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Chagas disease (CD) is one of the main neglected tropical diseases, diagnosed mainly by serological tests performed in centralized laboratories, which severely limits the clinical management of the disease in communities with scarce resources. Herein, an electrochemical impedance biosensor for the detection of CD was developed for the first time using a cruzipain-based sensor surface. The protein, highly immunogenic and isolated from Trypanosoma cruzi, was immobilized over the surface of gold disc electrodes modified with 11-mercaptoundecanoic (MUA) and 6-mercapto-1-hexanol (MCH) self-assembled monolayers (SAMs). Reproducible sensor surfaces, yielding 38 ± 3% coverage as measured by Surface Plasmon Resonance, were obtained by amide coupling of 120 μg/mL cruzipain onto 1/10 MUA/MCH SAMs for 30 min. Under optimized operational conditions, the impedimetric immunosensor recognized specific interactions for anti-T. cruzi antibodies in 1/800 diluted human serum patient samples. The charge transfer resistance of the biosensors increases by ∼18% in the presence of the positive samples, whereas the negative samples give rise to a negligible increase of around 6%. An excellent selectivity to clinical samples from patients infected with T. cruzi was obtained. The clear signal difference obtained for positive and negative clinical samples highlights the applicability of the sensors for the point-of-care diagnosis of CD.

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) – a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities’ wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.

Abstract Antibiotic resistance (AR) poses a significant challenging issue in public health worldwide. This phenomenon led to the emergence of antibiotic-resistant bacterial strains, making the treatment of respiratory infections increasingly difficult. Educational interventions targeting healthcare professionals are important to improve prescription practices and promote responsible antibiotic use. Digital tools, including clinical decision support systems and mobile applications, have proven to effectively enhance educational interventions and clinical decision-making. The eHealthResp project is one such initiative that includes an online course and a mobile app designed to improve antibiotic use for upper respiratory tract infections (URTIs). The online course provides clinical information and case studies, whereas the mobile app acts as a clinical decision support system for URTIs diagnosis. The purpose of this study is to analyse the utilization patterns of eHealthResp digital tools among primary care physicians and community pharmacists. Results showed that both physicians and pharmacists (n = 35) had favorable progress and high grades when completing the online course assessment. The mobile app data indicated a diverse range of searched cases with different respiratory symptoms, with the most common being acute nasal discharge and pain when swallowing. Most observations presented mild symptoms for less than seven days, suggesting the occurrence of acute self-limited infections. Despite limitations, digital tools show promise in enhancing patient care outcomes for managing URTIs. Future efforts should focus on expanding participation among health professionals and enhancing educational interventions to promote responsible antibiotic use.

Introduction: Acute hydrops is a rare initial manifestation of Primary Congenital Glaucoma (PCG). It can result in significant corneal opacity, posing an additional risk for amblyopia development in PCG patients. We report a case of a newborn with PCG presenting with acute corneal hydrops and significant corneal scarring, discussing the management and challenges of amblyopia prevention. Case Presentation: A 3-day-old female newborn was referred to our department due to bilateral corneal clouding. Anterior segment examination revealed bilateral corneal edema, with severe corneal prolapse in the right eye consistent with acute hydrops. The anterior chamber structures of the right eye were indiscernible due to significant corneal edema. The left eye presented a deep, quiet anterior chamber with no dysgenesis of anterior segment structures. Intraocular pressure (IOP) measurements were >40 mmHg in both eyes. Corneal diameters were 10 mm OD and 12 mm OS. Fundoscopic posterior segment assessment was not possible due to unclear media. B-scan ultrasonography revealed no significant changes. The patient underwent urgent bilateral trabeculotomy. Postoperatively, intense mechanical stretching induced by severely increased IOP was visible, with the right cornea exhibiting a central opacity managed with topical corticosteroids and showing improvement. Right corneal opacity spared the superior cornea, and atropine drops combined with left eye occlusion were employed to mitigate right eye deprivation amblyopia. Eighteen months later, the patient can fixate and follow objects with the right eye. Left eye corneal transparency was restored, and bilateral IOP control was achieved. Conclusion: Despite prompt surgical treatment, acute hydrops presents a postoperative management challenge and may result in irreversible corneal scarring. Timely management of corneal opacities is crucial to prevent amblyopia. A multidisciplinary approach is essential for the best visual outcome.

Abstract Background Approximately 20 years have passed since the Person-relative-to-Event (PrE) Model of Coping with Threat was conceptualized. Despite its familiar name, this model has been under-researched. This study investigates the main assumptions of the PrE, identifies predictors of actual household earthquake adjustments in the absence of fear appeals using a non-experimental design, and proposes an alternative model: the Sequential Person-relative-to-Event Model of Coping with Threat (SPrE). Methods A survey methodology was employed with self-completed questionnaires from 822 residents of the Azores, an earthquake-vulnerable location. The associations between variables were examined. Structural Equation Modeling was applied to test the PrE and SPrE models. Results Actual household earthquake adjustment was associated with person, event, and person-relative-to-event appraisals, responsibility attributions, age, and educational level. There was a non-significant association with gender. Person-relative-to-event appraisal was a non-significant predictor of actual household earthquake adjustments and responsibility attributions did not moderate this relationship. We found that event appraisal predicted person appraisal and that its relationship with actual household earthquake adjustments was moderated by the responsibility attributions. Thus, a new hypothesis is proposed regarding the relationship between risk perception (equivalent to event appraisal) and actual household earthquake adjustments. Conclusions These results contribute to the literature, practice and cumulative scientific knowledge.

Abstract Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61–80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Plague is a deadly zoonosis that still poses a threat in many regions of the world. We combined epidemiologic, host, and vector surveillance data collected during 1961–1980 from the Araripe Plateau focus in northeastern Brazil with ecologic, geoclimatic, and Yersinia pestis genomic information to elucidate how these factors interplay in plague activity. We identified well-delimited plague hotspots showing elevated plague risk in low-altitude areas near the foothills of the plateau’s concave sectors. Those locations exhibited distinct precipitation and vegetation coverage patterns compared with the surrounding areas. We noted a seasonal effect on plague activity, and human cases linearly correlated with precipitation and rodent and flea Y. pestis positivity rates. Genomic characterization of Y. pestis strains revealed a foundational strain capable of evolving into distinct genetic variants, each linked to temporally and spatially constrained plague outbreaks. These data could identify risk areas and improve surveillance in other plague foci within the Caatinga biome.

Margarida Ribeiro,1,2,&ast; João Nogueira Freitas,3,&ast; Mário Lima-Fontes,1 Mariana Leuzinger-Dias,1 Marta Inês Silva,1 Joana Araújo,1,4 Sérgio Estrela-Silva,1,4 António Benevides Melo,1,4 João Tavares-Ferreira,1 Flávio Alves,1 João Barbosa-Breda1,4– 6 1Department of Ophthalmology, Unidade Local de Saúde de São João, Porto, Portugal; 2Department of Biomedicine – Unit of Pharmacology and Therapeutics, Faculty of Medicine of the University of Porto, Porto, Portugal; 3Faculty of Medicine of the University of Porto, Porto, Portugal; 4Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; 5UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; 6KULeuven, Research Group Ophthalmology, Department of Neurosciences, Leuven, Belgium&ast;These authors contributed equally to this workCorrespondence: Margarida Ribeiro, Department of Ophthalmology – Unidade Local de Saúde de São João, Alameda Prof. Hernâni Monteiro, Porto, 4200-319, Portugal, Email margarida.ribeiro.guimaraes@gmail.comPurpose: To evaluate the efficacy and safety of transscleral diode cyclophotocoagulation (TSCPC) at 2 years of follow up.Methods: This is a retrospective review of the records of all adult patients who underwent their first TSCPC treatment between 2014 and 2019 at Unidade Local de Saúde de São João, Porto, Portugal. Data regarding intraocular pressure (IOP), best corrected visual acuity, number of IOP-lowering medications, use of oral acetazolamide, retreatments and complications during a 2-year period following TSCPC were registered. The primary outcome was overall success at 2 years, defined as IOP≥ 6 and ≤ 21 mmHg, with at least 20% IOP reduction from baseline, with or without IOP-lowering medications (qualified and complete success, respectively), without the development of phthisis bulbi or loss of light perception due to glaucoma and no further glaucoma procedures except TSCPC retreatment.Results: Ninety-six eyes from 96 patients were included, mean age was 63 (± 14) years. Mean IOP at baseline was 39.1 (± 13.3) mmHg. Mean IOP reduction at 2 years was 18.5 (42.9%) mmHg (± 16.0, min − 16.0, max 56.0) (p < 0.001) and a significant reduction in the number of IOP-lowering medications and use of oral acetazolamide was observed. IOP reduction at 2 years was positively correlated with baseline IOP (r=0.682; p < 0.001). Overall success (including complete and qualified) was achieved in 42 patients (43.8%), with 34 (35.4%) presenting qualified success. Neovascular glaucoma (NVG) was the predominant diagnosis (n = 30, 31.3%), with a higher mean baseline IOP of 46.3 mmHg (± 11.8, min 21.0, max 70.0) and a larger mean IOP reduction at 2 years of 24.7 (51.0%) mmHg (± 16.4, min − 2.0, max 55.0). Thirteen patients (13.5%) developed persistent hypotony, eight of which converted to phthisis bulbi, of which half had NVG.Conclusion: TSCPC can be an effective IOP-lowering procedure, demonstrating a stronger effect when the preoperative IOP is highest. However, there is a wide variability in the effect (specially in eyes with NVG) and some relevant complications, including 8.3% of patients developing phthisis bulbi after 2 years of follow up.Keywords: intraocular pressure, glaucoma, ocular hypotension, transscleral cyclophotocoagulation, neovascular glaucoma, phthisis bulbi

Introduction: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and coronavirus disease 2019 (COVID-19). Objective: The objective was to identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease. Methods: In this prospective cohort study (June–August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism. Results: In total, 181 consecutive patients were stratified into three subgroups according to the genotype: Thr/Thr (n = 64), Thr/Ala (n = 96), and Ala/Ala (n = 21). The prevalence of low muscle area (MA) (< 92 cm²) was 52.5%. Low MA was less frequent in Ala/Thr patients (44.8%) than in Thr/Thr (60.9%) or Ala/Ala patients (61.9%) (P = 0.027). Multivariate logistic regression analysis confirmed that the Thr/Ala allele was associated with a reduced risk of low MA (41% to 69%) and myosteatosis (62% to 72%) compared with Thr/Thr + Ala/Ala (overdominant model). Kaplan–Meier curves Introduction: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and coronavirus disease 2019 (COVID-19). Objective: The objective was to identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease. Methods: In this prospective cohort study (June–August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism. Results: In total, 181 consecutive patients were stratified into three subgroups according to the genotype: Thr/Thr (n = 64), Thr/Ala (n = 96), and Ala/Ala (n = 21). The prevalence of low muscle area (MA) (< 92 cm²) was 52.5%. Low MA was less frequent in Ala/Thr patients (44.8%) than in Thr/Thr (60.9%) or Ala/Ala patients (61.9%) (P = 0.027). Multivariate logistic regression analysis confirmed that the Thr/Ala allele was associated with a reduced risk of low MA (41% to 69%) and myosteatosis (62% to 72%) compared with Thr/Thr + Ala/Ala (overdominant model). Kaplan–Meier curves

Background and objectiveAn important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil.MethodsWe performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]).ResultsAmong 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]).ConclusionEstradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP.Trial registrationThis trial (NCT03220152) was registered on July 18, 2017.

IntroductionForkhead box E1 (FOXE1) is a transcription factor with a crucial role in thyroid morphogenesis and differentiation. Promoter hypermethylation downregulates FOXE1 expression in different tumor types; nevertheless, its expression and relationship with methylation status in differentiated thyroid cancer (DTC) remain unclear.MethodsA total of 33 pairs of matched samples of PTC tumors and non-tumors were included. Tumor cell cultures were treated with either 5-Aza-2′-deoxycytidine demethylating agent or dimethyl sulfoxide (DMSO). A real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to assess FOXE1 expression. The methylation status was quantified using bisulfite sequencing. A luciferase gene assay was used to determine CpG-island functionality. Gene expression and promoter methylation of FOXE1 and FOXE1-regulated genes were also analyzed with data from The Cancer Genome Atlas (TCGA) thyroid samples.ResultsAfter demethylating treatment, increased FOXE1 mRNA was observed concomitantly with reduced promoter methylation of CpGisland2. A negative correlation between mRNA downregulation and an increased methylation level of CpGisland2 was observed in tumors. Diminished protein expression was also detected in some DTC cell lines and in some tumor samples, suggesting the involvement of post-transcriptional regulatory mechanisms. CPGisland2 was proved to be an enhancer. TCGA data analysis showed low FOXE1 mRNA expression in tumors with a negative correlation with methylation status and a positive correlation with the expression of most of its target genes. Reduced FOXE1 expression, accompanied by a high methylation level, was associated with PTC aggressiveness (tall cell variant, advanced extra thyroid extension, T4 American Joint Committee on Cancer (AJCC) classification), age at diagnosis (over 45 years old), and presence of a BRAFV600E mutation.ConclusionFOXE1 mRNA was downregulated in DTC compared with non-tumors, followed by high CpGisland methylation. A coupling of low mRNA expression and high methylation status was related to characteristics of aggressiveness in DTC tumors.

Objetivo: Realizar uma análise sistemática da literatura sobre o papel da ultrassonografia na punção de acesso venoso periférico, seja como parte de um protocolo obrigatório ou como recurso adicional da punção venosa. Método: Este estudo adota um protocolo de revisão de escopo, seguindo as diretrizes do Manual do Instituto Joanna Briggs –JBI (Manual for Evidence Synthesis). A confiabilidade do método de revisão será garantida por meio da consulta às bases de dados: Scopus, Web Of Science, PubMed, Embase, além do uso do Google Scholar como fonte de literatura cinzenta. A organização das referências bibliográficas será feita através do gerenciador EndNote. Após a eliminação de estudos duplicados, a escolha dos estudos será realizada por três pesquisadores livres, conforme indicado no fluxograma. O processo de seleção será minuciosamente explicado, e as informações pertinentes serão retiradas dos estudos e registradas em uma planilha criada pelos autores no Microsoft Excel. Essas informações serão interpretadas e avaliadas de acordo com os objetivos estabelecidos. Os dados serão subsequentemente estruturados em tabelas, quadros e fluxogramas, os quais serão acompanhados por uma análise narrativa.

IntroductionThe COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes.MethodsPeripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants.ResultsThe rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease.DiscussionOur findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

A difusão é o principal meio de transporte do fósforo (P) no solo e depende de vários fatores, como a interação do P com os componentes da fase sólida, a textura, a mineralogia da fração argila, a umidade, a compactação e a fonte fosfatada. Assim, dada a variação de solos no Seridó Paraibano, é de se esperar variação no fluxo difusivo de P. Objetiva-se com este estudo analisar o efeito de níveis de fósforo no fluxo difusivo de fosfato em solos representativos do Seridó Paraibano. Foram utilizadas amostras, coletadas na camada 0-20 cm de profundidade, de seis solos representativos. O experimento foi conduzido em delineamento de blocos casualizados, em fatorial 6 × 5, sendo seis solos e cinco níveis de P (0%, 10%, 20%, 30% e 40% da capacidade máxima de sorção de P). Para estimativa do fluxo difusivo de P, utilizou-se como unidades experimentais anéis de PVC com 5 cm de altura e 10 cm de diâmetro interno, com volume de solo de 300 cm3, que receberam os solos e as doses em estudo e serviram como câmara de difusão. Para avaliação do fluxo difusivo de P nos solos, utilizou-se o papel de troca aniônica (PA), que permaneceu em contato com o solo por 15 dias. Após esse período, a quantidade de P retida no PA foi quantificada. Os níveis de P promoveram o aumento do fluxo difusivo do fosfato de forma linear, com exceção do Neossolo Flúvico, no qual não foi verificada resposta significativa. O maior fluxo de P foi verificado no Planossolo (0,0753 µmol.cm-²/15 dias), seguido pelo Neossolo Regolítico (0,0510 µmol.cm-²/15 dias). O Neossolo Flúvico foi o solo que apresentou menor fluxo difusivo (0,0274 µmol.cm-²/15 dias). Conclui-se que a aplicação de P aumentou o fluxo difusivo do fosfato e que o fluxo difusivo de P foi maior no Planossolo e menor no Neossolo Flúvico.

Cancer companion diagnostics are incredibly important in helping to determine whether a patient will benefit from immune checkpoint inhibitor (ICI) treatment. Determining the chances of treatment success helps to inform clinicians to make the best treatment decisions for a particular patient. Many immune checkpoint related proteins show potential as biomarkers for ICI success, such as the checkpoint proteins themselves, cytokines, interleukins and other immune response related proteins. The most investigated checkpoint inhibitor protein is Programmed Death Ligand 1 (PD-L1), which is used as a biomarker in clinical diagnostic tests but, with some limitations. In the near future, tests for many different biomarkers will start becoming commercially available along with tests for multiple biomarkers simultaneously, giving an even better prediction of potential ICI success. Electrochemical sensors are a high sensitivity point of care diagnostic technique that can have the potential to achieve detection of multiple biomarkers at once. The main problem facing this field is improving their sensitivity to be able to detect the incredibly low concentrations of biomarkers found in liquid biopsy samples. Many methods such as enhancing an electrode surface with high conductivity materials or increasing the measured electrochemical signal via signal amplifying molecules have been investigated with promising results. This review investigates the potential biomarkers relevant to predicting ICI success, as well as the current electrochemical sensors that have been developed to determine the expression levels of these proteins.

Introdução: O carcinoma medular da tireoide é um câncer raro que se origina nas células C parafoliculares e pode ser esporádico ou hereditário. Tanto as doenças esporádicas quanto as hereditárias são causadas principalmente por mutações no proto-oncogene RET.Objetivo: Investigar variantes germinativas patogênicas do gene RET em uma coorte de pacientes com carcinoma medular da tireoide no Estado da Bahia. Método: Estudo transversal, descritivo, envolvendo pacientes com diagnóstico histopatológico de carcinoma medular da tireoide, encaminhados para testes moleculares de 2020 a 2022. Dados clínicos e patológicos foram coletados de dados médicos. O DNA genômico foi extraído do sangue periférico. Os éxons 10, 11, 13, 14 e 15 do RET foram amplificados usando a técnica de reação em cadeia da polimerase e posteriormente sequenciados usando o método de Sanger. Resultados: O estudo incluiu 29 pacientes (82,8% mulheres). A idade média no diagnóstico foi de 46,5 ± 13,1 anos, e o tamanho médio do tumor foi de 2,1 ± 1,4 cm. De acordo com a classificação TNM, 38% dos tumores foram estadiados como T1a, 27,6% como T1b, 24,1% como T2 e 10,3% como T3. Metástase linfonodal regional (N1) esteve presente em 44,8% dos casos. Metástase a distância (M1) para o mediastino foi observada em um caso (3,4%). Variantes do RET foram identificadas em 55,2% dos pacientes. A variante patogênica C634R foi identificada em um paciente (3,4%). Conclusão: Este estudo conseguiu descrever o perfil clínico e molecular de pacientes com carcinoma medular de tireoide no Estado da Bahia.

ABSTRACT Objectives: To assess the molecular profile of follicular cell-derived thyroid carcinomas (FCDTCs) and correlate the identified mutations with the clinical and pathological features of the affected patients. Materials and methods: Cross-sectional study of tumor samples from 100 adult patients diagnosed with FCDTC between 2010 and 2019. The patients’ clinical and pathological data were collected. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumors using the ReliaPrep FFPE gDNA Miniprep System. Genotyping of target genomic regions (KRAS, NRAS, BRAF, EGFR, and PIK3CA) was performed using the AmpliSeq panel, while sequencing was performed on the iSeq 100 platform. Results: The patients’ mean age was 39 years. In all, 82% of the tumors were classic papillary thyroid carcinomas. Overall, 54 (54%) tumor samples yielded satisfactory results on next-generation sequencing (NGS), of which 31 harbored mutations. BRAF gene mutations were the most frequent, with the BRAFV600E mutation present in 10 tumors. Seven tumors had BRAFNON-V600E mutations not previously described in FCDTCs (G464E, G464R, G466E, S467L, G469E, G596D, and the T599Ifs*10 deletion) but described in other types of cancer (i.e., skin/melanoma, lung, colorectal, and others). One tumor had a previously reported BRAFA598V mutation. EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed. Conclusion: We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

Introdução: As vítimas de violência por parceiro íntimo enfrentam uma gama alarmante de consequências físicas e emocionais decorrentes dessas agressões, impactando não apenas as vítimas, mas também as pessoas em seu entorno, especialmente os filhos. Objetivo: Explorar, através da análise de literatura especializada, os impactos psicossociais sobre filhos de mulheres que foram vítimas de violência por parte de seus parceiros. Método: Trata-se de uma revisão integrativa da literatura. As buscas na literatura foram conduzidas por meio descritores constantes no MeSH e no DeCS, combinados com os operadores booleanos AND e OR, realizadas na Biblioteca Virtual de Saúde e Medline via Pubmed. Resultados: Foram incluídos 10 artigos. Os estudos analisados abordam principalmente a exposição na infância e na adolescência à violência por parceiro íntimo (VPI) e suas consequências, variando de impactos no desenvolvimento físico e cognitivo até questões de saúde mental e ajustamento social. Conclusão: A análise sistemática dos artigos revelou que em círculos familiares com a presença de VPI, é notório os impactos negativos no desenvolvimento psicológico e comportamental das crianças.

Abstract This study employed e-Vol DXS cone beam computed tomography (CBCT) software to assess dentin remnants in the furcation area of mesial canals in mandibular molars during root canal retreatment (RCR). Four groups (Reciproc®, ProTaper Next®, Race Evo®, Protaper Gold®) were subjected to RCR, and CBCT images were captured before (T1) and after (T2) treatment. Measurements of remaining dentin thickness at 1 mm and 3 mm below the furcation were scrutinized. Results revealed no significant differences in mean thicknesses of mesiobuccal (MB) and mesiolingual (ML) canals at 1 mm and 3 mm from the furcation pre-treatment (T1). Post-treatment (T2) showed analogous findings, with no significant differences in mean thicknesses. However, disparities were found between MB and ML canals at both distances, both before and after retreatment. In essence, the evaluated instruments exhibited safety in RCR, implying that they are appropriate for use in critical areas of mandibular molars without inducing excessive wear. This study underscores the reliability of these instruments in navigating danger zones during RCR, and contributes valuable insights for dental practitioners who handle complex root canal scenarios in mandibular molars.

Resumo Introdução: As doenças respiratórias agudas apresentam difícil mensuração e contribuem para o grande número de causas de óbito mal definidas, o que afeta a confiabilidade das informações de mortalidade. Objetivo: Verificar a acurácia da definição da causa básica de óbito para doenças respiratórias agudas dos óbitos registrados no Sistema de Informações sobre Mortalidade do Distrito Federal em 2018. Método: Foi realizado um estudo de acurácia, com amostra mínima de 331 declarações de óbito com as causas de óbito do capítulo 10 (doenças do aparelho respiratório — J00-J99 — conforme subcategorias) da Classificação Internacional de Doenças na versão 10, considerando a definição de causa básica de óbito pela equipe de investigação como o padrão-ouro. Foram calculadas a sensibilidade, especificidade, valores preditivos positivo e negativo e as razões de verossimilhanças positivas e negativas com os respectivos intervalos de confiança a 95%. Resultados: Total de 396 declarações de óbito foram incluídas. Foi constatada alta sensibilidade para identificar doenças pulmonares agudas nas causas básicas de óbito (82,8%. IC95% 78,6–86,5) e alta especificidade (93,1%. IC95% 77,2–99,2). A probabilidade de a declaração apresentar resultado falso negativo foi baixa (0,2. IC95% 0,1–0,2). Conclusão: As declarações de óbito por doenças respiratórias agudas apresentaram bons resultados para acurácia e incitam a realização de estudos semelhantes para outras condições.

A recent pilot study in amyotrophic lateral sclerosis (ALS) patients analyzed the effect of a Mediterranean diet (MeDi) supplemented with nicotinamide riboside (NR, a NAD+ promoter), pterostilbene (PTER, a natural antioxidant) and/or coconut oil on anthropometric variables in ALS patients. The results suggested that the MeDi supplemented with NR, PTER and coconut oil is the nutritional intervention showing the greatest benefits at anthropometric levels. Over the last 30 years, glucose intolerance has been reported in ALS patients. Thus, suggesting that an alternative source of energy may be preferential for motor neurons to survive. Ketone bodies (KBs), provided through a MeDi with a lower carbohydrate content but enriched with medium chain triglycerides, could be a therapeutic alternative to improve the neuromotor alterations associated with the disease. Nevertheless, the use of a coconut oil-supplemented diet, as potentially ketogenic, is a matter of controversy. In the present report we show that a MeDi supplemented with coconut oil increases the levels of circulating KBs in ALS patients.

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians’ preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

The hornworm (Erinnyis ello) is an important pest of cassava and rubber tree with high capacity of migration and can be controlled with biological control agents such as baculoviruses. Baculoviruses are rod-shaped enveloped viruses with circular double-stranded DNA genomes infecting insects of the order Lepidoptera. Prior to large-scale use of certain baculovirus, it is essential to assess its genetic and morphological information. This work aimed to characterize the baculovirus isolate occurring in Erinnyis ello populations at small farms in Cruzeiro do Sul, Acre State, Brazil and to develop parameters for field management using this isolate. Viral particles were purified from infected larvae through ultracentrifugation in sucrose gradient. After treatment and negative staining with uranyl acetate 2%, viral particles were visualized using transmission electron microscope. The virus with ovicylindrical occlusion body presenting only one virion per envelope and size less than 0.5 μm was identified as a member of the genus Betabaculovirus. Viral DNA was extracted through phenol/chloroform cycles, digested with different restriction enzymes and separated with agarose gel electrophoresis. The restriction enzyme patterns obtained with the enzymes Bam HI and Hind III revealed seven and three DNA fragments, respectively; cleavage with Pst I, generated eight molar fragments and three submolar fragments and Eco RI digestion resulted in 21 fragments, with some submolar bands. Comparison of the DNA restriction pattern from ErelGV isolated in Acre with that described for ErelGV isolated from SC State showed high similarity. This isolate named as ErelGV-Acre presented potential for control of E. ello populations.

Abstract Protein preconcentration is an essential sample preparation step for analysis in which the targeted proteins exist in low concentrations, such as bodily fluids, water, or wastewater. Nonetheless, very few practical implementations of miniaturized protein preconcentration devices have been demonstrated in practice, and even fewer have been integrated with other microanalytical steps. Existing approaches rely heavily on additional chemicals and reagents and introduce complexity to the overall assay. In this paper, we propose a novel miniaturized isoelectric focusing-based protein preconcentration screening device based on electrochemically derived pH gradients rather than existing chemical reagent approaches. In this way, we reduce the need for additional chemical reagents to zero while enabling device incorporation in a seamlessly integrated full protein analysis microsystem via Lab-on-PCB technology. We apply our previously presented Lab-on-PCB approach to quantitatively control the pH of a solution in the vicinity of planar electrodes using electrochemical acid generation through redox-active self-assembled monolayers. The presented device comprises a printed circuit board with an array of gold electrodes that were functionalized with 4-aminothiophenol; this formed a self-assembled monolayer that was electropolymerized to improve its electrochemical reversibility. Protein preconcentration was performed in two configurations. The first was open and needed the use of a holder to suspend a well of fluid above the electrodes; the second used microfluidic channels to enclose small volumes of fluid. Reported here are the resulting data for protein preconcentration in both these forms, with a quantitative concentration factor shown for the open form and qualitative proof shown for the microfluidic.

Background/Objectives: The aim of this study was to evaluate incidental findings in the mandible after the placement of dental implants using a new cone–beam computed tomography (CBCT) software. Methods: The initial sample consisted of 2872 CBCT scans of patients of both sexes. The parameters evaluated in this study were the location of the implants in the mandible, implant length, anatomical relationship of the implant with the mandibular canal, presence or absence of damage to the adjacent teeth, presence or absence of implant fractures, and presence or absence of bone support. Fisher’s exact test was performed to compare the variables. The significance level was set at p = 0.05. Results: Out of 2872 CBCT scans, 214 images of patients with an average age of 44.5 years were included. The most frequent location of the implants was the posterior region (93.5%), with 54% of the implants having a length between 9 and 14 mm. It was found that 92% of the implants were positioned above the mandibular canal. Damage to adjacent teeth was observed, with no correlation with the implant positioning (p = 1.000). In 100% of cases of implants in the anterior region, there was bone support. Fracture was observed in 1.7% of implants with a length between 9 and 14 mm. Conclusions: The installation of implants in the mandible occurs more frequently in the posterior region, with a high presence of bone support and a low incidence of damage to adjacent teeth, anatomical structures, and fractures.

International mobility of higher education institutions' members within the European Union is explicitly encouraged and used as one of the higher education institutions' quality criteria. This paper aims to contribute to the analysis of the phenomenon of international mobility between higher education institutions, especially within the European area in the broad sense, and for which the ERASMUS+ Programme is paradigmatic. The authors have been linked to mobility processes by addressing issues of internationalisation and receiving and sending students and teachers in and out of their institution, and/or hosting them in curricular units taught by them or in other training actions. It is in this context that theoretical reflection has been carried out, to respond to the objective of analysing the relevance of mobility in the internationalisation of higher education institutions and to reflect on questions of its evaluation. It is concluded that there is interest in allowing a mutually enriching scientific dialogue for the personal and professional development of those involved -- students, academics and other staff members. Furthermore, it is institutionally considered that the higher education institution is promoting its quality and image if it provides an in-depth exchange of ideas and practices that foster improvements in teaching and research of the institutions involved. It is also concluded that there is a need for structures to respond to this new reality and that the evaluation processes can contribute to measuring and promoting it.

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.