Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

Clozapine-Induced Eosinophilia: a Case Report.

INTRODUCTION: Clozapine is an atypical antipsychotic drug eligible for treatment-resistant schizophrenia. It frequently represents the best and the only choice in resistant schizophrenia. However, its use is feared by many professionals due to its possible adverse effects, such as eosinophilia. CASE REPORT: We report a case of a young white male suffering from treatment-resistant schizophrenia who rapidly developed eosinophilia after starting clozapine. DISCUSSION: We present a case of a 26-year-old white man diagnosed with schizophrenia with poor clinical response to several antipsychotics owing to which clozapine was started. Psychotic symptoms improved dramatically but a progressively ascendant eosinophilia was reported during serial haematological analyses. The patient remained physically asymptomatic. An exhaustive assessment with ancillary diagnostic tests revealed no cause for eosinophilia. Thus, a diagnosis of clozapine-induced eosinophilia was made. The drug was discontinued and eosinophil count progressively returned to normal but psychotic symptoms worsened. CONCLUSIONS: Clozapine treatment is frequently feared due to its possible side effects and complications, delaying its use in refractory schizophrenia. Also, to our knowledge, there are no specific guidelines on how to manage haematological side effects such as eosinophilia. This is problematic as, in some cases, it may lead to an unnecessary withdrawal of clozapine with a worsening of psychotic symptoms. We present a brief discussion of the recent literature on the subject.

Clozapine-Induced Eosinophilia: a Case Report

Introduction: Clozapine is an atypical antipsychotic drug eligible for treatment-resistant schizophrenia. It frequently represents the best and the only choice in resistant schizophrenia. However, its use is feared by many professionals due to its possible adverse effects, such as eosinophilia. Case report: We report a case of a young white male suffering from treatment-resistant schizophrenia who rapidly developed eosinophilia after starting clozapine. Discussion: We present a case of a 26-year-old white man diagnosed with schizophrenia with poor clinical response to several antipsychotics owing to which clozapine was started. Psychotic symptoms improved dramatically but a progressively ascendant eosinophilia was reported during serial haematological analyses. The patient remained physically asymptomatic. An exhaustive assessment with ancillary diagnostic tests revealed no cause for eosinophilia. Thus, a diagnosis of clozapine-induced eosinophilia was made. The drug was discontinued and eosinophil count progressively returned to normal but psychotic symptoms worsened. Conclusions: Clozapine treatment is frequently feared due to its possible side effects and complications, delaying its use in refractory schizophrenia. Also, to our knowledge, there are no specific guidelines on how to manage haematological side effects such as eosinophilia. This is problematic as, in some cases, it may lead to an unnecessary withdrawal of clozapine with a worsening of psychotic symptoms. We present a brief discussion of the recent literature on the subject.

Introducción: La clozapina es un fármaco antipsicótico atípico eligible para la esquizofrenia resistente al tratamiento. Con frecuencia representa la mejor y la única opción para la esquizofrenia resistente. Sin embargo, muchos profesionales temen utilizarla por sus posibles efectos adversos, como la eosinofilia. Reporte de caso: Se expone el caso de un joven blanco que sufre esquizofrenia resistente al tratamiento y desarrolló eosinofilia rápidamente tras comenzar el tratamiento con clozapina. Discusión: Varón de 26 años con diagnóstico de esquizofrenia y mala respuesta clínica a varios antipsicóticos, por lo que se inició clozapina. Los síntomas psicóticos mejoraron drásticamente, pero los análisis hematológicos seriados informaron una eosinofilia en ascenso progresivo. El paciente permaneció físicamente asintomático. Una evaluación exhaustiva con pruebas de diagnóstico complementarias no reveló ninguna causa de eosinofilia. Por lo tanto, se diagnosticó eosinofilia inducida por clozapina. Se suspendió el fármaco, el recuento de eosinófilos volvió progresivamente a la normalidad, pero los síntomas psicóticos empeoraron. Conclusiones: A menudo se teme tratar con clozapina por sus posibles efectos secundarios y sus complicaciones, lo cual retrasa su uso en la esquizofrenia refractaria. Además, hasta donde sabemos, no existen pautas específicas sobre cómo tratar los efectos secundarios hematológicos como la eosinofilia. Esto es problemático porque, en algunos casos, puede conducir a suspender innecesariamente la clozapina y que empeoren los síntomas psicóticos. Se presenta una breve discusión de la literatura reciente sobre el tema.

Ove hurts. An old cliché reborn a propos of a clinical case / Dolores de amor. Un cliché renacido a propósito de un caso clínico

Introduction: The spectrum of sexually motivated behaviors is extremely wide, including behaviors that are not biologically reprductive and hold exclusively ludic functions. We refer to the persistent and recurrent patterns of sexual arousal resulting from the exposure to non-normative sexual stimuli as paraphilias, and they are paradigmatic of the broad heterogeneity of human sexuality. Among these, paraphilic infantilism was first reported in the scientific literature by Tuchman and Lachman in 1964. It is characterized by the presence of sexual arousal or pleasure when playing childhood roles or using objects proper of childhood.Objective: We intend to describe a clinical case, with a focus on the atypical profile of sexual interests and behaviors comprising paraphilic infantilism and sadomasochism phenomena. We also seek to discuss the understanding of these phenomena in the context of the global clinical picture, their nosological framework, and their implication in the psychotherapeutic process.Methodology: In this study, we present the clinical case of a patient observed in the outpatient clinic of the first author. A targeted literature review was carried out through a bibliographic search in the PubMed database and a selection of reference works in the Sexology field. These data provided a basis from which we develop our clinical discussion of the case.Results: This article illustrates the case of a patient referred for psychotherapeutic intervention due to an anxious-depressive syndrome. During follow-up, a cluster of sexual behaviors was observed that involved preferential sexual interest for role-playing as a baby, and practices that involved physical suffering, dominance and submission. Conclusions: Paraphilia is a controversial clinical category...(AU)

Introducción: El espectro de conductas con motivación sexual es muy amplio, abarcando conductas que no son biológicamente reproductivas y que sostienen funciones exclusivamente lúdicas. Se denominan parafilias a los patrones persistentes y recurrentes de excitación sexual resultante de la exposición a estímulos sexuales no normativos, y su existencia resulta paradigmática de la amplia heterogeneidad de la sexualidad humana. Entre ellas, el Infantilismo parafílico fue descrito por primera vez en la literatura científica Tuchman y Lachman en 1964 y se caracteriza por obtener excitación o placer sexual a través de la representación de roles infantiles o del uso de objetos propios de la infancia. Objetivo: Nos proponemos describir un caso clínico, enfocando el perfil atípico de intereses y conductas sexuales que comprenden fenómenos de Infantilismo parafílico y Sadomasoquismo. Pretendemos discutir la comprensión de estos fenómenos en el contexto del cuadro clínico global, su marco nosológico y su implicación en el proceso psicoterapéutico. Metodología: Se relata el caso clínico de una paciente observada en el ámbito de la consulta de la primera autora. Se realiza una revisión no sistemática de la literatura científica a través de una búsqueda bibliográfica en la base de datos Pubmed y de la consulta de obras de referencia en el área de la Sexología. Se procede a la discusión clínica, basada en los datos presentados. Resultados: Este artículo ilustra el caso de una paciente, derivada a intervención psicoterapéutica por síndrome ansioso-depresivo. Durante el acompañamiento, se identificó un patrón de respuesta sexual caracterizado por un interés sexual preferencial en representar el rol de un bebé y prácticas que implicaban sufrimiento físico, dominación y sumisión. Conclusiones: La Parafilia es una entidad clínica controvertida...(AU)

Intrapartum care policies in high-income countries with a universal health system: A scoping review.

Evidence-based and sustainable intrapartum care policies are essential for safer, effective, and positive birth experiences. This scoping review aimed to map intrapartum care policies for pregnant women at low-risk of complications, in high-income countries with a universal health system. The study followed Joanna Briggs Institute methodology for scoping reviews and PRISMA-ScR. Search was conducted on CINAHL-EBSCO, Scopus, MEDLINE-Pubmed, Cochrane Central Register of Controlled Trials-EBSCO, and, Academic Search Complete-EBSCO. Grey literature was searched, references screened and experts contacted for additional studies/policies. Data were extracted/analysed by two independent reviewers and results were presented in tabular and narrative format. The concept was governmental intrapartum care policies, the context were OECD high-income countries with a health-financing system founded on the Beveridge Model and the participants were low-risk pregnant women From the 561 records screened, 22 were selected, concerning intrapartum care policies from Australia, Denmark, Spain, Finland, Portugal, and the United Kingdom. All the included records were retrieved in the grey literature. No intrapartum care governmental policies were found for Greece, Iceland, Italy, New Zealand, Norway, and Sweden. Some countries do not refer to all the analysed care aspects and there are differences in detail, depth, range, and scientific. The policies show general similarities but differ in the timing and the content of the recommended intrapartum care. Not all of the analysed countries have intrapartum care policies and those who have shown differences between recommendations. These results can be used to create/revise intrapartum care policies.

Knowledge of cytomegalovirus and available prevention strategies in pregnancy: a cross-sectional study in Portugal.

OBJECTIVE: Maternal and fetal congenital infection by cytomegalovirus (CMV) during pregnancy is the leading infectious cause of neurologic impairment and hearing loss. Efforts at limiting CMV exposure are based on hygienic measures. This study assessed the relationship between CMV knowledge and pregnant women's time perspective as per the Zimbardo Time Perspective Inventory (ZTPI) scale. METHODS: We conducted a prospective descriptive study at a secondary-care Portuguese hospital between October to November 2021. All consecutive pregnant women in antenatal third-trimester appointments were included. The questionnaire included: sociodemographic data, knowledge about CMV, and the ZTPI scale, validated to our population. The number of correct answers in the knowledge section of the questionnaire was tallied to determine the individual knowledge score (KS). We investigated patients subjective perceptions of CMV infection during pregnancy, CMV knowledge, and CMV serologic status of pregnant women. RESULTS: We enrolled 96 pregnant women. 81.0% had not previously heard about CMV and only 8.8% had heard about it through their obstetrician. No significant association between awareness of CMV and education level was detected. 16.0% of pregnant women declared that they were aware of the hygienic measures for CMV. The CMV serology was performed in 21.3% of those enrolled in the preconception assessment, and 13.8% proved to be immune. From the time perspective, half of the women displayed a future-oriented attitude. Future-oriented women had significantly higher KS. No significant association was found between KS and education level, age, or previous pregnancy. There was a significant association between KS and women that work in health care. CONCLUSIONS: Most patients had no knowledge of CMV. Being a medical professional and having a future-oriented outlook increases knowledge about CMV. Primary health care and obstetrics doctors may play a crucial role in informing pregnant women of antenatal appointments. The CMV serology coverage is scarce in this sample. This study constitutes a first step toward raising the awareness of the general population about CMV.

Evaluation of right ventricle systolic function after tetralogy of Fallot repair: A systematic review comparing cardiac magnetic resonance and global longitudinal strain.

BACKGROUND: Most patients who undergo tetralogy of Fallot (TOF) repair experience late right ventricle (RV) dysfunction due to pulmonary valve regurgitation (PVR). Cardiac magnetic resonance (CMR) is the gold standard method for evaluating RV during follow-up. Global longitudinal strain (GLS) has been introduced as a novel method for the assessment of RV dysfunction. We aimed to compare the feasibility of GLS and CMR for assessing RV function after TOF repair. METHODS: We systematically reviewed the English literature using PubMed, SciELO and Google Scholar for articles published between January 1, 2015, and December 31, 2020. Articles evaluating RV function comparing by GLS and CMR after TOF repair were included. RESULTS: Nine studies including 465 patients were analyzed. Most patients were men (280; 60%), the male:female ratio was 1.5:1, and the age range was .8 to 57.7 years. The mean follow-up time was 6 to 32 months. The correlation between RV GLS and RV ejection fraction (EF) by CMR was negative for the articles and varied from moderate to strong (r = -.45, r = -.60, r = -.76). CONCLUSION: Right ventricle GLS can be considered for routine follow-up of TOF repair patients, even though CMR remains the noninvasive gold standard method. Using a single parameter may not allow comparison of the accuracy of 3D RV EF by using CMR and GLS. Further studies with a larger number of patients undergoing TOF repair are required to evaluate the correlation between these examinations.

Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.

The unique environment of the brain and retina is tightly regulated by blood-brain barrier and the blood-retinal barrier, respectively, to ensure proper neuronal function. Endothelial cells within these tissues possess distinct properties that allow for controlled passage of solutes and fluids. Pericytes, glia cells and neurons signal to endothelial cells (ECs) to form and maintain the barriers and control blood flow, helping to create the neurovascular unit. This barrier is lost in a wide range of diseases affecting the central nervous system (CNS) and retina such as brain tumors, stroke, dementia, and in the eye, diabetic retinopathy, retinal vein occlusions and age-related macular degeneration to name prominent examples. Recent studies directly link barrier changes to promotion of disease pathology and degradation of neuronal function. Understanding how these barriers form and how to restore these barriers in disease provides an important point for therapeutic intervention. This review aims to describe the fundamentals of the blood-tissue barriers of the CNS and how the use of transgenic animal models led to our current understanding of the molecular framework of these barriers. The review also highlights examples of targeting barrier properties to protect neuronal function in disease states.

Zika-Related Microcephaly and Its Repercussions for the Urinary Tract: Clinical, Urodynamic, Scintigraphic and Radiological Aspects.

AIMS: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. METHODS: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson's chi-squared test or Fisher's exact test. RESULTS: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. CONCLUSIONS: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.

Thrombolytic tPA-induced hemorrhagic transformation of ischemic stroke is mediated by PKCß phosphorylation of occludin.

The current standard of care for moderate to severe ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA). Treatment with tPA can significantly improve neurologic outcomes; however, thrombolytic therapy is associated with an increased risk of intracerebral hemorrhage (ICH). The risk of hemorrhage significantly limits the use of thrombolytic therapy, and identifying pathways induced by tPA that increase this risk could provide new therapeutic options to extend thrombolytic therapy to a wider patient population. Here, we investigate the role of protein kinase Cß (PKCß) phosphorylation of the tight junction protein occludin during ischemic stroke and its role in cerebrovascular permeability. We show that activation of this pathway by tPA is associated with an increased risk of ICH. Middle cerebral artery occlusion (MCAO) increased phosphorylation of occludin serine 490 (S490) in the ischemic penumbra in a tPA-dependent manner, as tPA-/- mice were significantly protected from MCAO-induced occludin phosphorylation. Intraventricular injection of tPA in the absence of ischemia was sufficient to induce occludin phosphorylation and vascular permeability in a PKCß-dependent manner. Blocking occludin phosphorylation, either by targeted expression of a non-phosphorylatable form of occludin (S490A) or by pharmacologic inhibition of PKCß, reduced MCAO-induced permeability and improved functional outcome. Furthermore, inhibiting PKCß after MCAO prevented ICH associated with delayed thrombolysis. These results show that PKCß phosphorylation of occludin is a downstream mediator of tPA-induced cerebrovascular permeability and suggest that PKCß inhibitors could improve stroke outcome and prevent ICH associated with delayed thrombolysis, potentially extending the window for thrombolytic therapy in stroke.

Antenatal care policy in high-income countries with a universal health system: A scoping review.

The availability, effectiveness, and access to antenatal care are directly linked with good maternal and neonatal outcomes, making antenatal care an important determinant in health. But to be effective, care must always be appropriate, not excessive, not insufficient. Perinatal outcomes vary within and between countries, raising questions about practices, the use of best evidence in clinical decisions and the existence of clear and updated guidance. Through a scoping review methodology, this study aimed to map the available antenatal care policies for low-risk pregnant women in high-income countries with a universal health system, financed by the government through tax payments. Following searches on the main databases and grey literature, the authors identified and analysed ten antenatal care policies using a previously piloted datachart: Australia, Denmark, Finland, Iceland, Italy, Norway, Portugal, Spain, Sweden and the United Kingdom. Some policies were over 10 years old, some recommendations did not present a rationale or context, others were outdated, or were simply different approaches in the absence of strong evidence. Whilst some recommendations were ubiquitous, others differed either in the recommendation provided, the timing, or the frequency. Similarly, we found wide variation in the methods/strategy used to support the recommendations provided. These results confirm that best evidence is not always assimilated into policies and clinical guidance. Further research crossing these differences with perinatal outcomes and evaluation of cost could be valuable to optimise guidance on antenatal care. Similarly, some aspects of care need further rigorous studies to obtain evidence of higher quality to inform recommendations.

Anomic aphasia after COVID-19 infection: a case report.

Purpose: This case reports on anomic aphasia related to COVID-19. Increasing knowledge about rare symptoms and complications may aid in the characterization of the disease, understand its pathophysiology, identify more quickly possible infected people and break the transmission chain. Case description: This work reports on the case of a middle-aged man who presented to his assistant psychiatrist complaining about difficulty with naming objects in his daily routine surroundings, with ten weeks of duration and following a SARS-CoV-2 infection. The organic study, including brain magnetic resonance imaging, was unremarkable. The symptoms resolved spontaneously within fourteen weeks. Comment: Neurological manifestations of COVID-19 may be related to the dysfunction of the blood-brain barrier, resulting in immune cell infiltration and neuroinflammation that can persist for weeks or months after the resolution of the infection. Weakened health after overcoming the infection acute phase is being reported increasingly and called post-COVID-syndrome. Rare disorders such anomic aphasia can occur in this syndrome.

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing.

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients' bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment.

Clozapine-Induced Eosinophilia: a Case Report.

INTRODUCTION: Clozapine is an atypical antipsychotic drug eligible for treatment-resistant schizophrenia. It frequently represents the best and the only choice in resistant schizophrenia. However, its use is feared by many professionals due to its possible adverse effects, such as eosinophilia. CASE REPORT: We report a case of a young white male suffering from treatment-resistant schizophrenia who rapidly developed eosinophilia after starting clozapine. DISCUSSION: We present a case of a 26-year-old white man diagnosed with schizophrenia with poor clinical response to several antipsychotics owing to which clozapine was started. Psychotic symptoms improved dramatically but a progressively ascendant eosinophilia was reported during serial haematological analyses. The patient remained physically asymptomatic. An exhaustive assessment with ancillary diagnostic tests revealed no cause for eosinophilia. Thus, a diagnosis of clozapine-induced eosinophilia was made. The drug was discontinued and eosinophil count progressively returned to normal but psychotic symptoms worsened. CONCLUSIONS: Clozapine treatment is frequently feared due to its possible side effects and complications, delaying its use in refractory schizophrenia. Also, to our knowledge, there are no specific guidelines on how to manage haematological side effects such as eosinophilia. This is problematic as, in some cases, it may lead to an unnecessary withdrawal of clozapine with a worsening of psychotic symptoms. We present a brief discussion of the recent literature on the subject.

Nonpharmacological interventions used in the perioperative period to prevent anxiety in adolescents: a scoping review.

OBJECTIVE: The objective of this scoping review was to examine and map the range of nonpharmacological interventions used in the perioperative period to prevent anxiety in adolescents. INTRODUCTION: Undergoing surgery involves experiencing fears and uncertainties that lead to an increase in anxiety levels. The interventions used to prevent anxiety in the perioperative period in adolescents must be appropriate to their developmental stage. INCLUSION CRITERIA: Studies involving adolescents (10 to 19 years of age) undergoing any type of surgical procedure and specifying any nonpharmacological interventions administered to prevent anxiety, implemented in the perioperative period, were included in this review. METHODS: A comprehensive search strategy using multiple databases was employed to find relevant studies. The databases search included MEDLINE via PubMed; CINAHL Plus with Full Text via EBSCO; Cochrane Central Register of Controlled Trials; LILACS; Scopus; Library, Information Science and Technology Abstracts; PsycINFO; JBI Connect+; and Cochrane Database of Systematic Reviews. Sources of unpublished studies and gray literature were TDX - Tesis Doctorals en Xarxa (Spain); RCAAP - Repositório Científico de Acesso Aberto de Portugal; OpenGrey - System for Information on Grey Literature in Europe; and MedNar. Studies published in English, Spanish, or Portuguese were included. There was no date restriction, or geographical or cultural limitation applied to the search. The relevant studies and their reported outcomes were organized and analyzed. RESULTS: The database search yielded 1438 articles, and three additional records were added after hand searching. Title, abstract, and full-text review identified 11 papers that met the inclusion criteria. The final data set represented 947 participants. The data were analyzed according to the type of nonpharmacological intervention, population, concept (outcome measured and tool used), context (physical location; preoperative vs. postoperative), frequency and duration of the intervention, and which professional team member implemented the intervention. Eight nonpharmacological interventions were identified, applied either in the preoperative or postoperative context. The nurses were the main professionals administering the nonpharmacological interventions to the adolescents. CONCLUSIONS: A variety of nonpharmacological interventions were used in the perioperative period to prevent anxiety in adolescents. The most common interventions were music/musicotherapy and hypnosis/guided imagery. However, other interventions such as therapeutic play, preoperative preparation program, mothers' presence during the anesthesia induction, distraction, relaxation training, massage therapy, and reading were also identified. These interventions were used alone or in a combination of two interventions, either preoperatively or postoperatively. The adolescents in the early stage (10 to 14 years) were the most studied group and the adolescents in the late stage (17 to 19 years) were the least studied. Future research should focus on the implementation of nonpharmacological interventions in the perioperative period involving adolescents, particularly late adolescents. A systematic review on the effect of nonpharmacological interventions for anxiety management in adolescents in the perioperative period should be conducted. SCOPING REVIEW REGISTRATION: Open Science Framework: https://osf.io/jhwca/.

Vascular Expression of Permeability-Resistant Occludin Mutant Preserves Visual Function in Diabetes.

Diabetic retinopathy is one of the leading causes of vision loss and blindness. Extensive preclinical and clinical evidence exists for both vascular and neuronal pathology. However, the relationship of these changes in the neurovascular unit and impact on vision remains to be determined. Here, we investigate the role of tight junction protein occludin phosphorylation at S490 in modulating barrier properties and its impact on visual function. Conditional vascular expression of the phosphorylation-resistant Ser490 to Ala (S490A) form of occludin preserved tight junction organization and reduced vascular endothelial growth factor (VEGF)-induced permeability and edema formation after intraocular injection. In the retinas of streptozotocin-induced diabetic mice, endothelial-specific expression of the S490A form of occludin completely prevented diabetes-induced permeability to labeled dextran and inhibited leukostasis. Importantly, vascular-specific expression of the occludin mutant completely blocked the diabetes-induced decrease in visual acuity and contrast sensitivity. Together, these results reveal that occludin acts to regulate barrier properties downstream of VEGF in a phosphorylation-dependent manner and that loss of inner blood-retinal barrier integrity induced by diabetes contributes to vision loss.

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.

Surgical findings in cryptorchidism in children with Zika-related microcephaly: a case series.

BACKGROUND: Complications in the urinary tract related to congenital Zika syndrome have recently been reported. One complication, cryptorchidism, has been reported by the Microcephaly Epidemic Research Group/MERG, in Pernambuco/Brazil. The present article describes for the first time the surgical findings in a case series of boys with Zika-related microcephaly and cryptorchidism, who underwent surgical testicular exploration as a contribution to better understand the possible mechanisms involved in gonads formation and descent. METHODS: A total of 7 children (11 testicular units), aged 3 to 4 years, were submitted to inguinal or scrotal orchidopexy for the treatment of palpable cryptorchidism between August 2019 and January 2020. Characteristics of the gonads and its annexes related to appendixes, testis-epididymis dissociation, gubernacular insertion, and associated hydroceles and/or hernias were described. Measures in centimetres were taken for volume calculate. RESULTS: We found a low prevalence of testicular and epididymal appendix (66.7%), a high prevalence of testis-epididymis dissociation (55.6%), low mean testicular volume for their ages (lower for older boys) and ectopic gubernacular insertion in all cases. There was no evidence of associated hydroceles and/or hernias in any case. No surgical complication was registered or reported, and all explored gonads were properly placed in the scrotal sac. CONCLUSIONS: We herein describe the surgical findings of these children's orchidopexies and discuss the possible mechanisms of viral action in embryogenesis and postnatal growth and development of the testes and annexes. These children need to be followed over time due to the higher risk of testicular atrophy and malignancy. Surgical timing seems to be relevant to avoid loss of testicular volume.