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Danielle Soares Bio,1 Márcio Gerhardt Soeiro-de-Souza,1 Maria Concepción Garcia Otaduy,2 Rodrigo Machado-Vieira,3 Ricardo Alberto Moreno11Mood Disorders Unit, 2Institute of Radiology, Department and Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil; 3Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIMH NIH, Bethesda, MD, USAIntroduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls.Material and methods: Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus.Results: The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness.Conclusion: Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning.Keywords: bipolar disorder, social cognition, facial emotion recognition

Resumen: En el siguiente trabajo tiene como tema la formación de identidades a partir del análisis una serie de variables y la explicación de las mismas mediante el planteamiento de un modelo estructural. De manera más concreta nos hemos centrado en la formación de la identidad nacional, entendida como la identificación con el estado nación, y la relación de este sentimiento con respecto a otras formas de identidad que tienen como base otros ámbitos territoriales y políticos superiores o inferiores, así como con el uso de una u otra lengua en el hogar u otras formas de identidad ligadas a ámbitos culturales o comunitarios diferentes como puede ser la familia, siendo estas últimas formas de identidad propias de unos valores postmodernos.Abstract: In the following work has as it feared the training of identities from the analysis of variables and the explanation of the same by means of a structural model. Of way more concrete have centered us in the training of the national identity, understood like the identification with the been nation, and the relation of this feeling regarding other forms of identity that have as it base other territorial fields and upper politician, or inferior; like this as with the use of one or another tongue in the home or other forms of identity tied to cultural fields or communities different as it can be the family, being these last forms of proper identity of some values post modern.

Objective. To evaluate cytology laboratories and the performance of cytotechnologists for establishing efficient external quality control for Mexico's National Program for the Prevention and Control of Cervical Cancer. Material and Methods. During January and February 1998, an on-site evaluation of all cytology laboratories of the Ministry of Health found that only 70% of the microscopes were in adequate working conditions, reagents were out of date, and working conditions were sub-optimal. A program for external quality control based on proficiency testing was established for cytotechnologists. Fifty slide sets with 20 Papanicolaou slides and 10 photographic slides were prepared. The sets were given to the cytotechnologists for evaluation and again one year later by courier. Results. Twenty-one percent of microscopes were repaired and 9% replaced; reagents were distributed and laboratory facilities improved. Only 16% of cytotechnologists passed the initial proficiency test. Cytotechnologists received a refresher training course: one year later 67% of them passed the proficiency test. To ascertain that each slide was correctly diagnosed, 41 sets were rescreened by expert cytopathologists or cytologists and their diagnoses compared to the original ones. Thirty-seven sets had 86% to 96% concordance. Conclusions. This new system for external quality control of cervical cytology allowed the opportune and reliable evaluation of the performance of cytotechnologists.

O presente trabalho faz uma análise do conceito de variabilidade comportamental com o objetivo de padronizar as diferentes definições e usos do termo. Propomos: 1) uma definição que recorra ao ponto comum dentre os diversos conceitos de variabilidade existentes na literatura, e 2) a descrição e sistematização dos aspectos específicos de cada uso do termo, utilizando os seguintes critérios: conteúdo e estrutura de cada conceito, níveis de análise empírico/teórico, molar/molecular, e tipos de medida e códigos com que são especificados. Essa análise é uma tentativa inicial para a construção de uma taxonomia da variabilidade comportamental.

In order to increase the storage capacity of the East Spent Fuel Pool at the Cofrentes NPP, located in Valencia province, Spain, the existing storage stainless steel racks were replaced by a new design of compact borated stainless steel racks allowing a 65% increase in fuel storing capacity. Calculation of the activation of the used racks was successfully performed with the use of MCNP4B code. Additionally the dose rate at contact with a row of racks in standing position and behind a wall of shielding material has been calculated using MCNP4B code as well. These results allowed a preliminary definition of the burnker required for the storage of racks. Recently the activity in the racks has been recalculated with SEACAB system which combines the mesh tally of MCNP codes with the activation code ACAB, applying the rigorous two-step method (R2S) developed at home, benchmarked with FNG irradiation experiments and usually applied in fusion calculations for ITER project.

Abstract Background The standardisation of the assessment methodology and case definition represents a major precondition for the comparison of study results and the conduction of meta-analyses. International guidelines provide recommendations for the standardisation of falls methodology; however, injurious falls have not been targeted. The aim of the present article was to review systematically the range of case definitions and methods used to measure and report on injurious falls in randomised controlled trials (RCTs) on fall prevention. Methods An electronic literature search of selected comprehensive databases was performed to identify injurious falls definitions in published trials. Inclusion criteria were: RCTs on falls prevention published in English, study population ≥ 65 years, definition of injurious falls as a study endpoint by using the terms "injuries" and "falls". Results The search yielded 2089 articles, 2048 were excluded according to defined inclusion criteria. Forty-one articles were included. The systematic analysis of the methodology applied in RCTs disclosed substantial variations in the definition and methods used to measure and document injurious falls. The limited standardisation hampered comparability of study results. Our results also highlight that studies which used a similar, standardised definition of injurious falls showed comparable outcomes. Conclusions No standard for defining, measuring, and documenting injurious falls could be identified among published RCTs. A standardised injurious falls definition enhances the comparability of study results as demonstrated by a subgroup of RCTs used a similar definition. Recommendations for standardising the methodology are given in the present review.

Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive cognitive decline. Cholinesterase inhibitors are commonly used to manage symptoms but have limited efficacy as the disease progresses. Aducanumab, a monoclonal antibody targeting amyloid-β (Aβ) plaques, has emerged as a novel therapeutic approach. Despite its Food and Drug Administration (FDA) approval, its efficacy and safety remain contentious, particularly following the European Medicines Agency's (EMA's) rejection. This systematic review aims to evaluate the efficacy, safety, and clinical outcomes of aducanumab in treating mild AD. Adhering to Preferred Reporting Items for Systematic Reviews (PRISMA) 2020 guidelines, we conducted a comprehensive search of PubMed and Science Direct databases, including randomized controlled trials (RCTs), cohort studies, and case-control studies focusing on aducanumab versus placebo in mild AD. Studies were screened based on predefined inclusion and exclusion criteria, and data were extracted on clinical outcomes, biomarkers, and neuroimaging markers. The risk of bias was assessed using the Cochrane Handbook and Newcastle-Ottawa Scale. Out of 967 identified records, seven studies met the inclusion criteria. Findings indicated a dose-dependent reduction in Aβ plaques with aducanumab, but clinical outcomes varied. High-dose aducanumab (10 mg/kg) demonstrated significant improvements in some studies but not others. Adverse events, notably amyloid-related imaging abnormalities (ARIA), were frequent, especially at higher doses. The studies exhibited heterogeneous treatment effects and underscored the potential of cerebrospinal fluid biomarkers as an alternative to amyloid positron emission tomography (PET) scans. Aducanumab shows promise in reducing Aβ plaques and has potential clinical benefits at high doses; however, its safety profile, particularly concerning ARIA, remains a significant concern. The variability in clinical efficacy highlights the need for further research to optimize dosing regimens and identify patient populations most likely to benefit from treatment. Future studies should focus on refining treatment protocols and exploring alternative biomarkers to improve therapeutic outcomes for AD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Medel Sánchez et al.)

Purpose: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity., Methods and Materials: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint., Results: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003)., Conclusions: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Central illustration : Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases., Background: The search for clinically useful methods to assess atherosclerotic diseases (ASCVD) with good accuracy, low cost, non-invasiveness, and easy handling has been stimulated for years. Thus, the atherogenic indices evaluated in this study may fit this growing demand., Objectives: To assess the potential of atherogenic indices to evaluate patients with clinical atherosclerosis., Methods: Single-center cross-sectional study, through which the Castelli I and II indices, the atherogenic index of plasma (AIP), the lipoprotein combine index, and the variation in the peripheral perfusion index between 90 and 120 seconds after an endothelium-dependent (ΔPI90-120) vasodilator stimulus were evaluated in the prediction of atherosclerosis. Statistical significance was set at p < 0.05., Results: The sample consisted of 298 individuals with an average age of 63.0±16.1 years, of which 57.4% were women. Paired comparisons of the ROC curve analysis of the indices that reached the area under the curve (AUC) > 0.6 show that ΔPI90-120 and AIP were superior to other indices, and no differences were observed between them (difference between AUC = 0.056; 95%CI -0.003-0.115). Furthermore, both the ΔPI90-120 [odds ratio (OR) 9.58; 95%CI 4.71-19.46)] and AIP (OR 5.35; 95%CI 2.30-12.45) were independent predictors of clinical atherosclerosis., Conclusions: The AIP and ΔPI90-120 represented better accuracy in discriminating clinical ASCVD. Moreover, they were independent predictors of clinical ASCVD, evidencing a promising possibility for developing preventive and control strategies for cardiovascular diseases. Therefore, they are markers for multicenter studies from the point of view of practicality, low cost, and external validity.

In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Purpose: Central nervous system (CNS) metastases are a significant burden in breast cancer (BC). Capecitabine is a frequent choice in this scenario, but data supporting its single-agent activity are scarce. We aimed to evaluate the intracranial efficacy of capecitabine in CNS metastases from BC., Methods: This retrospective cohort included patients with CNS metastases from BC treated with capecitabine at a single centre. Study endpoints were intracranial CNS objective response rate (CNS-ORR), intracranial CNS disease control rate (CNS-DCR), intracranial CNS progression-free survival (CNS-PFS) and overall survival (OS)., Results: 209 patients were included; 41.6% hormone receptor-positive HER2-negative (HR + HER2-), 33.9% human epidermal growth factor receptor 2 positive (HER2+), and 26.4% triple-negative breast cancer (TNBC). Radiotherapy was performed in 90.4% and CNS surgery in 27.5%. Among patients accessible for intracranial response, 3-month CNS-ORR and CNS-DCR were 41.6% and 81.2%. CNS-ORR was numerically higher among TNBC (61% versus 38% in HR + HER2-BC and 35% in HER2 + BC) ( p = 0.194). When considering patients who were not evaluable at 3-month as non-responders, the 3-month CNS-ORR was 19.1% (18.4% in HR + HER2-, 18.3% in HER2+, and 21.6% in TNBC). Nevertheless, TNBC was associated with lower CNS-PFS ( p < 0.001) and OS ( p < 0.001). Median PFS was 8.3 months in HR + HER2-, 5.0 months in HER2+, and 3.0 months in TNBC. Median OS was 8.7, 9.1 and 4.5 months, respectively., Conclusion: Among patients with BC and CNS metastases accessible for intracranial response at 3 months, intracranial activity was observed with capecitabine. These patients have a poor prognosis regardless of the BC subtype, especially in scenarios where newer therapeutic options are unavailable., Competing Interests: MCG, CMHF, RAM, HCBRA, ASF: No conflicts of interest. LT: Consulting or Advisory Role: Lilly, Novartis, MSD, AstraZeneca, Daiichi-Sankyo; Educational Support: Pfizer, Lilly, Zodiac, AstraZeneca; Speaker: Novartis, Roche, Pfizer, Zodiac, Lilly, MSD, AstraZeneca, Daichii-Sankyo; Institutional Research Funding: Novartis. RCB: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Nestle; Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo; Institutional Research Funding: Novartis, AstraZeneca., (© the authors; licensee ecancermedicalscience.)

Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America., Methods: Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management., Results: The expert panel agreed that 'treatment-resistant depression' (TRD) is defined as 'failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode'. A stepwise treatment approach should be employed for the management of TRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Nonpharmacological treatments, such as electroconvulsive therapy, are also appropriate options for patients with TRD., Conclusion: These consensus recommendations on the operational definition of TRD and approved treatments for its management can be adapted to local contexts in the Latin American countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with TRD., (Copyright © 2023 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Strain represents the quantification of regional tissue deformation within a given area. Myocardial strain has demonstrated considerable utility as an indicator for the assessment of cardiac function. Notably, it exhibits greater sensitivity in detecting subtle myocardial abnormalities compared to conventional cardiac function indices, like left ventricle ejection fraction (LVEF). Nonetheless, the estimation of strain poses considerable challenges due to the necessity for precise tracking of myocardial motion throughout the complete cardiac cycle. This study introduces a novel deep learning-based pipeline, designed to automatically and accurately estimate myocardial strain from three-dimensional (3D) cine-MR images. Consequently, our investigation presents a comprehensive pipeline for the precise quantification of local and global myocardial strain. This pipeline incorporates a supervised Convolutional Neural Network (CNN) for accurate segmentation of the cardiac muscle and an unsupervised CNN for robust left ventricle motion tracking, enabling the estimation of strain in both artificial phantoms and real cine-MR images. Our investigation involved a comprehensive comparison of our findings with those obtained from two commonly utilized commercial software in this field. This analysis encompassed the examination of both intra- and inter-user variability. The proposed pipeline exhibited demonstrable reliability and reduced divergence levels when compared to alternative systems. Additionally, our approach is entirely independent of previous user data, effectively eliminating any potential user bias that could influence the strain analyses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Catharine De Vita Graves reports financial support was provided by Canon Medical Systems Corporation. Marina F. S. Rebelo reports financial support was provided by Canon Medical Systems Corporation. Ramon A. Moreno reports financial support was provided by Canon Medical Systems Corporation. Cesar H. Nomura reports financial support was provided by Canon Medical Systems Corporation. Marco A. Gutierrez reports financial support was provided by Canon Medical Systems Corporation. Catharine De Vita Graves has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Marina F. S. Rebelo has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Ramon A. Moreno has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial. Cesar H. Nomura has patent #BR512022001946-9 licensed to INPI - Instituto Nacional da Propriedade Industrial. Marco A. Gutierrez has patent #BR512022001946-9 licensed to INPI – Instituto Nacional da Propriedade Industrial., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The epidemiology of chronic hepatitis B (CHB) in Spain has changed due to migratory movements and the implementation of vaccination programs. The objective is to determine if prevalence has also changed amongst in Catalonia and the potential predictive variables of the infection., Material and Method: Observational cross-sectional multi-centre study of CHB prevalence. Epidemiological and clinical variables were included, and their predictive capacity is analysed by means of a multivariable logistic regression model., Results: A total of 6508 prisoners were studied. CHB prevalence was 1.7%, much less than in studies carried out in previous years. In inmates from North Africa, Asia, Eastern Europe, and Sub-Saharan Africa the CHB rate was 2.8, 4.2, 4.9 and 16.2 times higher, respectively, than amongst those born in Spain, which was 0.6%, the same as in the general population. CHB was associated with: a) being an immigrant [2.6%; OR: 4.18 (CI: 2.50-6.90; P <0.001); b) being unvaccinated (3.1%; OR: 0.13; CI: 0.06-0.26; P <0.001); and c) being infected by the human immunodeficiency virus (HIV) [3.9%; OR: 3.23; CI: 1.24-8.40; P = 0.016]., Conclusion: Vaccination against HBV (hepatitis B virus) has greatly reduced CHB prevalence in inmates over the past 30 years but remains high in immigrants and those with HIV. We recommend: a) maintaining HBV screening amongst inmates; b) continuing with vaccination programmes; and c) referring CHB cases to specialized programs for further study and treatment if needed.

Background: Distorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients' perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period., Method: These are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24., Results: Results showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment., Conclusion: Cognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions., Trial Registration: NCT02268487., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer's disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus-receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that central NgR1 surfaces form a bridge between two copies of viral capsid protein σ3, establishing that σ3 serves as a receptor ligand for reovirus. This unusual binding interface produces high-avidity interactions between virus and receptor to prime early entry steps. These studies refine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.

The high prevalence of psychiatric symptoms among juvenile delinquents is a well-replicated international finding. This study aimed to find the prevalence of mood disorders and their relationship with serious criminal acts in a population of adolescents in conflict with the law and in custody. A total of 123 male inmates aged 14 to 17 years were interviewed and assessed. Mood disorders were diagnosed in 15% of the sample for current episode and 31% for lifetime, making them third most prevalent after dependence disorders and disruptive disorders. The psychopathological profile of the adolescents who had committed violent crimes corroborates other studies reporting a high prevalence of mood disorders in this population. Several factors have been found to influence the formation of juvenile delinquency, including absence of family structure, social inequality, lack of quality school education, alcohol and drug abuse/addiction and disruptive disorders. The present results confirm mood disorders as another such factor., Competing Interests: Eduardo Alves Guilherme has declared no conflicts of interest. Ricardo Alberto Moreno has declared no conflicts of interest., (© 2023 The Australian and New Zealand Association of Psychiatry, Psychology and Law.)

Background: Although first-generation drug-eluting stent (DES) devices have effectively achieved their main goal of reducing restenosis, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization, and local drug toxicity, which ultimately prompted the development of new-generation DES options carrying biocompatible or even biodegradable polymers., Aims: We sought to assess the vessel-healing pattern of the novel sirolimus-eluting Inspiron DES (Scitech Medical) using serial optical coherence tomography (OCT) and assuming the hypothesis that this thin-strut (75-μm), biodegradable-polymer DES promotes a faster healing, with very early strut coverage., Methods: This is a prospective, multicenter, open-label, single-arm study enrolling 68 patients who underwent percutaneous coronary intervention guided by OCT. These patients were consecutively assigned into 3 groups. The first group had its OCT imaging follow-up performed at 3 months, the second group at 2 months, and the third group at 1 month., Results: Mean age was 59.5 years, 70.6% were male, 41.2% had type 2 diabetes, and 29.4% presented with acute coronary syndrome. A total of 72 lesions were treated and 1.06 stents were implanted per patient. OCT assessment of the stents at 1, 2, and 3 months showed a strut coverage of 90.41%, 93.96%, and 97.21%, respectively (P=.04)., Conclusion: The Inspiron DES showed an early strut healing pattern, with >90% of the struts covered by neointima within the first month and with almost all struts covered by the third month.

Objective: To enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease., Methods: This is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm² and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC., Results: Among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01)., Conclusions: At long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.

Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms, with a one-year survival rate below 20%. Axial methods (computed tomography and magnetic resonance imaging) play a fundamental role in the diagnosis and staging of the disease, because they provide adequate anatomical resolution in the assessment of key structures, mainly vascular structures. Pancreatic ductal adenocarcinoma is most often discovered in advanced stages, when surgical resection is no longer feasible. In that scenario, minimally invasive treatment alternatives have been developed in attempts to change the natural history of the disease. Irreversible electroporation, an interventional procedure that minimizes deleterious effects on adjacent tissues, has proven useful for the treatment of tumors traditionally considered unresectable. Despite the growing acknowledgment of this technique as a tool for the management of pancreatic ductal adenocarcinoma, it is still relatively unknown among radiologists. In this study, we sought to provide an overview of the main characteristics and eligibility criteria that must be considered for the indication of irreversible electroporation in cases of pancreatic ductal adenocarcinoma.

Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 μM) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 μM) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA 2 6.09) and L-NAME pre-treated endothelium-intact (pA 2 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 μM). In the thromboxane A 2 mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 μM) and the dopamine D 2 -receptor antagonist haloperidol (1 nM-1 μM) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D 2 -like receptor antagonist., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms., Methods: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions., Results: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample., Conclusion: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression., Competing Interests: DFT has worked as speaker and a scientist in the last 2 years for Cristália, Aché, Torrent, Abbott, and Lundbeck. DHM has worked as speaker and a scientist in the last 2 years for Aché, Torrent, Abbott, and Lundbeck. EV has received grants and served as consultant, advisor, or continuing medical education speaker for the following entities (unrelated to the present work): AB-Biotics, Abbvie, Aimentia, Angelini, Biogen, Celon, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Janssen, Lundbeck, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. ARB is chief medical advisor of Flowt and has a small equity in the company. The other authors report no conflicts of interest.

Objective: Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, can promote rapid action in the management of individuals with treatment-resistant depression (TRD) at sub-anesthetic doses. However, few studies have investigated the long-term use of ketamine administered intravenously (IV) and intranasally (IN). We report the design and rationale of a therapeutic trial for assessing the efficacy, safety, and tolerability of repeated-dose intramuscular (IM) ketamine vs. active treatment (escitalopram and aripiprazole) in TRD patients., Methods: A comparative, parallel-group, randomized double-blind trial assessing the efficacy, safety, and tolerability of acute (4 weeks) and maintenance (24 weeks) use of IM ketamine (0.75 mg/kg) vs. active control (escitalopram 15 mg and aripiprazole 5 mg) in individuals with moderate-severe intensity TRD (no psychotic symptoms) with or without suicide risk will be conducted. Patients with TRD (18-40 years) will be randomized and blinded to receive ketamine IM or active treatment at a 1:1 ratio for 4 weeks (active treatment) and 24 weeks (maintenance treatment). Subjects will be assessed using clinical scales, monitored for vital signs (VS) after application of injectable medication, and undergo neuropsychological tests. The primary outcome will be changed on the Montgomery-Åsberg Depression Rating Scale (MADRS) during the course of the trial. The study is in running., Results: This study can potentially yield evidence on the use of IM ketamine in the treatment of depressive disorders as an ultra-rapid low-cost therapy associated with less patient discomfort and reduced use of medical resources, and can elucidate long-term effects on different outcomes, such as neuropsychological aspects., Conclusions: The trial can help promote the introduction of a novel accessible approach for the treatment of complex disease (TRD) and also allow refinement of its long-term use., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04234776, identifier: NCT04234776., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cigognini, Guirado, Meene, Schneider, Salomon, Alexandria, Adriano, Thaler, Fernandes, Carneiro and Moreno.)

Accurate quantification of myocardium strain in magnetic resonance images is important to correctly diagnose and monitor cardiac diseases. Currently, available methods to estimate motion are based on tracking brightness pattern differences between images. In cine-MR images, the myocardium interior presents an inhered homogeneity, which reduces the accuracy in estimated motion, and consequently strain. Neural networks have recently been shown to be an important tool for a variety of applications, including motion estimation. In this work, we investigate the feasibility of quantifying myocardium strain in cardiac resonance synthetic images using motion generated by a compact and powerful network called Pyramid, Warping, and Cost Volume (PWC). Using the motion generated by the neural network, the radial myocardium strain obtained presents a mean average error of 12.30% +- 6.50%, and in the circumferential direction 1.20% +-0.61 %, better than the two classical methods evaluated. Clinical Relevance- This work demonstrates the feasibility of estimating myocardium strain using motion estimated by a convolutional neural network.

Background: The importance of blockchain-based architectures for personal health record (PHR) lies in the fact that they are thought and developed to allow patients to control and at least partly collect their health data. Ideally, these systems should provide the full control of such data to the respective owner. In spite of this importance, most of the works focus more on describing how blockchain models can be used in a PHR scenario rather than whether these models are in fact feasible and robust enough to support a large number of users., Objective: To achieve a consistent, reproducible, and comparable PHR system, we build a novel ledger-oriented architecture out of a permissioned distributed network, providing patients with a manner to securely collect, store, share, and manage their health data. We also emphasize the importance of suitable ledgers and smart contracts to operate the blockchain network as well as discuss the necessity of standardizing evaluation metrics to compare related (net)works., Methods: We adopted the Hyperledger Fabric platform to implement our blockchain-based architecture design and the Hyperledger Caliper framework to provide a detailed assessment of our system: first, under workload, ranging from 100 to 2500 simultaneous record submissions, and second, increasing the network size from 3 to 13 peers. In both experiments, we used throughput and average latency as the primary metrics. We also created a health database, a cryptographic unit, and a server to complement the blockchain network., Results: With a 3-peer network, smart contracts that write on the ledger have throughputs, measured in transactions per second (tps) in an order of magnitude close to 10 2 tps, while those contracts that only read have rates close to 10 3 tps. Smart contracts that write also have latencies, measured in seconds, in an order of magnitude close to 10 1 seconds, while that only read have delays close to 10 0 seconds. In particular, smart contracts that retrieve, list, and view history have throughputs varying, respectively, from 1100 tps to 1300 tps, 650 tps to 750 tps, and 850 tps to 950 tps, impacting the overall system response if they are equally requested under the same workload. Varying the network size and applying an equal fixed load, in turn, writing throughputs go from 10 2 tps to 10 1 tps and latencies go from 10 1 seconds to 10 2 seconds, while reading ones maintain similar values., Conclusions: To the best of our knowledge, we are the first to evaluate, using Hyperledger Caliper, the performance of a PHR blockchain architecture and the first to evaluate each smart contract separately. Nevertheless, blockchain systems achieve performances far below what the traditional distributed databases achieve, indicating that the assessment of blockchain solutions for PHR is a major concern to be addressed before putting them into a real production., (©Thiago Bulhões da Silva Costa, Lucas Shinoda, Ramon Alfredo Moreno, Jose E Krieger, Marco Gutierrez. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.04.2022.)

Objective: To describe the prevalence of sexual dysfunction in a group of pregnant women, and to explore potential factors associated with this condition in this population., Material and Methods: Descriptive cross-sectional study in pregnant women 15 years of age and older, sexually active during gestation, receiving prenatal care at the San Juan de Dios Hospital in Rionegro between January and March, 2021. The exclusion criteria were patients with disabilities or cognitive impairment, or classified as having a mental disorder according to the World Health Organization (WHO); pregnant women with chronic, placental, ovulation, hemorrhagic or infectious conditions; and patients whose pregnancy was the result of sexual assault. The Female Sexual Function Index (FSFI) questionnaire was applied, and sociodemographic and sexual and reproductive health variables were measured. Results are expressed as absolute and relative frequencies for qualitative variables, and as medians and interquartile ranges for quantitative variables., Results: The mean age in years was 27.5 (IQR: 21.3-31.0) and the mean gestational age was 28.5 weeks (IQR: 21.3-34.8). After administering the FSFI, it was found that 37 women (37.7%) had sexual dysfunction (score < 26.5). The median scores for the participants without sexual dysfunction and those with sexual dysfunction were 29.4 (IQR 26.8-32) and 22.3 (IQR 20-24), respectively. The mean scores for each domain were: desire 3.6 (IQR: 3.0-4.2); arousal 4.5 (IQR: 3.6-5.1); lubrication 4.8 (IQR: 3.9-5.4); orgasm 4.4 (IQR: 3.6-5.2); pain 4.4 (IQR: 3.6-6.0); and satisfaction 5.4 (IQR: 4.8-6.0). The total score (p<0.05) was better in older women and those with one or more children., Conclusion: Sexual dysfunction occurs at least in one third of pregnant women, especially during the third trimester. Sexual dysfunction should be considered in daily clinical practice, given that approaching the topic from an education perspective can help reduce a problem that affects the couple and quality of life. It is critical to undertake additional research that includes assessment of the effectiveness and safety of educational strategies in this population with sexual dysfunction., (Copyright (c) 2021 Revista Colombiana de Obstetricia y Ginecología)

Latitudinal diversity gradients (LDG) and their explanatory factors are among the most challenging topics in macroecology and biogeography. Despite of its apparent generality, a growing body of evidence shows that 'anomalous' LDG ( i.e ., inverse or hump-shaped trends) are common among marine organisms along the Southeastern Pacific (SEP) coast. Here, we evaluate the shape of the LDG of marine benthic polychaetes and its underlying causes using a dataset of 643 species inhabiting the continental shelf (<200 m depth), using latitudinal bands with a spatial resolution of 0.5°, along the SEP (3-56° S). The explanatory value of six oceanographic (Sea Surface Temperature (SST), SST range, salinity, salinity range, primary productivity and shelf area), and one macroecological proxy (median latitudinal range of species) were assessed using a random forest model. The taxonomic structure was used to estimate the degree of niche conservatism of predictor variables and to estimate latitudinal trends in phylogenetic diversity, based on three indices (phylogenetic richness (PD SES ), mean pairwise distance (MPD SES ), and variation of pairwise distances (VPD)). The LDG exhibits a hump-shaped trend, with a maximum peak of species richness at ca. 42° S, declining towards northern and southern areas of SEP. The latitudinal pattern was also evident in local samples controlled by sampling effort. The random forest model had a high accuracy (pseudo-r 2 = 0.95) and showed that the LDG could be explained by four variables (median latitudinal range, SST, salinity, and SST range), yet the functional relationship between species richness and these predictors was variable. A significant degree of phylogenetic conservatism was detected for the median latitudinal range and SST. PD SES increased toward the southern region, whereas VPD showed the opposite trend, both statistically significant. MPD SES has the same trend as PD SES , but it is not significant. Our results reinforce the idea that the south Chile fjord area, particularly the Chiloé region, was likely the evolutionary source of new species of marine polychaetes along SEP, creating a hotspot of diversity. Therefore, in the same way as the canonical LDG shows a decline in diversity while moving away from the tropics; on this case the decline occurs while moving away from Chiloé Island. These results, coupled with a strong phylogenetic signal of the main predictor variables suggest that processes operating mainly at evolutionary timescales govern the LDG., Competing Interests: Nicolás Rozbaczylo is employed by FAUNAMAR Ltda., (© 2021 Moreno et al.)

Background: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy ( 1 H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD., Objective: To investigate whether CA severity is associated with changes in anterior cingulate cortex (ACC) neurometabolite profile in BD and HC subjects., Methods: Fifty-nine BD I euthymic patients and fifty-nine HC subjects were assessed using the Childhood Trauma Questionnaire (CTQ) and underwent a 3-Tesla 1 H-MRS scan. Severity of childhood abuse (physical, sexual and emotional) and its association with levels of brain metabolites was analyzed within each group., Results: BD patients had higher total scores on the CTQ and higher severity rates of sexual and physical abuse compared to HC subjects. Greater severity of physical and sexual abuse was associated with increased ACC PCr level and lower Cr/PCr ratio in the BD group only., Conclusion: Sexual and physical abuse in BD patients, but not in HC subjects, appeared to be associated with creatine metabolism in the ACC, which can influence neuronal mitochondrial energy production. Further studies should investigate whether this is the mechanism underlying the association between CA and worse clinical outcomes in BD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the pharmacokinetics and pharmacodynamics of oestriol (E3) and trimegestone (TMG) in healthy women after application of three different vaginal rings over 21 days. The vaginal rings had a nominal delivery rate of 0.413/0.050 mg/day (Test 1), 0.311/0.090 mg/day (Test 2) and 0.209/0.137 mg/day (Test 3) E3/TMG., Methods: Thirty-five healthy women were randomised to receive a single application of Test 1, 2 or 3 (Clinical Trial NCT03343912). The E3 and TMG plasma concentration was determined by LC-MS/MS. Oestradiol (E2) and progesterone (PG) serum concentrations, and bleeding patern were determined as pharmacodynamic parameters. Safety was assessed by evaluation of adverse events and local tolerability., Results: The total and maximum exposure of E3 and TMG increased in a proportional ratio to dose. However, not in a magnitude which was expected from the dose differences for E3. During Test 2 and 3 treatment all E2 and PG values remained on a well suppressed level until end of treatment. E2 and PG serum levels increased distinctly earlier after ring removal with Test 1 compared to Test 2 and 3. Test 3 achieved 95.24% of "no bleeding" days under treatment followed by Test 1 (91.67%), and Test 2 (86.15%)., Conclusions: The Test 3 formulation presented the best dose combination of E3/TMG for contraception. Moreover, all vaginal rings were well tolerated.

Background: Mood disorders are the most frequent psychiatric disorders in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). The pathophysiological mechanisms in common between TLE and mood disorders include abnormalities in the serotonergic pathway. We aimed to evaluate the association between serotonin transporter genetic polymorphisms - 5-HTTLPR and 5-HTTVNTR - and the presence of mood disorders in patients with TLE-HS., Methods: We evaluated 119 patients with TLE-HS, with and without psychiatric disorder; 146 patients diagnosed with major depressive disorder (MDD), and 113 healthy volunteers. Individuals were genotyped for the 5-HTTLPR and 5-HTTVNTR polymorphisms., Results: No difference was observed between the TLE-HS groups, healthy controls, and MDD without epilepsy. There was a correlation between the 12-allele of the 5-HTTVNTR and the family history of patients with epilepsy with TLE-HS (p = 0.013)., Conclusions: In this study conducted in two Brazilian centers, the serotonin transporter polymorphisms evaluated cannot be associated with depressive disorder in patients with TLE-HS. Still, they do have some influence over some clinical characteristics of epilepsy in TLE-HS. These data may not be reproduced in other populations with distinct ethnic characteristics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

COVID-19 is a highly contagious disease that can cause severe pneumonia. Patients with pneumonia undergo chest X-rays (XR) to assess infiltrates that identify the infection. However, the radiographic characteristics of COVID-19 are similar to the other acute respiratory syndromes, hindering the imaging diagnosis. In this work, we proposed identifying quantitative/radiomic biomarkers for COVID-19 to support XR assessment of acute respiratory diseases. This retrospective study used different cohorts of 227 patients diagnosed with pneumonia; 49 of them had COVID-19. Automatically segmented images were characterized by 558 quantitative features, including gray-level histogram and matrices of co-occurrence, run-length, size zone, dependence, and neighboring gray-tone difference. Higher-order features were also calculated after applying square and wavelet transforms. Mann-Whitney U test assessed the diagnostic performance of the features, and the log-rank test assessed the prognostic value to predict Kaplan-Meier curves of overall and deterioration-free survival. Statistical analysis identified 51 independently validated radiomic features associated with COVID-19. Most of them were wavelet-transformed features; the highest performance was the small dependence matrix feature of "low gray-level emphasis" (area under the curve of 0.87, sensitivity of 0.85, [Formula: see text]). Six features presented short-term prognostic value to predict overall and deterioration-free survival. The features of histogram "mean absolute deviation" and size zone matrix "non-uniformity" yielded the highest differences on Kaplan-Meier curves with a hazard ratio of 3.20 ([Formula: see text]). The radiomic markers showed potential as quantitative measures correlated with the etiologic agent of acute infectious diseases and to stratify short-term risk of COVID-19 patients., (© 2021. Society for Imaging Informatics in Medicine.)

Knowledge of functional neuroanatomy is essential to design the most appropriate clinical functional MR imaging (fMR imaging) paradigms and to properly interpret fMR imaging study results. The correlation between neuroanatomy and brain function is also useful in general radiologic practice, as it improves the radiologist's ability to read routine brain examinations. Functional MR imaging is used primarily to determine the areas involved in functioning of movements, speech, and vision. Preoperative fMR imaging findings also play a key role in the neurosurgeon's decision to perform a biopsy, a subtotal resection, or a maximal resection using awake craniotomy., Competing Interests: Disclosure R.A. Moreno has nothing to disclose. A.I. Holodny is the Owner/President of fMR imaging Consultants, LLC, a purely educational entity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The contractions of Chelonoidis carbonaria aortic rings induced by electrical field stimulation (EFS) are not inhibited by blockade of the voltage-gated sodium channels by tetrodotoxin but almost abolished by the α1/α2-adrenoceptor antagonist phentolamine. The objective of this study was to identify the mediator(s) responsible for the EFS-induced contractions of Chelonoidis carbonaria aortic rings. Each ring was suspended between two wire hooks and mounted in isolated 10 ml organ chambers filled with oxygenated and heated Krebs-Henseleit's solution. Dopamine, noradrenaline and adrenaline concentrations were analysed by liquid chromatography coupled to tandem mass spectrometry. The contractions caused by dopamine and EFS were done in absence and presence of the nitric oxide (NO) synthesis inhibitor L-NAME, the NO-sensitive guanylyl cyclase inhibitor ODQ, the D1-like receptor antagonist SCH-23390, the D2-like receptor antagonists risperidone, quetiapine, haloperidol, and the tyrosine hydroxylase inhibitors salsolinol and 3-iodo-L-tyrosine. Basal concentrations of dopamine, noradrenaline and adrenaline were detected in Krebs-Henseleit solution containing the aortic rings. The catecholamine concentrations were significantly reduced in endothelium-denuded aortic rings. L-NAME and ODQ significantly potentiated the dopamine-induced contractions. The D2-like receptor antagonists inhibited the EFS-induced contractions of the aortic rings treated with L-NAME, whereas SCH 23390 had no effect. Similar results were observed in the contractions induced by dopamine in L-NAME treated aortic rings. These results indicate that catecholamines released by endothelium regulate the EFS-induced contractions. This may constitute a suitable mechanism by which reptilia modulate specific organ blood flow distribution.This paper has an associated First Person interview with the first author of the article., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Pharmacokinetic parameters and efficacy prediction indexes (C max /MIC 90 and AUC 0-24 /MIC 90 ) of an enrofloxacin hydrochloride (ENR-HCl) veterinary product soluble in water were determined in healthy broiler chickens of both sexes after a single oral dose of ENR-HCl (equivalent to 10 mg ENR base/kg bw). Monte Carlo simulations targeting C max /MIC 90 = 10 and AUC 0-24 /MIC 90 =125 were also performed based on a set of MIC (minimum inhibitory concentration) values of bacterial strains that induce common clinical diseases in broiler chickens and that showed to be susceptible to ENR-HCl. Plasma concentrations of ENR and its main metabolite ciprofloxacin (CIP) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time curves were found to fit a non-compartmental open model. The ratio of the area under the plasma concentration-time curve (AUC) of CIP/ENR was 4.91%. Maximum plasma concentrations of 1.35 ± 0.15 μg/mL for ENR-HCl and 0.09 ± 0.01 μg/mL for CIP were reached at 4.00 ± 0.00 h and 3.44 ± 1.01 h, respectively. Areas under the plasma vs. time concentration curve in 24 h (AUC 0-24 ) were 18.91 ± 1.91 h × μg/mL and 1.19 ± 0.12 h × μg/mL for ENR-HCl and CIP, respectively. Using a microbroth dilution method, the minimum inhibitory concentration (MIC 90 ) values were determined for ENR-HCl for 10 bacterial strains ( Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonella ser. Enteritidis , Salmonella ser. Gallinarum , Salmonella ser. Pullorum, and Salmonella ser. Typhimurium), which are the most common causes of infectious clinical diseases in broiler chickens. In summary, the PK/PD ratios and Monte Carlo simulation were carried out for ENR-HCl in poultry, which due to its solubility was administered in drinking water. The PK/PD efficacy prediction indexes and Monte Carlo simulations indicated that the ENR-HCl oral dose used in this study is useful for bacterial infections in treating C. perfringens (Gram-positive), E. coli and S . ser. Enteritidis (Gram-negative) and M. gallisepticum bacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 μg/mL for E. coli and S . ser. Enteritidis and MIC ≤ 0.1 μg/mL for M. gallisepticum . For C. perfringens , the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation., Competing Interests: MM was employed by company AGRIAS Pesquisa & Desenvolvimento S.A.R.C. no Agronegócio Ltda., Amparo, Brazil. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bonassa, Miragliotta, Simas, Eberlin, Anadón, Moreno and Reyes.)