The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

Spontaneous Remission of High-Grade Non-Hodgkin Lymphoma After SARS-CoV-2 Infection: A Case Report.

ABSTRACT: Despite extensive research into COVID-19 since its emergence in late 2019, there is still much not fully understood about its long-term effects. When infected with SARS-CoV-2, cancer patients have been reported to be at higher risk for unfavorable outcomes. Nevertheless, evidence suggests that viruses may exhibit an antitumor effect in some cases, which has recently been anecdotally reported with SARS-CoV-2. We present the case of a patient with a recent high-grade non-Hodgkin lymphoma diagnosis and without any cancer-specific therapy, in whom a complete metabolic response on 2-[ 18 F]FDG PET/CT was observed after COVID-19.

Beyond the Bones: A Case Report of Extraosseous Ewing Sarcoma.

Ewing sarcoma (ES) is primarily recognized as a primary bone tumor; however, its extraosseous variant is exceptionally rare and presents unique clinical challenges. In this article, we report the case of a 22-year-old male who initially presented with abdominal swelling. Diagnostic tests included abdominal imaging and a CT scan, revealing a solid liver mass. A thorough evaluation confirmed it to be an extraosseous ES, supported by liver biopsy and immunohistochemistry demonstrating positive expression for AE1/AE3 and CD-99, along with genetic analysis revealing a rearrangement of the EWSR1 gene (translocation 22q12). The patient's treatment involved a multimodal approach, including perioperative chemotherapy, surgery, and postoperative chemotherapy, following which the patient remained in complete remission after 24 months. This case emphasizes the importance of considering rare malignancies such as ES in differential diagnoses for young patients with liver masses. It also accentuates the pivotal role of family physicians in early detection and holistic patient care, underscoring the need for comprehensive investigations when encountering persistent symptoms.

Triple Therapy for Cystic Fibrosis (Elexacaftor, Tezacaftor, and Ivacaftor): Desensitization After Skin Rash.

Cystic fibrosis (CF) is an autosomal recessive disorder of the CF transmembrane conductance regulator (CFTR) gene. CFTR modulators are novel approved therapies, and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the current gold standard for patients with at least one F508del mutation. CFTR modulators are usually well-tolerated, but some adverse effects may occur, including skin rash. We report a case of a female patient who developed a severe skin rash after initiating treatment with ELX/TEZ/IVA. Modulator therapy and contraception were discontinued, and consequently, there was a drop in lung function and reappearance of respiratory symptoms. After rash resolution, a gradual reintroduction of ELX/TEZ/IVA was started, and this is the protocol the authors have summarized. Triple therapy with CFTR modulators has a significant impact on lung function and the quality of life of CF patients who have at least one F508del mutation, justifying its reintroduction and desensitization even after a severe adverse effect.

Nanofiber Carriers of Therapeutic Load: Current Trends.

The fast advancement in nanotechnology has prompted the improvement of numerous methods for the creation of various nanoscale composites of which nanofibers have gotten extensive consideration. Nanofibers are polymeric/composite fibers which have a nanoscale diameter. They vary in porous structure and have an extensive area. Material choice is of crucial importance for the assembly of nanofibers and their function as efficient drug and biomedicine carriers. A broad scope of active pharmaceutical ingredients can be incorporated within the nanofibers or bound to their surface. The ability to deliver small molecular drugs such as antibiotics or anticancer medications, proteins, peptides, cells, DNA and RNAs has led to the biomedical application in disease therapy and tissue engineering. Although nanofibers have shown incredible potential for drug and biomedicine applications, there are still difficulties which should be resolved before they can be utilized in clinical practice. This review intends to give an outline of the recent advances in nanofibers, contemplating the preparation methods, the therapeutic loading and release and the various therapeutic applications.

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

New Advances in Biomedical Application of Polymeric Micelles.

In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase the solubility and the stability of the encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because of their unique core-shell architecture. They are colloidal dispersions of amphiphilic compounds, which self-assemble in an aqueous medium, giving a structure-type core-shell, with a hydrophobic core (that can encapsulate hydrophobic drugs), and a hydrophilic shell, which works as a stabilizing agent. These features offer PMs adequate steric protection and determine their hydrophilicity, charge, length, and surface density properties. Furthermore, due to their small size, PMs can be absorbed by the intestinal mucosa with the drug, and they transport the drug in the bloodstream until the therapeutic target. Moreover, PMs improve the pharmacokinetic profile of the encapsulated drug, present high load capacity, and are synthesized by a reproducible, easy, and low-cost method. In silico approaches have been explored to improve the physicochemical properties of PMs. Based on this, a computer-aided strategy was developed and validated to enable the delivery of poorly soluble drugs and established critical physicochemical parameters to maximize drug loading, formulation stability, and tumor exposure. Poly(2-oxazoline) (POx)-based PMs display unprecedented high loading concerning water-insoluble drugs and over 60 drugs have been incorporated in POx PMs. Among various stimuli, pH and temperature are the most widely studied for enhanced drug release at the site of action. Researchers are focusing on dual (pH and temperature) responsive PMs for controlled and improved drug release at the site of action. These dual responsive systems are mainly evaluated for cancer therapy as certain malignancies can cause a slight increase in temperature and a decrease in the extracellular pH around the tumor site. This review is a compilation of updated therapeutic applications of PMs, such as PMs that are based on Pluronics®, micelleplexes and Pox-based PMs in several biomedical applications.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Educational Robotics and Tangible Devices for Promoting Computational Thinking.

Recently, efforts have been made to add programming activities to the curriculum that promote computational thinking and foster 21st-century digital skills. One of the programming modalities is the use of Tangible Programming Languages (TPL), used in activities with 4+ year old children. In this review, we analyze solutions proposed for TPL in different contexts crossing them with non-TPL solutions, like Graphical Programming Languages (GPL). We start to characterize features of language interaction, their use, and what learning activities are associated with them. Then, in a diagram, we show a relation between the complexity of the languages with factors such as target age and output device types. We provide an analysis considering the type of input (e.g., TPL versus GPL) and output devices (e.g., physical robot versus graphical simulation) and evaluate their contribution to further insights about the general trends with respect to educational robotic systems. Finally, we discuss the opportunities to extend and improve TPLs based on the different solutions identified.

Impacto de um programa de reabilitação cardíaca home-based no doente com doença cardiovascular: revisão sistemática da literatura / Impact of a home-based cardiac rehabilitation programme on patients with cardiovascular disease: a systematic review of the literature

Alguns estudos têm mostrado que a reabilitação cardíaca pode melhorar a função cardíaca de indivíduos com doenças cardiovasculares. Apesar dos benefícios comprovados da reabilitação cardíaca, verifica-se um baixo índice de adesão dos doentes cardiopatas, pelo que a telerreabilitação é uma alternativa que tem demonstrado eficácia. Os Programas de Reabilitação Cardíaca são programas a longo prazo, que englobam uma avaliação médica, prescrição de exercício, modificação de fatores de risco cardiovasculares, educação e aconselhamento, com o objetivo de proporcionar ao doente com doença cardiovascular melhor qualidade de vida, diminuindo assim as recorrências aos Serviços de Saúde por agudizações da doença. Objetivo: Realizar uma revisão sistemática da literatura para avaliar o impacto de um programa de Reabilitação Cardíaca Home-Based na redução da taxa de reinternamento, na redução dos fatores de riscos cardiovasculares modificáveis e na melhoria da qualidade de vida relacionada com a saúde em doentes com doença cardiovascular. Métodos: Foi realizada uma pesquisa nas seguintes bases de dados MEDLINE/PubMed (Medical Literature Analysis and Retrieval System Online), PubMed Central® (PMC), Cochrane Library, Physiotherapy Evidence Database (PEDro), utilizando descritores na língua portuguesa ou inglesa pesquisados separadamente e em cruzamentos, sendo considerados para esta revisão apenas artigos publicados entre 2005 e 2020. Posteriormente, foi realizada uma pesquisa manual por meio de artigos selecionados. Resultados: A estratégia de busca reuniu 205 estudos, dos quais 164 foram excluídos por não corresponderem aos critérios de inclusão, 21 por não serem estudos clínicos e dois por não apresentarem o artigo completo disponível. Foram incluídos 20 estudos clínicos para análise na íntegra, dos quais 15 foram excluídos tendo sido no final, incluídos 5 estudos. Conclusão: A reabilitação cardíaca utilizando telerreabilitação é uma alternativa viável e segura podendo ser utilizada em adição aos programas de reabilitação cardiovascular convencionais ou ainda de maneira isolada.

Several studies have shown that cardiac rehabilitation can improve cardiac function in patients with heart disease. Despite the proven benefits of cardiovascular rehabilitation, the alternative of telerehabilitation has gained importance, and many studies are being carried out to verify its efficacy. Cardiac Rehabilitation Programs are long-term programs, which include a medical evaluation, exercise prescription, modification of cardiovascular risk factors, education and counseling, with the objective of providing the patient with cardiovascular disease, a better quality of life, thus decreasing the recurrences to the Health Services due to the worsening of the disease. Aim: To conduct a systematic review of the literature to assess the efficacy of telerehabilitation in reducing the rate of readmission, in reducing modifiable cardiovascular risk factors and in improving health-related quality of life in patients with cardiovascular disease. Methods: Systematic search was performed, using the data bases EDLINE/PubMed (Medical Literature Analysis and Retrieval System Online), PubMed Central® (PMC), Cochrane Library, and Physiotherapy Evidence Database (PEDro). The descriptors used were portuguese or english language, surveyed separately and combined, considering for this review articles that were published between 2005 and 2020. Then, a manual search by use of the articles selected was conducted. Results: The search strategy collected 205 studies, of which 164 were excluded because did not match the inclusion requirements, 21 for not being clinical studies, and two Full because full texts were not available. Twenty clinical studies were included for full analysis, of which 15 were excluded. Thus, 5 studies were included. Conclusion: Cardiac rehabilitation using telerehabilitation is a feasible and safe alternative to conventional rehabilitation, and can be added to conventional cardiovascular rehabilitation programs or used in isolation/ on its own.

Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomics.

Nitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S-nitrosylation. This post-translational modification consists in the formation of a nitrosothiol group (R-SNO) in cysteine residues, which can promote formation of other oxidative modifications in those cysteine residues. S-nitrosylation can regulate many physiological processes, including neuronal plasticity and neurogenesis. In this work, we aimed to identify S-nitrosylation targets of NO that could participate in neurogenesis. In NSC, we identified a group of proteins oxidatively modified using complementary techniques of thiol redox proteomics. S-nitrosylation of some of these proteins was confirmed and validated in a seizure mouse model of hippocampal injury and in cultured hippocampal stem cells. The identified S-nitrosylated proteins are involved in the ERK/MAPK pathway and may be important targets of NO to enhance the proliferation of NSC.

Impacto de um programa de competências parentais no stress e competências de atenção plena / Impacto de un programa de competencias parentales en el estrés y en competencias de atención plena / Effects of a parenting education program on parenting skills, parenting stress, and mindfulness skills

Resumo Objetivo: Analisar o impacto da frequência do Adults and Children Together Raising Safe Kids (ACT-RSK) Programe nas competências parentais, no stress parental e nas competências de atenção plena, de um grupo de pais de crianças. Métodos: Realizou-se uma investigação-ação, utilizando um pré e pós-teste, tendo por referência a implementação do programa ACT-RSK, em 8 sessões de 90 minutos com periodicidade semanal, numa amostra de 22 pais da região Centro de Portugal. Utilizaram-se os questionários do Programa ACT-RSK, o Índice de Stress Parental, a Escala de Mindfulness Interpessoal na Parentalidade e um questionário sociodemográfico. A análise descritiva e inferencial ( Wilcoxon ) foi realizada com recurso ao Statistical Package fos Social Sciences (SPSS - IBM 24), com grau de confiança de 95%. Resultados: Os participantes melhoraram, do pré para pós-teste, nas 4 dimensões do programa: estilos parentais (M=36.32±6.61 vs. M=48.50±4.31; p<0.01); meios de comunicação (M=24.73±3.90 vs. M=30.73±2.90; p≤0.01); desenvolvimento infantil (M=55.18±11.82 vs. M=73.55±4.04; p≤0.01); e comportamento dos pais (M=34.23±7.83 vs. M=43.05±2.81; p≤0.01). Destacam-se, igualmente, melhorias consideráveis nos resultados da Escala de Mindfulness Interpessoal na Parentalidade (Z=-3.929, p=0.000) e no stress parental, que desceu do nível muito elevado (91.59) para o nível médio (74.45). Conclusão: Constata-se o impacto positivo do ACT-RSK na melhoria das variáveis estudadas.

Resumen Objetivo: Analizar el impacto de la frecuencia del Adults and Children Together Raising Safe Kids (ACT-RSK) Programe en las competencias parentales, en el estrés parental y en las competencias de atención plena de un grupo de padres de niños. Métodos: Se realizó una investigación-acción utilizando un pretest y postest en la implementación del programa ACT-RSK, en 8 sesiones de 90 minutos con frecuencia semanal, en una muestra de 22 padres de la región Centro de Portugal. Se utilizaron los cuestionarios del programa ACT-RSK, el Índice de Estrés Parental, la Escala de Mindfulness Interpersonal en la Paternidad y un cuestionario sociodemográfico. El análisis descriptivo e inferencial ( Wilcoxon ) fue realizado con el Statistical Package for Social Sciences (SPSS - IBM 24), con nivel de confianza de 95 %. Resultados: Del pretest al postest, los participantes demostraron una mejora en las cuatro dimensiones del programa: estilos parentales (M=36,32±6,61 vs. M=48,50±4,31; p<0,01); medios de comunicación (M=24,73±3,90 vs. M=30,73±2,90; p≤0,01); desarrollo infantil (M=55,18±11,82 vs. M=73,55±4,04; p≤0,01); y comportamiento de los padres (M=34,23±7,83 vs. M=43,05±2,81; p≤0,01). Además, se destacan mejoras considerables en los resultados de la Escala de Mindfulness Interpersonal en la Paternidad (Z=-3,929, p=0,000) y el en estrés parental, que se redujo de un nivel muy elevado (91,59) a un nivel medio (74,45). Conclusión: Se verifica un impacto positivo del ACT-RSK en la mejora de las variables estudiadas.

Abstract Objective: To analyze the impact of the Adults and Children Together Raising Safe Kids (ACT-RSK) Program in parenting skills, parenting stress, and mindfulness skills in a group of parents and children. Methods: This investigative intervention was based on the application of a pre-test and a post-test before and after the implementation of the ACT-RSK Program. The program consisted of eight weekly 90-minute sessions conducted with a sample of 22 parents from Central Portugal. The ACT-RSK Program questionnaires, Parenting Stress Index (PSI), Interpersonal Mindfulness in Parenting (IM-P) scale, and a socio-demographic questionnaire were used. A descriptive and inferential analysis (Wilcoxon) was conducted using the Statistical Package for Social Sciences (IBM SPSS, v. 24) with a 95% confidence interval. Results: Participants showed improvement from pre-test to post-test in all four program dimensions: Parenting Style (M=36.32±6.61 vs. M=48.50±4.31; p<0.01); Electronic Media (M=24.73±3.90 vs. M=30.73±2.90; p≤0.01); Child Development (M=55.18±11.82 vs. M=73.55±4.04; p≤0.01); and Parental Behavior (M=34.23±7.83 vs. M=43.05±2.81; p≤0.01). Likewise, significant improvement was seen in the Interpersonal Mindfulness in Parenting (IM-P) scale's results (Z=-3.929, p=0.000) and in parenting stress, which decreased from a very high (91.59) to a medium level (74.45). Conclusion: Data show the ACT-RSK had a positive effect and improved study variables.

FELASA accreditation of education and training courses in laboratory animal science according to the Directive 2010/63/EU.

THE FOUR EU FUNCTIONS AND BEYOND: FELASA accredits courses that fulfil the requirements of Functions A, B, C and D as defined by EU Directive, Article 23, as well as for designated veterinarians and specialists in laboratory animal science. MODULARITY AND MOBILITY: Cohesive courses for Functions and for very specific topics are accredited, but flexibility and mobility are possible: a researcher can start his/her training with one FELASA accredited course and complete other modules with another. A course organizer will deliver a FELASA certificate relating to the successfully completed modules. ACCREDITATION PROCESS: The process consists of two major steps: (1) a review of full course documentation provided by the applicant will lead, if successful, to FELASA accreditation. The course is posted on the FELASA website as 'FELASA accredited' and the course provider can deliver FELASA certificates upon successful completion of the course; (2) successful accreditation is followed by an on-site course audit. In the case of a negative outcome of the audit, FELASA accreditation is withdrawn, the course is deleted from the list of FELASA accredited courses and FELASA certificates cannot be issued. To ensure that quality is maintained, continuation of accreditation requires regular revalidation.

S-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model.

AIMS: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, downstream of the epidermal growth factor receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed at studying the possible neurogenic action of NO by post-translational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSCs). RESULTS: We show that NO caused S-nitrosylation (SNO) of p21Ras in Cys118, which triggered downstream activation of the ERK/MAPK pathway and proliferation of NSC. Moreover, in cells overexpressing a mutant Ras in which Cys118 was replaced by a serine-C118S-, cells were insensitive to NO, and no increase in SNO, in ERK phosphorylation, or in cell proliferation was observed. We also show that, after seizures, in the presence of NO derived from inducible nitric oxide synthase, there was an increase in p21Ras cysteine modification that was concomitant with the previously described stimulation of proliferation in the dentate gyrus. INNOVATION: Our work identifies p21Ras and its SNO as an early target of NO during signaling events that lead to NSC proliferation and neurogenesis. CONCLUSION: Our data highlight Ras SNO as an early event leading to NSC proliferation, and they may provide a target for NO-induced stimulation of neurogenesis with implications for brain repair. Antioxid. Redox Signal. 28, 15-30.

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.

Caffeine prophylactically prevents mood and memory impairments through adenosine A2A receptor (A2AR) antagonism. A2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A2AR density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A2AR agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A2AR antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A2AR controlling synaptic glutamatergic function.

Interobserver agreement on cortical tracer transit in 99mTc-MAG3 renography applied to congenital hydronephrosis.

OBJECTIVE: This study aims to evaluate interobserver agreement on visual analysis of technetium-99m mercaptoacetyltriglycine (Tc-MAG3) renal tissue transit used for the evaluation of antenatal hydronephrosis. MATERIALS AND METHODS: Thirty-eight Tc-MAG3 diuretic renograms were retrospectively collected between 1 and 31 December 2015. The 1-min reframed images were presented to four nuclear medicine consultants and to two nuclear medicine residents, one in the first year of the training program and the others in their fourth and final year. These observers were asked to classify the radiotracer cortical transit (normal/delayed) based solely on visual assessment of the images. For the interobserver agreement, modified Fleiss' kappa (κ) analysis for multiple raters was carried out. For both groups, percentages of agreement were also calculated. RESULTS: A total of 69 kidneys were evaluated. All four nuclear medicine consultants agreed on the classification of 88.4% of the kidneys. When the agreement of at least three of the four observers was considered, the percentage of agreement reached 98.6%. The two nuclear medicine residents agreed on the classification of 69.6% of the kidneys. The modified Fleiss' κ-value was 0.88 (95% confidence interval: 0.79-0.95) for the group of nuclear medicine consultants, indicating almost perfect agreement. For the residents, it was 0.39 (95% confidence interval: 0.16-0.59), suggesting fair agreement. CONCLUSION: Our results seem to indicate that there is an almost perfect agreement in the qualitative identification of delayed cortical transit among physicians with experience at observing renographic images.

Seroprevalence of anti-Toxoplasma gondii and anti-Neospora caninum antibodies in domestic mammals from two distinct regions in the semi-arid region of Northeastern Brazil.

The study was conducted to determine the seroprevalence of anti-Toxoplasma gondii and anti-Neospora caninum antibodies in goats, sheep, dogs and cats from two distinct regions in the semi-arid region of Northeastern Brazil: Serra das Confusões National Park (SCNP), a preserved area; and municipality of Petrolina, a non-preserved area. Overall, by the indirect fluorescent antibody test (IFAT), the prevalence for IgG anti-T. gondii antibodies in goats was 5.1% (19/376) and 2.4% (9/376); in sheep, it was 10.2% (34/332) and 14.2% (47/332); in dogs, it was 19.7% (25/127) and 3.9% (5/127) and, in cats, it was 25.7% (9/35) and 5.7% (5/35), for T. gondii and N. caninum, respectively. For T. gondii infection, the risk factors associated with the seroprevalence was gender (female) and study area (Petrolina) for goats and only the study area (Petrolina) for dogs; and for N. caninum infection the risk factors were the age (six months to one year) and the study area (Petrolina) for sheep. The circulation of T. gondii and N. caninum was observed in both areas, with significative risk factors demonstrated of a degraded environment.

Ectoparasite Infestations and Canine Infection by Rickettsiae and Ehrlichiae in a Semi-Arid Region of Northeastern Brazil.

This study investigated the prevalence of Rickettsia spp. and Ehrlichia canis infection in dogs and their ectoparasites from rural and urban areas of two municipalities, Petrolina and Juazeiro, within a semiarid region (Caatinga biome) of northeastern Brazil, by immunofluorescence assay (IFA) and polymerase chain reaction (PCR). Overall, 12.1% (61/504) and 23.0% (116/504) of canine plasma samples had antibodies reactive to Rickettsia spp. and E. canis. E. canis DNA was detected by PCR in 8.3% (42/504) of canine blood samples, whereas no blood sample was positive for Rickettsia spp. The infection by E. canis was determined by PCR in 4.9% (14/285) Rhipicephalus sanguineus sensu lato (s.l.) ticks and by Rickettsia felis in 1.1% (3/285) and 40.6% (74/182) ticks and fleas, respectively. Multivariate regression analyses revealed that canine seropositivity to Rickettsia spp. was associated statistically with the variables "to reside in Petrolina" and "presence of ectoparasites." Our results indicate that canine infection by E. canis might be endemic in the Caatinga biome as it is in other Brazilian biomes. Although no previous serosurvey for Rickettsia spp. has been conducted on dogs from the Caatinga biome, our values are much lower than the ones reported for rural dogs from other Brazilian biomes. These differences are likely related to the semiarid climate of the aatinga biome, which minimizes the exposure of rural dogs to Amblyomma spp. ticks, the most common vectors of Rickettsia spp. in Brazil. Considering that dogs are excellent sentinels for human exposure to Rickettsia spp., we can infer that the risks of human acquiring tick-borne rickettsiosis in the Caatinga region of the present study are low. The rickettsial infection rates in fleas and ticks were not related to canine seropositivity; i.e., areas with higher Rickettsia infection rates in fleas had the lowest canine seroreactivity to Rickettsia spp.