Abstract Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines. crossreactivity cross reactivity flaviviruses immunodiagnostics threedimensional three dimensional structure rDMEC rDME C rDMEBR. rDMEBR BR. BR linker carboxyterminal carboxy terminal histidine tag 1683 16 83 16.8 1680 80 respectively 635 35 6.35 proteome 200 2019 testing 1 µgmL µg mL 3 rDMEC, C, 150 50 1:5 1100. 1100 100. 100 1:100 patients inhouse house 773 77 77. 826 82 82. 894 89 4 89. 714 71 71. rDEMBR rDEM Zikainfected COVID19 COVID 19 COVID-1 samples Denguespecific specific vaccines 168 8 16. 63 6.3 20 201 15 5 1: 110 1:10 7 COVID1 COVID- 6. 2 11 1:1

Resumo O tratamento da epilepsia avançou nos últimos 30 anos com o desenvolvimento de novos medicamentos anticrise (MAC). Infelizmente, nem todos estão aprovados no Brasil e muitos ainda são subutilizados. Os novos MAC não são mais eficazes que os antigos, mas apresentam melhor tolerabilidade, menos interações e efeitos colaterais a longo prazo, especialmente para pacientes com comorbidades ou que necessitam de politerapia. A indução enzimática causada pelos MAC antigos está associada ao aumento dos níveis de colesterol, interações medicamentosas com redução do efeito das estatinas e outros medicamentos cardiovasculares, anticoagulantes, quimioterapia, imunossupressores, agentes anti-infecciosos (incluindo tratamento do HIV), antidepressivos e contraceptivos. Além disso, podem reduzir os níveis de vitamina D e hormônios sexuais, podendo afetar a massa óssea. A crescente preocupação sobre estes efeitos ao longo da vida, com a exposição prolongada, levou a maioria dos países desenvolvidos a modificar o padrão de prescrição com maior uso dos novos MAC, especialmente levetiracetam e lamotrigina. Ambos são considerados as opções mais seguras para mulheres em idade fértil. Infelizmente, as tendências de prescrição no Brasil permaneceram praticamente inalteradas ao longo do tempo. Isto pode ser parcialmente explicado pela lentidão no processo de aprovação dos MAC e à resistência dos médicos generalistas e neurologistas em adotar estes novos conceitos. Nesta revisão, destacamos as vantagens dos novos MAC e a necessidade da mudança no padrão de prescrição também no Brasil. A escolha do MAC deve ser feita de acordo com as características individuais dos pacientes e sugestões práticas são apresentadas. 3 MAC. . (MAC) Infelizmente subutilizados tolerabilidade prazo politerapia colesterol cardiovasculares anticoagulantes quimioterapia imunossupressores antiinfecciosos anti infecciosos incluindo HIV, HIV , HIV) contraceptivos disso sexuais óssea vida prolongada lamotrigina fértil tempo conceitos revisão apresentadas (MAC

Abstract The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper. 3 ASMs. . (ASMs) Unfortunately underused ones However tolerability longterm long term polytherapy anticoagulants chemotherapy immunosuppressors antiinfective anti infective including treatment, , treatment) antidepressants contraceptives Additionally hormones density life exposure lamotrigine age Regrettably time concepts review characteristics paper (ASMs

Abstract The aim of this study was to compare the quantification of hard-tissue debris by using micro-computed tomography (micro-CT) and nano-focus computed tomography (nano-CT) after root canal instrumentation. Ten mandibular molars containing an isthmus in the mesial root were scanned in a SkyScan 1172 micro-CT device with a voxel size of 12.8 µm and in a NanoTom nano-CT device with 5.5 µm. The mesial root canals were irrigated with 5 mL of saline solution at the orifice level, instrumented with Reciproc R25 files and a second scanning was performed by micro-CT and nano-CT devices for post-instrumentation images. DataViewer software was used for registering the pre- and post-operative micro-CT and nano-CT images. The root canal and the debris were segmented for quantitative analysis of the volume of the canal and volume of debris using CTAn software. Statistical analysis was performed using the T test for comparison between volume of the canal after instrumentation and volume of debris in both image modalities. The level of significance was set at p < 0.05. Nano-CT images showed higher values of debris when compared with micro-CT (p < 0.05) after root canal instrumentation. No difference was observed between the volume of the root canal after instrumentation in the two imaging methods used (p > 0.05). Nano-CT technology can be recommended as a more precise method for quantitative analysis of hard-tissue debris. Moreover, in Endodontic research it is a promising method, as it is capable of providing higher spatial and contrast resolution, faster scanning and higher image quality. hardtissue hard tissue microcomputed micro microCT CT (micro-CT nanofocus nano focus nanoCT (nano-CT 117 128 12 8 12. 55 5. R R2 postinstrumentation post pre postoperative operative modalities 005 0 05 0.05 NanoCT Nano . Moreover resolution quality 11 1 00 0.0 0.

Abstract Objective To analyze the experiences and meanings of intimate relationships experienced by women in treatment due to drug consumption. Method This was a qualitative, descriptive and cross-sectional study developed with the participation of 21 women attended at a Psychosocial Care Center in the state of São Paulo, Brazil. The interviews were submitted to reflective thematic analysis and organized into three axes. Results The women reported lifelong social vulnerabilities and weaknesses in support networks that led to suffering, helplessness, and early drug use. Becoming a wife was constructed as a hope for a new way of life, though in an idealized and contrived manner. Intimate relationships proved to be central, both for experiences of increased and decreased drug use. Drug use escalated due to the need to please the partner, fulfill the role of a wife, or when faced with violence. Decreases occurred in situations where the partner provided support, assistance in accessing treatment, or when the spouse restricted their freedom. These relationships added to the vulnerabilities experienced, creating demands on healthcare and social systems. Conclusion Treatment should include interventions regarding women’s intimate relationships, as well as addressing gender roles and intervening intersectorially in other social determinants. consumption qualitative crosssectional cross sectional 2 Paulo Brazil axes suffering helplessness life manner central violence freedom systems womens s determinants

Resumo Objetivo Analisar as vivências e significados dos relacionamentos afetivo-amorosos vivenciados por mulheres em tratamento devido ao consumo de drogas. Método Pesquisa qualitativa, descritiva e transversal desenvolvida com a participação de 21 mulheres atendidas em um Centro de Atenção Psicossocial do interior paulista. As entrevistas foram submetidas à análise temática reflexiva e organizam-se em três eixos. Resultados As mulheres relataram vulnerabilidades sociais ao longo da vida e fragilidades nas redes de apoio que culminaram em sofrimentos, desamparo e uso precoce de drogas. Tornar-se esposa foi construído como esperança para um novo modo de vida, porém de forma idealizada e engendrada. As relações afetivas mostraram-se centrais, tanto para experiências de aumento como de diminuição do consumo de drogas. O uso aumentou por necessidade de agradar o parceiro, cumprir o papel de esposa ou diante das violências. A diminuição ocorreu em situações de apoio do companheiro, auxílio para acessar o tratamento ou quando cônjuge restringiu sua liberdade. Esses relacionamentos se somaram às vulnerabilidades vividas produzindo demandas aos equipamentos de saúde e sociais. Conclusão O tratamento deve incluir intervenções sobre os relacionamentos amorosos das mulheres, assim como problematizar os papéis de gênero e interpor-se intersetorialmente entre os demais determinantes sociais. afetivoamorosos afetivo drogas qualitativa 2 paulista organizamse organizam eixos sofrimentos Tornarse Tornar engendrada mostraramse mostraram centrais parceiro violências companheiro liberdade interporse interpor

Resumen Los sesgos de respuesta son problemas en los inventarios de la psicología organizacional positiva. El estudio tiene como objetivo controlar el sesgo de respuesta en la evaluación del trabajo significativo a través de dos métodos: ítems clave invertidos y formato de elección forzosa. La muestra estuvo formada por 351 profesionales; las mujeres constituyeron el 60.0 % de la muestra. Los participantes respondieron dos versiones del instrumento de significado del trabajo: ítems tipo Likert y elección forzosa. Para ambas versiones, el modelo unifactorial fue el más apropiado para los datos disponibles. Los resultados indican que el modelo de intersecciones aleatorias se ajusta a los datos Likert (CFI = .92), así como al modelo de elección forzada (CFI = .97). Además, la dimensión latente de la versión de elección forzada no se correlacionó con el índice de aquiescencia (r < .08; p > .05), y aproximadamente el 20 % de la varianza de los ítems podría deberse al método (Likert o forzado). elección). El presente estudio ilustra la importancia del control del sesgo de respuesta en los instrumentos de autoinforme.

Abstract Response biases are issues in inventories in positive organizational psychology. The study aims to control the response bias in the assessment of meaning of work through two methods: reversed key items and forced-choice format. The sample consisted of 351 professionals; women constituted 60.0 % of the sample. The participants answered two versions of the instrument for meaning of work: Likert-type items and forced-choice. For both versions, the unifactorial model was the most appropriate for the data available. The results indicate that the random intercepts model fit the Likert data (CFI = .92), as well as the forced-choice model (CFI = .97). Besides, the latent dimension of the forced-choice version did not correlate with acquiescence index (r < .08; p > .05), and approximately 20 % of the variance of the items might be due to the method (Likert or forced-choice). The present study illustrates the importance of response bias control in self-report instruments.

Abstract Employees’ perceived opportunities to craft (POCs) influence actual job crafting behavior, which may have consequences for their well-being and work performance. This study aimed to validate the perceived opportunities to craft scale (POCS) in the Brazilian context. We collected data from Brazilian employees (N = 1451) in two separate samples. The factor structure, reliability, and convergent validity of the POCS were tested using confirmatory factor analysis (CFA), multigroup confirmatory factor analysis (MGCFA), and external variables. The results indicated that the POCS-Brazilian version (with seven-point and five-point Likert scale) replicated the unidimensional structure of the original instrument. POCs showed significant positive and moderate correlations with occupational self-efficacy, work engagement and job crafting, and negative associations with workaholism. Both POCS-Brazilian versions were reliable according to three types of reliability indexes and also showed discriminant and convergent validity evidence.

Research in cognitive psychology has emphasized that the body's position in space and patterns of visual searching for stimuli are crucial variables to explain the ability to estimate distances numerically. In this paper, we tested the hypothesis that proprioception recalibration interferes in the ability to numerically estimate fixed peri-personal space. The Rubber Hand Illusion (RHI) experimental paradigm was applied as a tool to temporally manipulate the sense of proprioception in participant's right hand. Seventeen college students were asked to estimate horizontal fixed spatial cues before and after two conditions of tactile stimulation within RHI (synchronous versus asynchronous stroking). Results evidenced that proprioceptive recalibration of the hand were temporally altered by both stroking patterns. However, the effects of numerically estimate fixed horizontal cues towards the body midline were only consistently observed in the synchronous stroking condition. These findings suggest that numerical estimates of peripersonal fixed cues are strongly associated with proprioceptive recalibration, corroborating the literature on multisensory integration of perception.

La literatura en psicología cognitiva ha enfatizado que la posición del cuerpo en el espacio y los patrones de búsqueda visual de estímulos son variables cruciales para explicar la capacidad de estimar distancias numéricamente. En este artículo, hemos probado la hipótesis de que la recalibración de la propiocepción interfiere en la capacidad de estimar numéricamente el espacio peri-personal fijo. El paradigma experimental Rubber Hand Illusion (RHI) se aplicó como herramienta para manipular temporalmente el sentido de propiocepción en la mano derecha del participante. Se pidió a diecisiete estudiantes universitarios que, dentro de la RHI, estimasen señales espaciales fijadas horizontalmente antes y después de dos condiciones de estimulación táctil (estimulaciones síncronas x asíncronas). Los resultados evidenciaron que la recalibración proprioceptiva de la mano fue temporalmente alterada por ambos patrones de estimulación. Sin embargo, los efectos de estimar las señales fijas numéricamente en dirección de la línea media del cuerpo sólo fueron observados consistentemente en la condición de estimulación síncrona. Estos resultados sugieren que la estimación numérica de señales fijas peripersonales está fuertemente asociadas con la recalibración proprioceptiva, corroborando la literatura sobre integración multisensorial de la percepción.

Onychomychosis, a nail fungus infection is the most frequent nail ailment, constituting about half of all nail disorders. It can be caused by dermatophytes, non-dermatophytes, yeasts and Prothoteca spp. Methods include 5407 samples of patients with suspected onychomycosis, studied from January 2002 to December 2006, by direct mycological examination and fungi culture. The diagnosis of onychomycosis was confirmed in samples from 3822 direct mycological and/or culture positive. The diagnosis was established by culture for fungi. Among the 1.428 identified agents, the dermatophytes were responsible for 68.6% (N = 980) of cases, followed by yeasts with 27.6% (N = 394), non-dermatophytes fungi with 2.2% (N = 31), Prothoteca spp with 0.1% (N = 2), and associations with 1.5% (N = 22). Females were more affected, with 66% (N = 2527) of cases, and the most affected age group ranged from 31 to 60 years of age (median 47 years). Fungal microbiota is often changed in the world, both quantitatively and qualitatively, and is affected by several environmental factors. Thus, the periodic review of the composition of this microbiota is important to evaluate the epidemiology and thus proportion a better therapeutic response.

Este estudo objetivou avaliar a imunoexpressão dos transportadores de glicose 1 (GLUT-1) e 3 (GLUT-3) em carcinomas de células escamosas de lábio inferior (CCELI) metastáticos e não-metastáticos. Vinte CCELIs com metástase nodal regional e 20 CCELI sem metástase foram selecionados. Foram analisados a distribuição da imunomarcação e o percentual de imunorreatividade para GLUT-1 e GLUT-3 no centro tumoral e no front de invasão tumoral. A maioria dos tumores (70%) revelou marcação para GLUT-1 em áreas periféricas dos ninhos, lençóis e ilhas de células neoplásicas, ao passo que GLUT-3 revelou predomínio de marcação em áreas centrais (72.5%). Um alto percentual de células positivas para GLUT-1 foi observado no front de invasão e no centro tumoral das lesões metastáticas e não-metastáticas (p>0,05). O percentual de células positivas para GLUT-1 foi superior ao percentual de células positivas para GLUT-3, tanto no front de invasão (p<0,001) quanto no centro tumoral (p<0,001) dos CCELIs. Não foram observadas diferenças significativas no percentual de células positivas para GLUT-1 e GLUT-3 em relação à mestástase nodal, ao estádio clínico ou ao grau histológico de malignidade (p>0,05). Em conclusão, os resultados do presente estudo sugerem um importante papel para GLUT-1 na absorção de glicose nos CCELIs, embora esta proteína não pareça estar envolvida na progressão destes tumores. Por outro lado, a expressão de GLUT-3 pode representar um mecanismo secundário para a absorção de glicose nos CCELIs.

This study aimed to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastasis were selected. The distribution of staining and the percentage of GLUT-1 and GLUT-3 staining in each tumor core and at the deep invasive front were assessed. Most tumors (70%) exhibited peripheral staining for GLUT-1 in nests, sheets and islands of neoplastic cells, whereas predominantly central staining was observed for GLUT-3 (72.5%). A high percentage of GLUT-1-positive cells was observed at the deep invasive front and in the tumor core of metastatic and non-metastatic tumors (p>0.05). The percentage of GLUT-1-positive cells was much higher than that of GLUT-3-positive cells both in the deep invasive front (p<0.001) and in the tumor core (p<0.001) of LLSCCs. No significant differences in the percentage of GLUT-1- and GLUT-3-positive cells were observed according to nodal metastasis, clinical stage or histological grade of malignancy (p>0.05). In conclusion, the results of the present study suggest an important role of GLUT-1 in glucose uptake in LLSCCs, although this protein does not seem to be involved in the progression of these tumors. On the other hand, GLUT-3 expression may represent a secondary glucose uptake mechanism in LLSCCs.

Embora sejam morfologicamente semelhantes, os hemisférios cerebrais apresentam diferenças funcionais geneticamente determinadas. Ainda assim, anormalidades eletrencefalográficas focais deveriam ocorrer simetricamente numa população geral, embora a literatura tenha referido um predomínio à esquerda. Nosso objetivo é relatar o primeiro estudo latino-americano sobre uma grande série de EEGs, no intuito de observar se há lateralização de anormalidades focais. MÉTODO: Foram estudados retrospectivamente 10.408 EEGs, realizados de abril de 2001 a abril de 2010, os quais foram classificados de acordo com a presença de anormalidades focais específicas (descargas) e inespecíficas (ondas lentas focais). Os EEGs foram divididos de acordo com o gênero e a idade, e foram analisados achados clínicos associados. RESULTADOS: As descargas foram mais prevalentes no hemisfério cerebral esquerdo, no lobo temporal, observando-se uma lateralização mais forte entre os adultos. À direita, elas prevaleceram no lobo frontal. Ondas lentas focais prevaleceram também à esquerda e no lobo temporal, especialmente entre os adultos. Entre os que apresentaram ondas lentas à esquerda, observou-se maior prevalência entre as mulheres. Os homens prevaleceram entre os que apresentaram ondas lentas à direita. À esquerda, ondas lentas prevaleceram nos lobos temporal e parietal. À direita, nos lobos frontal e occipital. Epilepsia foi o achado clínico mais associado à presença de descargas em ambos os hemisférios cerebrais. Ondas lentas à direita foram mais associadas a epilepsia, enquanto que, à esquerda, elas foram mais associadas a cefaleia. CONCLUSÃO: Houve diferenças entre os hemisférios cerebrais quanto à lateralização das anormalidades focais, assim como entre os gêneros, faixas etárias analisadas e quadro clínico associado.

Left and right cerebral hemispheres are morphologically similar, although they are functionally different. Focal EEG abnormalities should appear with an equal frequency in both of them, but the literature has reported a left predominance. We presented the first Latin American study on lateralization of focal EEG abnormalities. METHOD: We retrospectively studied 10,408 EEGs from April 2001 to April 2010. They were separated by age and gender to estimate the frequency of left-sided versus right-sided focal abnormalities (discharges or slow waves). Associated clinical features were also accessed. RESULTS: Discharges were more prevalent in left cerebral hemisphere, in temporal lobe, and a stronger lateralization was found among adults. Right-sided discharges occurred more in frontal lobe. Slow waves were also more prevalent in the left cerebral hemisphere and among adults. Among left-sided slow waves group, women were more prevalent. Contrarily, men were more observed among right-sided slow waves EEGs. Left-sided slow waves were more prevalent in temporal and parietal lobes. Contrarily, right-sided slow waves occurred more in frontal and occipital lobes. Epilepsy was the most frequent disease among the patients with focal discharges in both cerebral hemispheres. Right-sided slow waves were more associated to epilepsy, and left-sided slow waves were more associated to headache. CONCLUSION: There were significant differences between cerebral hemispheres on focal EEG abnormalities, considering lateralization, gender, age and clinical features. These results suggest a neurofuncional asymmetry between cerebral hemispheres which may be explained by different specificities, as well as by cerebral neuroplasticity.