test a proposed theoretical model that examines the relationship with medical and socio-family factors, and to explore the mediation effects of maternal factors between perinatal variables, demographic characteristics and HRQoL. A total of 147 VLBW children and 116 mothers were assessed. The measures included for assessment were self-and parent-reported HRQoL, functional social support, maternal stress, socio-family risk index and neonatal medical risk index. Mediation analysis was applied to investigate mediation effects of the maternal factors. Mean self-and parent-reported KIDSCREEN scores were 55.1 (SD 10.1) and 58.2 (SD 9.1), respectively, indicating better HRQoL than the normed sample with a mean of 50 (p

BackgroundPersonality disorders may influence sexual behaviours and sexual dysfunction.AimOur main objective was to analyse the influence of personality disorders (PDs) in patients with erectile dysfunction (ED) of psychological origin that fail to respond to andrological treatment with Phosphodiesterase-5 inhibitors (IPDE5), assessing whether there are differences in sexual behaviours and response to psychosexual treatment.MethodsThe research is designed as an ex post facto retrospective study with two groups. A control group of 23 men with ED without personality disorders and a group of 51 men with both ED and PDs.ResultsIn the case sample, 34.30% of the participants presented more than one personality disorder. No significant differences were found in sexual behaviours except for heteromasturbation (men without PDs masturbated their partners more to satisfy them than men with PDs), and men with PDs considered themselves less premature ejaculators than the control group. Finally, 82.14% of the control group did well with psychosexual therapy compared to 53.85% of the PDs group.ConclusionPsychosexual treatment of ED has a worse outcome if the men also have PDs. Strengths and Limitations: from a clinical standpoint, it is important to assess the presence of personality disorders in men with ED and to implement psychosexual strategies to improve the response to treatment in these cases. Confirmation of the results with a much larger sample becomes necessary.