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Abstract Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity.

Abstract Being immersed in a natural context has a beneficial and pervasive impact on well-being. Virtual Reality (VR) is a technology that can help expose people to naturalistic scenarios virtually, overcoming obstacles that prevent them from visiting real natural environments. VR could also increase engagement and relaxation in older adults with and without cognitive impairment. The main aim of this study is to investigate the feasibility of a customized naturalistic VR scenario by assessing motion-sickness effects, engagement, pleasantness, and emotions felt. Twenty-three individuals with a diagnosis of cognitive impairment living in a long-term care home participated in our study. At the end of the entire VR experimental procedure with older adults, five health staff operators took part in a dedicated assessment phase focused on evaluating the VR procedure's usability from their individual perspectives. The tools administered were based on self-reported and observational tools used to obtain information from users and health care staff professionals. Feasibility and acceptance proved to be satisfactory, considering that the VR experience was well-tolerated and no adverse side effects were reported. One of the major advantages emerged was the opportunity to deploy customized environments that users are not able to experience in a real context. Trial Registration: National Institute of Health (NIH) U.S. National Library of Medicine, ClinicalTrials.gov NCT05863065 (17/05/2023).

Abstract Humanized mice have been used to study human immunodeficiency virus type 1 (HIV-1) transmission, pathogenesis, and treatment. The ability of pediatric thymus tissue implanted either in the leg (Leg PedThy) or under the renal capsule (Renal PedThy) with allogeneic CD34+ hematopoietic cells (HSCs) in NSG mice was evaluated for reconstitution of human immune cells and for rectal transmission of HIV-1. These mice were compared to traditional BLT mice implanted with fetal liver and thymus under the renal capsule and mice injected only with HSCs. Renal PedThy mice had similar immune reconstitution in the blood, spleen and intestine as BLT mice, while Leg PedThy mice had transient detection of immune cells, particularly CD4+ T cells and macrophages, the target cells for HIV-1 infection. Rectal transmission and replication of HIV-1 was efficient in BLT mice but lower and more variable in Renal PedThy mice. HIV-1 was poorly transmitted in HSC mice and not transmitted in Leg PedThy mice, which correlated with the frequencies of target cells in the spleen and intestine. Humanization of NSG mice with pediatric thymus was successful when implanted under the kidney capsule, but led to less efficient HIV-1 rectal transmission and replication compared to BLT mice.

Abstract Background The liver is a common site for metastatic disease for a variety of cancers, including colorectal cancer. Both primary and secondary liver tumors are supplied through the hepatic artery while the healthy liver is supplied by the portal vein. Transarterial radioembolization (TARE) using yttrium-90 glass or resin microspheres have shown promising results with reduced side-effects but have similar survival benefits as chemoembolization in patients with hepatocellular carcinoma (HCC). This highlights the need for new novel agents against HCC. Targeted alpha therapy (TAT) is highly potent treatment due to the short range (sparing adjacent normal tissue), and densely ionizing track (high linear energy transfer) of the emitted α-particles. The incorporation of α-particle-emitting radioisotopes into treatment of HCC has been extremely limited, with our recent publication pioneering the field of α-particle-emitting TARE (αTARE). This study focuses on an in-depth evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as an effective therapeutic agent against HCC regarding pharmacokinetics, dosimetry, stability, and therapeutic efficacy. Results [225Ac]Ac-DOTA-TDA was shown to be a highly stable with bench-top stability at ≥ 95% radiochemical purity (RCP) over a 3-day period and serum stability was ≥ 90% RCP over 5-days. The pharmacokinetic data showed retention in the tumor of [225Ac]Ac-DOTA-TDA-Lipiodol® and clearance through the normal organs. In addition, the tumor and liver acted as suppliers of the free daughters, which accumulated in the kidneys supplied via the blood. The dose limiting organ was the liver, and the estimated maximum tolerable activity based on the rodents whole-body weight: 728–3641 Bq/g (male rat), 396–1982 Bq/g (male mouse), and 453–2263 Bq/g (female mouse), depending on an RBE-value (range 1–5). Furthermore, [225Ac]Ac-DOTA-TDA-Lipiodol® showed significant improvement in survival for both the male and female mice (median survival 47-days) compared with controls (26-days untreated, and 33–35-days Lipiodol® alone). Conclusions This study shows that [225Ac]Ac-DOTA-TDA-Lipiodol® is a stable compound allowing for centralized manufacturing and distribution world-wide. Furthermore, the result of this study support the continue development of evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as a potential treatment option for treating hepatic tumors.

Objetivo: avaliar a condição miofuncional orofacial de indivíduos com disfunção temporomandibular, caracterizar o padrão de mastigação e investigar a relação entre a condição miofuncional orofacial e o desempenho nas funções de mastigação e deglutição. Materiais e métodos: foram analisados prontuários de participantes de um projeto de extensão interdisciplinar de odontologia e fonoaudiologia. A idade mínima para compor a amostra foi 18 anos. Os participantes haviam realizado exame odontológico e avaliação fonoaudiológica, com o protocolo de Avaliação Miofuncional Orofacial com Escores. Os resultados foram apresentados por distribuição absoluta, relativa e medidas de tendência central. Foram aplicados o teste t-student para amostras independentes e correlação de Pearson para avaliar associação. O nível de significância adotado foi 5%. As análises foram realizadas no IBM SPSS Statistics 21. Resultados: Dezessete prontuários integraram a amostra. A média de idade dos participantes foi 41,2 anos (±12,2), 76,5% eram do sexo feminino. A média do escore total (AMIOFE) indicou condição miofuncional normal (92,5±5,14), porém da mastigação (7,94±1,60) e deglutição (13,1±1,17) revelam prejuízos funcionais. Não houve diferença significativa entre homens e mulheres no escore total (p=0,687), tampouco nas diferentes categorias avaliadas. Discussão: Os escores totais encontrados neste estudo, na mastigação e deglutição, estão de acordo com outras pesquisas realizadas e revelam alteração na função. Conclusão: as alterações funcionais orofaciais encontradas nos indivíduos com disfunção temporomandibular crônica deste estudo estão relacionadas com a condição miofuncional orofacial de uma maneira geral, e devem ser consideradas na elaboração de planos de tratamento, com o objetivo de proporcionar maior estabilidade aos resultados.

4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution leaving other phosphorylation sites intact. S82A mice were fertile and exhibited no gross developmental or behavioral abnormalities, but the homozygotes developed diffuse and severe polycystic liver and kidney disease with aging, and lymphoid malignancies after irradiation. Sublethal irradiation caused immature T-cell lymphoma only in S82A mice while S82A homozygous mice have normal T-cell hematopoiesis before irradiation. Whole genome sequencing identified PTEN mutations in S82A lymphoma and impaired PTEN expression was verified in S82A lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to polycystic proliferative disease and lymphoma under certain stressful circumstances, such as aging and irradiation.

Background: D-dimer levels are significantly higher in COVID-19 patients with Pulmonary Thromboembolism (PTE) as compared to those without PTE, but its clinical utility is still uncertain. Purpose: To determine the D-dimer performance for ruling out PTE in patients with COVID-19. We also assessed clinical and laboratory factors associated with the presence of PTE on CT Pulmonary Angiogram (CTPA). Methods: Retrospective study involving all patients who presented at a tertiary care hospital from March 2020 to May 2021 with severe acute respiratory syndrome from COVID-19, who underwent CTPA and had D-dimer collected within 48 hours from CTPA. The D-dimer ability to classify patients with or without PTE according to CTPA was evaluated. Results: A total of 697 patients [382 (54.8%) men; mean (SD) age, 59 (20.5) years] were included, of which 71.5% required intensive care admission, 32.4% had PTE, and 35.6% died during hospitalization. PTE was independently associated with mortality [42.5% vs. 32.3%; p = 0.038]. D-dimer levels were higher in patients with PTE [9.1 (3.9; 20) vs. 2.3 (1.2; 5.1); p < 0.001]. Using the D-dimer cutoff of 0.5 μg/mL or above, sensitivity was 98.2% and specificity 5.7%. The 0.3 μg/mL threshold was associated with 100% of sensitivity for the presence of PTE, with which 99.1% of patients had increased values. ROC curve AUC was 0.77, demonstrating moderate discriminative power of D-dimers to detect PTE. Conclusions: D-dimer levels are higher among COVID-19 hospitalized patients with PTE as compared to those without PTE and have moderate discriminative power to detect PTE, but its use to exclude PTE in this population may have limited clinical utility.

Tratamos neste ensaio teórico do saber linguístico do falante para além de sua competência linguística, focando especificamente em situações em que os falantes refletem sobre seus usos linguísticos. Baseando-se na nomenclatura empregada por Franchi (2006) e Geraldi (2013), defendemos que é possível encontrar na internet situações em que o falante emprega uma reflexão sobre sua língua de maneira particular, exercendo atividades epilinguísticas, e também situações em que o falante traça uma reflexão mais generalizada sobre questões linguísticas, através de atividades metalinguísticas, mesmo não empregando termos técnicos da área. Essas situações circulam sob diversos gêneros e inclusive alcançam repercussão através de virais, como memes, tuítes e tirinhas, e ilustramos neste trabalho casos assim através de comentários coletados no Twitter. Defendemos que essa sabedoria gramatical deve ser valorizada, tanto em sala de aula quanto no espaço acadêmico. Ilustramos a pertinência desse tipo de texto em práticas de divulgação científica, através de post produzido por uma das autoras. Discutimos também a possibilidade de incluir esses textos em aulas de língua portuguesa, especialmente considerando a etapa de descoberta proposta na metodologia de Lobato (2015). Da mesma forma, afirmamos que a manipulação de propriedades linguísticas por pessoas não especialistas pode ser acolhida em propostas de ciência cidadã, abrindo portas para um fazer científico mais participativo.

The present study investigates shared phonological information and selectivity during lexical access in Brazilian Portuguese-English unbalanced bilinguals, learners of Korean as an L3. Participants took part in a word naming task which used L2 primes with targets from the L3 at stimulus onset asynchronies (SOA) of 140ms and 250ms. The results show a significant facilitation effect in word naming when an English prime was presented in comparison with control primes. Additionally, a significant facilitation effect was also seen in trials in which the primes were presented at a 250ms SOA in relation to a 140ms SOA. Taken together, the results indicate that participants’ spelling-sound knowledge of L2 English was activated during the reading aloud of words in L3 Korean, which indicates nonselectivity in lexical access and a shared mental lexicon across languages.

Introduction: Ectopic adrenal tissue in the kidney, including “Ectopic adrenal tissue” and “Adrenal-renal fusion”, is a rare event with a specific behavior which may be difficult to distinguish clinically from renal neoplasms. We performed a systematic review on ectopic adrenal tissue variants reported in the literature underlining its clinical aspects. Methods: Manuscripts which presented a case report or case series of ectopic adrenal tissue in the kidney were included even if published in original articles, reviews, or letters to the editor. A specific search on SCOPUS®, PubMed®, and Web of Science® database was performed. Only English language papers published in a period ranging between August 1991 and April 2020 were considered. Additionally, a case we had at our institution is described, and its characteristics are included. Data on clinical presentation, type of adrenal anomaly, location, anatomopathological and immune-histotype characteristics were collected. Results: We identified 888 manuscripts. Among these 29 were included in this systematic review. Overall, 39 patients with renal adrenal fusion or adrenal ectopia were considered. In most cases, the diagnosis was made incidentally, or following investigation for flank pain, abdominal pain, or endocrinological disorders. CT scan frequently identified a solid vascularized lesion that was difficult to distinguish from renal neoplasm. Adrenal fusion was mostly located at the level of the upper pole. Adrenal rest was found in the renal parenchyma, renal hilum, or retroperitoneum in close proximity to the renal peduncle. Often these ectopic adrenal tissue lesions follow a benign behavior and can be classified as functioning or non-functioning adenomas. Rarely, they may experience neoplastic degeneration. The most frequently positive markers were inhibin, vimentin, melan-A, synaptophysin and anti-p450 scc. Conclusions: Ectopic adrenal tissue in the kidney is a rare event with specific clinical characteristics that need to be identified in order to arrive at a correct diagnosis and carry out appropriate treatment management.

Objetivo: analisar a percepção dos técnicos de enfermagem sobre o cuidado em terapia nutricional enteral, durante um cenário de simulação clínica. Método: estudo qualitativo, com base em um cenário de simulação clínica, realizado com 64 técnicos de enfermagem, em um hospital universitário do Sul do Brasil, em agosto de 2017. As falas foram audiogravadas, transcritas e, posteriormente, submetidas a análise de conteúdo. Resultados: foram evidenciadas quatro categorias sobre o cuidado em terapia nutricional enteral nas etapas de: administração da TNE; manutenção da sonda nasoenteral; registros de enfermagem e orientações ao paciente em uso de TNE. Conclusão: refletir sobre o cuidado prestado, por meio de um cenário de simulação clínica, pode colaborar com melhorias acerca do processo de trabalho da equipe de enfermagem e com o fortalecimento e segurança dos cuidados prestados.

ABSTRACT Objective To develop and validate the content of workflows for trial participants care in a clinical research center during the Covid-19 pandemic. Method development study by consensus of experts carried out from March to July 2020 in southern Brazil. The flowcharts were developed following literature and validated by specialists considering comprehensiveness, clarity and pertinence, obtaining a 100% agreement index on each item of the developed instruments. The study was approved by the Ethics Committee of the institution. Results two flowcharts of care were elaborated and validated: “Flow diagram to conduct protocols with research participant " and "Flow diagram in protocols with research participant with suspected or confirmed COVID-19 infection"; which describes activities to ensure continuity of care. Final considerations a routine workflow can promote the continuity and safety of clinical research protocols. It is expected that the adopted flowcharts in this study can guide other institutions with a similar research profile.

Este trabalho investiga as diferentes narrativas suscitadas pela implantação de um calçadão no centro de Santa Maria, interior do Rio Grande do Sul em 1979. Analisaram-se o discurso e as ações de um conjunto de atores sociais, a partir da perspectiva da História Cultural, tendo como fontes uma entrevista e reportagens de jornal. Os moradores da chamada Primeira Quadra foram os que se mostraram mais contrários à sua transformação em calçadão. Já a Prefeitura, o arquiteto responsável pelo projeto, os comerciantes e os usuários do espaço apresentaram discursos alinhados em torno de um objetivo comum: construir a imagem de um centro mais humano e moderno, do mesmo modo como cidades maiores estavam fazendo.

Introduction: The aim of the study is to evaluate the effectiveness of a Multi-disciplinary team (MDT) and multi-disciplinary approach in the treatment of Chronic Pelvic Pain (CPP). Methods: The data of all consecutive patients referred for a CPP from 11/2016 to 2/2019 has been prospectively collected. The sample was divided in two groups: Group A, made by patients managed after the institution of our MDT, and Group B, made of patients managed before this date. The MDT is composed by three urogynecologists, a psychologist and a physiotherapist. All Group A patients underwent a weekly bladder instillation with dimethyl sulfoxide (DMSO), kinesiotherapy for trigger points and Percutaneous Tibial Nerve Stimulation for 10 consecutive weeks. Patients were asked to perform a self-treatment following the Stanford Protocol and to adhere to a specific diet. All Group B patients were managed only with DMSO instillations and a strict diet. Results: The Group A was made of 41 females and 6 males while the Group B was made of 38 females and 5 males. The Group A patients showed a statistically significant improvement in the Pelvic Pain Urgency Frequency, in the frequency times reported at the 6 months voiding diary, and a better Patient Global Impression of Improvement. Conclusions: Our data support the efficacy of the MDT in the management of CPP. The multimodal approach might represent an effective and reproducible non-invasive option to manage successfully CPP.

Objetivo: compreender como a equipe de enfermagem percebe a simulação clínica como metodologia de educação no cuidado ao paciente hospitalizado em uso de sonda nasoenteral. Método: trata-se de um estudo exploratório, descritivo, de abordagem qualitativa, realizado com 64 técnicos de enfermagem em um hospital de Porto Alegre, no Sul do Brasil, em agosto e setembro de 2017. Realizou-se uma intervenção de educação por meio de simulação clínica, as quais foram gravadas e transcritas. Utilizou-se a análise de conteúdo para tratamento dos dados. Resultados: foram estabelecidas duas categorias: as potencialidades da simulação clínica como metodologia de educação e os desafios da simulação clínica para a prática da educação. Conclusão: os profissionais da enfermagem perceberam as potencialidades da atividade de simulação e se mostraram colaborativos e preocupados em revisar as práticas de cuidados em terapia nutricional enteral. A simulação clínica é uma metodologia promissora a ser utilizada na educação permanente em serviço.

Introduction: Although the literature supports the importance of physical activity in the oncological context, in Italy a large number of patients are not sufficiently active. Methods: The present study aimed to explore factors influencing an active lifestyle in cancer patients during oncological treatments. Semi-structured focus groups, including 18 patients with different cancer types, were conducted at the Oncology Unit in the University Hospital Trust of Verona (Italy). The interviews were audio-recorded, transcribed verbatim, and analyzed with content analysis. Results: According to the Health Belief Model, transcripts were categorized into the following themes: benefits, barriers, and cues to action. Patients reported a series of physical, physiological, and psychological benefits deriving from an active lifestyle. The main barriers hampering the physical activity participation were represented by treatment-related side effects, advanced disease, and some medical procedures, for example, ileostomy. Several strategies that can trigger patients to exercise were identified. Medical advice, social support from family and friends, features such as enjoyment, setting goals, and owning an animal can motivate patients to perform physical activity. At the same time, an individualized program based on patients’ characteristics, an available physical activity specialist to consult, more detailed information regarding physical activity in the oncological setting, and having accessible structures were found important facilitators to implementing active behavior. Conclusions: Overall, patients have a positive view regarding physical activity, and a variety of obstacles and cues to action were recognized. Considering this information may help to improve adherence to a physical activity program over time, consequently increasing the expected benefits.

Background and Objectives: To evaluate the oncological impact of squamous cell carcinoma (SCC) variant in patients submitted to intravesical therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: Between January 2015 and January 2020, patients with conventional urothelial NMIBC (TCC) or urothelial NMIBC with SCC variant (TCC + SCC) and submitted to adjuvant intravesical therapies were collected. Kaplan–Meier analyses targeted disease recurrence and progression. Uni- and multivariable Cox regression analyses were used to test the role of SCC on disease recurrence and/or progression. Results: A total of 32 patients out of 353 had SCC at diagnosis. Recurrence was observed in 42% of TCC and 44% of TCC + SCC patients (p = 0.88), while progression was observed in 12% of both TCC and TCC + SCC patients (p = 0.78). At multivariable Cox regression analyses, the presence of SCC variant was not associated with higher rates of neither recurrence (p = 0.663) nor progression (p = 0.582). Conclusions: We presented data from the largest series on patients with TCC and concomitant SCC histological variant managed with intravesical therapy (BCG or MMC). No significant differences were found in term of recurrence and progression between TCC and TCC + SCC. Despite the limited sample size, this study paves the way for a possible implementation of the use of intravesical BCG and MMC in NMIBC with histological variants.

ABSTRACT Objectives: To assess the results of a brief antibullying intervention for adolescents in public schools. Method: This was a controlled experimental study whose subjects were 1,043 students in 5th through 9th grades from public schools in Porto Alegre/State of Rio Grande do Sul, conducted between April and November 2015. Adolescents and school teachers randomly assigned to the intervention group participated in two meetings focused on educative aspects of bullying. Outcome was assessed using the Bullying Questionnaire - victim and perpetrator version. Generalized Estimating Equations was used to evaluate the effect of the intervention. Results: Average age of subjects was 12.5 (SD=1.62) years. A total of 613 (58.7%) adolescents participated in interventions. They were compared to 430 (41.3%) participants in the control group. The study did not observe any significant difference in bullying scores after the intervention. Conclusions: This study indicates the usefulness of clarifying precisely what bullying is in schools as part of an initial approach to an educative strategy on this topic.

ABSTRACT Objective To analyze the latency and the amplitude values of Mismatch Negativity and P300 cognitive potential in children with stuttering, with no auditory complaints, with auditory thresholds within the normality range, comparing them to the findings of a Control Group. Methods A cross-sectional study involving 50 children of both sexes, 15 with stuttering and 35 without stuttering, aged 6 to 11 years, with no diagnosis of ear pathology or other diseases. All children were submitted to peripheral audiological evaluation (meatoscopy, pure tone testing, speech audiometry, and acoustic immittance measures) and a central audiological evaluation (investigation of the Mismatch Negativity and P300 cognitive potential). For the evaluation of fluency, all children with stuttering had a specific history taken and were video recorded in a spontaneous speech. Afterwards, the transcription was done, followed by speech analysis to classify children according the severity of stuttering. Results There was a significant difference in the latencies of Mismatch Negativity and P300 cognitive potential, as well as in the amplitude of Mismatch Negativity. Conclusion There was a significant delay in the latencies of Mismatch Negativity and P300 cognitive potential, as well as increase in the amplitude of the Mismatch Negativity in children with stuttering when compared to children in the Control Group. Changes in the morphology of the waves were found in the Stuttering Group.

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/∆ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/∆ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/∆ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/∆ mice never exceeded that observed in old WT mice. Surprisingly, levels of reactive oxygen species (ROS) were increased in tissues of Ercc1-/∆ mice to an extent identical to naturally-aged WT mice. Increased enzymatic production of ROS and decreased antioxidants contributed to the elevation in oxidative stress in both Ercc1-/∆ and aged WT mice. Chronic treatment of Ercc1-/∆ mice with the mitochondrial-targeted radical scavenger XJB-5–131 attenuated oxidative DNA damage, senescence and age-related pathology. Our findings indicate that nuclear genotoxic stress arises, at least in part, due to mitochondrial-derived ROS, and this spontaneous DNA damage is sufficient to drive increased levels of ROS, cellular senescence, and the consequent age-related physiological decline. Keywords: Reactive oxygen species, Free radicals, Genotoxic stress, Oxidative lesions, Endogenous DNA damage, Cellular senescence, Aging

The tumor suppressor genes EAF2 and p53 are frequently dysregulated in prostate cancers. Recently, we reported that concurrent p53 nuclear staining and EAF2 downregulation were associated with high Gleason score. Combined loss of EAF2 and p53 in a murine model induced prostate tumors, and concurrent knockdown of EAF2 and p53 in prostate cancer cells enhanced proliferation and migration, further suggesting that EAF2 and p53 could functionally interact in the suppression of prostate tumorigenesis. Here, RNA-seq analyses identified differentially regulated genes in response to concurrent knockdown of p53 and EAF2. Several of these genes were associated with the STAT3 signaling pathway, and this was verified by significantly increased p-STAT3 immunostaining in the Eaf2−/−p53−/− mouse prostate. STAT3 knockdown abrogated the stimulation of C4-2 cell proliferation by concurrent knockdown of EAF2 and p53. Furthermore, immunostaining of p-STAT3 was increased in human prostate cancer specimens with EAF2 downregulation and/or p53 nuclear staining. Our findings suggest that simultaneous inactivation of EAF2 and p53 can act to activate STAT3 and drive prostate tumorigenesis.

Genitourinary tuberculosis (GUTB) represents a disease often underestimated by urological specialists, particularly in settings such as the European one, where the pathology is less frequent. Similar to other uncommon diseases at these latitudes, GUTB is a neglected clinical problem. In this light, the aim of this review is to give a comprehensive overview of GUTB in order to provide a useful tool for urologists who seldomly manage this disease. A non-systematic review of genitourinary tuberculosis was performed on relevant articles published from January 1990 to July 2021 using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. GUTB represents up to a quarter of extrapulmonary tuberculosis (EPTB) cases. Diagnostic, therapeutic and surgical work-up have been deeply reviewed and summarized. The mass migration of refugees to Europe as well as the ease of international travel is gradually leading to an upsurge in urological diseases such as GUTB, which were previously only rarely encountered in some European countries. The poor TB knowledge of European urologists should be improved through medical education courses, webinars or telematic means.

PurposeTo describe the ophthalmic and genetic findings in a family with X-linked retinitis pigmentosa (RP) and Coats'-like exudative vasculopathy.DesignObservational case series.MethodsFamily members underwent comprehensive ophthalmologic examination. Leukocyte genomic DNA samples were obtained and screened for RPGR (RP3) mutations by direct polymerase chain reaction sequencing.ResultsThe proband had RP with bilateral Coats'-like vasculopathy and was treated with fluorescein-potentiated argon laser therapy. The findings in two other affected male patients and three obligate carrier female patients were within the clinical spectrum of a typical X-linked-recessive RP. A novel nonsense RPGR exon ORF15 mutation (912G>T) was found to segregate with RP in this family.ConclusionsThis report expands the clinical heterogeneity spectrum caused by RPGR mutations and our knowledge concerning the molecular pathologic condition that pertains to Coats'-like RP. Consistent with the literature, Coats' response was not observed in all family members who were affected by RP, which suggests the involvement of other genetic and/or environmental factors.

PurposeTo evaluate the donor retina of a patient with X-linked cone-rod dystrophy caused by an RPGR exon ORF15 mutation.DesignHistopathologic study of the retina.MethodsThe eye of a 69-year-old man was fixed at 1.6 hours postmortem and processed for histopathology and immunocytochemistry.ResultsGrossly, the macula was atrophic with a bull's-eye appearance. The remaining retina showed postmortem edema but no intraretinal pigment. Microscopically, the macular retinal pigment epithelium was absent focally and had pigmentary changes elsewhere. Cones and rods were absent from the perifovea and reduced with shortened outer segments elsewhere in the macula. In the remainder of the retina, cones but not rods were reduced and all photoreceptor outer segments were shortened.ConclusionsThe abnormalities in both cone and rod photoreceptors confirm the importance of RPGR in both cell types but leaves unresolved how various exon ORF15 mutations lead to different clinical phenotypes.

PurposeA patient with retinitis pigmentosa demonstrated a novel RPGR mutation (213G>A, last base of exon 2) predicted to cause a missense change (G52R) in the final protein. This study was performed to determine whether this mutation altered the effectiveness of the adjacent splice site.DesignObservational case report.MethodsTotal RNA was extracted from leukocytes of the proband and his carrier mother. Reverse transcription-polymerase chain reaction (RT-PCR) was performed by using the primers flanking exon 2 of RPGR transcript, followed by gel purification and direct sequencing.ResultsSequencing revealed skipping of exon 2 in the mutated transcript, leading to in-frame deletion of 42 amino acids affecting the critical RCC1-like domain.ConclusionsThe last base of exons is conserved as "G" in 80% of splicing consensus sequences, yet when changed, can completely disrupt constitutive splicing as in this patient. Our data confirm that the evaluation of the effects of some DNA sequence alterations at the RNA level might have important implications for appropriate genotype-phenotype correlations.

PurposeTo describe a patient with retinitis punctata albescens (RPA) associated with compound heterozygosity for two novel mutations in the RLBP1 encoding cellular retinaldehyde-binding protein (CRALBP).DesignObservational case report.MethodsThe proband underwent a complete ophthalmic examination and leukocyte genomic DNA samples were obtained from him and his parents. The RLBP1 exons were analyzed by direct sequencing of PCR-amplified fragments.ResultsThe patient had a clinical phenotype suggestive of slowly progressive RPA, characterized by numerous yellow-white dots in the fundus. The RLBP1 sequence analysis revealed a novel compound heterozygotic mutation of Gly145Asp and Ile200Thr transmitted from the mother and father, respectively. Analysis of 100 control chromosomes showed no individuals with these sequence alterations.ConclusionsOnly eight RLBP1 mutations have been reported to date, and here we describe two novel mutations. These additional mutations will aid ongoing functional studies and add to our understanding of the molecular pathology pertaining to RLBP1-associated retinopathies.

X-linked cone-rod dystrophy (COD1) is a retinal disease that primarily affects the cone photoreceptors; the disease was originally mapped to a limited region of Xp11.4. We evaluated the three families from our original study with new markers and clinically reassessed all key recombinants; we determined that the critical intervals in families 2 and 3 overlapped the RP3 locus and that a status change (from affected to probably unaffected) of a key recombinant individual in family 1 also reassigned the disease locus to include RP3 as well. Mutation analysis of the entire RPGR coding region identified two different 2-nucleotide (nt) deletions in ORF15, in family 2 (delAG) and in families 1 and 3 (delGG), both of which result in a frameshift leading to altered amino acid structure and early termination. In addition, an independent individual with X-linked cone-rod dystrophy demonstrated a 1-nt insertion (insA) in ORF15. The presence of three distinct mutations associated with the same disease phenotype provides strong evidence that mutations in RPGR exon ORF15 are responsible for COD1. Genetic heterogeneity was observed in three other families, including the identification of an in-frame 12-nt deletion polymorphism in ORF15 that did not segregate with the disease in one of these families.

Este ensaio inserido no debate em torno do tema “Artista Professor – ser e estar”, reúne diversas reflexões pessoais sobre o tema, considerando também a experiência deste pesquisador como ponto de partida. No cerne desta questão, a reflexão a ser desenvolvida deverá seguir o ser e estar deste artista/professor, indagando o que significa ser um e outro, ou apenas ser em tempo integral, sou ou estou artista/professor?

The mouse hypopigmentation mutant pearl is an established model for Hermansky-Pudlak syndrome (HPS), a genetically heterogenous disease with misregulation of the biogenesis/function of melanosomes, lysosomes, and platelet dense granules. The pearl (Ap3b1) gene encodes the beta3A subunit of the AP-3 adaptor complex, which regulates vesicular trafficking. The genomic structure of the normal Ap3b1 gene includes 25 introns and a putative promoter sequence. The original pearl (pe) mutation, which has an unusually high reversion rate on certain strain backgrounds, has been postulated to be caused by insertion of a transposable element. Indeed, the mutation contains a 215-bp partial mouse transposon at the junction point of a large tandem genomic duplication of 6 exons and associated introns. At the cDNA level, three pearl mutations (pearl, pearl-8J, and pearl-9J) are caused by deletions or duplications of a complete exon(s).

The structure of a sample of rural houses built by Italian immigrants in Southern Brazil from the last quarter of the 19th century onwards and a sample of Italian rural houses were analyzed using the space syntax theory and techniques. The samples were analyzed to identify key differences in the house genotypes. The main goal of the article is to compare the results regarding the Brazilian sample of houses with the Italian sample of rural houses from the regions of Veneto and Trentino Alto‑Adige, where most of the families that had moved to Southern Brazil came from. Therefore, it will be possible to evaluate whether or not, and to which extent, the Italian immigrants reproduced in Brazil the Italian house structures they used to live in and, more importantly, the relationship between the spatial structure of the houses built in Brazil and the patriarchal social structure that governed the entire society at that time. We inferred so far that the main genotype found in the Italian sample corresponds to the genotype produced in Brazil, a time when the houses were organized around the daily life of the families and suited the prevailing patriarchal social structure. In the Brazilian case, liminal events and a more flexible house plan are able to introduce differences in the way the same house can function, depending on how strangers are admitted into the houses on liminal occasions and in the daily life of the families. In Italy, this kind of flexibility is not found. There are two main hypotheses regarding this aspect: the first one is that the immigrants tend to reproduce the structure of the houses as experienced in Italy but, at the same time, they tend to introduce in Brazil a new typology of houses based on the flexibility of the house plan that is relatively autonomous from their spatial experience in Italy. KEYWORDS: Domestic space. Rural houses. Italian immigration in Brazil.

RESUMO Objetivo Realizar a adaptação transcultural para o português brasileiro do instrumento Inventory of Callous-Unemotional Traits (ICU) para avaliação de traços de insensibilidade e afetividade restrita de adolescentes. Método Estudo metodológico que envolveu as etapas de tradução, retradução, avaliação por comitê de especialistas e de clareza da versão pré-final do ICU, avaliado por 40 adolescentes, entre 10 e 17 anos, de ambos os sexos, de uma escola pública. Resultados A versão pré-final do ICU foi aprovada pelo comitê de especialistas e pelo autor do instrumento. A avaliação da clareza revelou uma boa compreensão dos itens. Os 10 itens com menor clareza foram modificados conforme as sugestões. Conclusão A versão final do ICU para o português brasileiro mostrou ser similar ao instrumento original no que se refere à equivalência semântica, operacional e conceitual. Recomenda-se a realização de estudos que evidenciem a validade psicométrica do ICU adaptado para o português brasileiro.

Objective To conduct a systematic review about the long-term response to cognitive-behavioral therapy (CBT) for anxiety disorders (ADs) in children and adolescents. Methods The PubMed and ISI Web of Science databases were consulted. Search in the databases was performed in November 2012 and included cohort studies after CBT for ADs in children and adolescents with a follow-up period over 12 months. Results A total of 10 papers met the inclusion criteria. The follow-up period ranged from 12 months to 13 years and the results generally showed maintenance of the short-term benefits with CBT. However, the studies presented limitations, especially regarding methods, such as lack of a control group and losses to follow-up. Conclusion The long-term benefits of CBT were identified, however it would be interesting to conduct other studies with more frequent assessment periods, in order to minimize losses to follow-up, in addition to evaluating children and adolescents in the various stages of their development.