HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Brazilian Guideline on Menopausal Cardiovascular Health ­ 2024 / Guía Brasileña de Salud Cardiovascular en el Climaterio y la Menopausia ­ 2024 / Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa ­ 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.

Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.

As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios "bioidênticos" "manipulados", e a 'modulação hormonal' não são recomendados pela falta de evidência científica de sua eficácia e segurança.

Understanding yeast shells: structure, properties and applications.

Background and purpose: The employment of yeasts for biomedical purposes has become increasingly frequent for the delivery of prophylactic and therapeutic products. Its structural components, such as ß-glucans, mannan, and chitin, can be explored as immunostimulators that show safety and low toxicity. Besides, this system minimizes antigen degradation after administration, facilitating the delivery to the target cells. Review approach: This review sought to present molecules derived from yeast, called yeast shells (YS), and their applications as carrier vehicles for drugs, proteins, and nucleic acids for immunotherapy purposes. Furthermore, due to the diversity of information regarding the production and immunostimulation of these compounds, a survey of the protocols and immune response profiles generated was presented. Key results: The use of YS has allowed the development of strategies that combine efficiency and effectiveness in antigen delivery. The capsular structure can be recognized and phagocytized by dendritic cells and macrophages. In addition, the combination with different molecules, such as nanoparticles or even additional adjuvants, improves the cargo loading, enhancing the system. Activation by specific immune pathways can also be achieved by different administration routes. Conclusion: Yeast derivatives combined in different ways can increase immunostimulation, enhancing the delivery of medicines and vaccine antigens. These aspects, combined with the simplicity of the production steps, make these strategies more accessible to be applied in the prevention and treatment of various diseases.

Angiotensin-(1-7) Treatment Early in Life Prevents Cardiac Hypertrophy in Adult Hypertensive Rats.

ABSTRACT: Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Prepuberty has been considered as a later susceptible window of development, and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the prepuberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHRs). SHRs were treated with Ang-(1-7) (24 µg/kg/h) from age 4 to 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography up to 17th week. Thereafter, echocardiography was performed, and the rats were euthanized for the collection of tissues and blood. Ang-(1-7) did not change the systolic blood pressure but reduced the septal and posterior wall thickness, and cardiomyocyte hypertrophy and fibrosis in SHR. In addition, Ang-(1-7) reduced the gene expression of atrial natriuretic peptide and brain natriuretic peptide, increased the metalloproteinase 9 expression, and reduced the extracellular signal-regulated kinases 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, AT1, and AT2. The treatment with Ang-(1-7) decreased the malondialdehyde (MDA) levels and increased superoxide dismutase-1 and catalase activities and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for 3 weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. In addition, this study supports the prepuberty as an important programming window.

RNA Vaccines: Yeast as a Novel Antigen Vehicle.

In the last decades, technological advances for RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle. Among the systems, yeasts emerge as a new approach, already employed to deliver protein antigens, with efficacy demonstrated through preclinical and clinical trials. ß-glucans and mannans in their walls are responsible for the adjuvant property of this system. Yeast ß-glucan capsules, microparticles, and nanoparticles can modulate immune responses and have a high capacity to carry nucleic acids, with bioavailability upon oral immunization and targeting to receptors present in antigen-presenting cells (APCs). In addition, yeasts are suitable vehicles for the protection and specific delivery of therapeutic vaccines based on RNAi. Compared to protein antigens, the use of yeast for DNA or RNA vaccine delivery is less established and has fewer studies, most of them in the preclinical phase. Here, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing the current challenges and prospects of this promising strategy.

Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment.

The understanding of the relationship between immunological responses and cancers, especially those related to HPV, has allowed for the study and development of therapeutic vaccines against these neoplasias. There is a growing number of studies about the composition and influence of the tumor microenvironment (TME) in the progression or establishment of the most varied types of cancer. Hence, it has been possible to structure immunotherapy approaches based on therapeutic vaccines that are even more specific and directed to components of TME and the immune response associated with tumors. Among these components are dendritic cells (DCs), which are the main professional antigen-presenting cells (APCs) already studied in therapy strategies for HPV-related cancers. On the other hand, tumor-associated macrophages are also potential targets since the profile present in tumor infiltrates, M1 or M2, influences the prognosis of some types of cancer. These two cell types can be targets for therapy or immunomodulation. In this context, our review aims to provide an overview of immunotherapy strategies for HPV-positive tumors, such as cervical and head and neck cancers, pointing to TME immune cells as promising targets for these approaches. This review also explores the potential of immunotherapy in cancer treatment, including checkpoint inhibitors, cytokine immunotherapies, immunotherapy vaccines, and cell therapies. Furthermore, it highlights the importance of understanding the TME and its effect on the design and achievement of immunotherapeutic methods.

Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.

Individual differences in the effects of midazolam on anxiety-like behavior, learning, reward, and choice behavior in male mice.

Introduction: The aim of the present study was to investigate the behavioral effects of the benzodiazepine midazolam in male mice, in models of anxiolysis, learning, and abuse-related effects. Methods: In a first set of experiments, male Swiss mice were submitted to the training session of a discriminative avoidance (DA) task on the elevated plus maze to evaluate anxiety-like behavior and learning after vehicle or midazolam (1, 2 or 5 mg/kg, i.g.) administration. The same animals were submitted to a conditioned place preference (CPP) protocol with midazolam (1, 2 or 5 mg/kg, i.g.). In a second experiment, outbred (Swiss) and inbred (C57BL/6) male mice were submitted to a two-bottle choice (TBC) oral midazolam drinking procedure. Animals were exposed to one sucrose bottle and one midazolam (0.008, 0.016 or 0.032 mg/ml) plus sucrose bottle. Results: Midazolam (1 and 2 mg/kg) induced anxiolytic-like effects, and all doses of midazolam prevented animals from learning to avoid the aversive closed arm during the DA training session. Assessment of midazolam reward via the CPP procedure and choice via the TBC procedure showed notable variability. A 2-step cluster analysis for the CPP data showed that midazolam data were well-fitted to 2 separate clusters (preference vs. aversion), albeit with the majority of mice showing preference (75%). Correlational and regression analyses showed no relationship between midazolam reward and anxiolytic-like effects (time spent in the open arms in the DA test) or learning/memory. Two-step cluster analysis of the TBC data also demonstrated that, regardless of strain, mice overall fell into two clusters identified as midazolam-preferring or midazolam-avoiding groups. Both midazolam preference and avoidance were concentration-dependent in a subset of mice. Discussion: Our findings show that midazolam preference is a multifactorial behavior, and is not dependent solely on the emergence of therapeutic (anxiolytic-like) effects, learning impairments, or on genetic factors (inbred vs. outbred animals).

Green nanotechnology for the development of nanoparticles based on alginate associated with essential and vegetable oils for application in fruits and seeds protection.

Aiming to highlight the valorization of the natural products and the green synthesis processes, this work describes the development of a nanoscale system based on the use of alginate to encapsulate a blend of oils (vegetable and essential oils), not previously reported, with antibacterial and antioxidant actions. The study shows the influence of the polymer and surfactant concentrations on the physicochemical properties of the nanoparticles. The formulations were characterized by DLS, zeta potential, efficiency of encapsulation and stability. In addition, the antioxidant and antimicrobial properties of the systems were evaluated using the DPPH method and disk diffusion assays, respectively. The shelf life was studied by coating fruits and seeds. The results showed that the nanostructured system was stable, the efficiency of encapsulation was high and the nanoparticles size range was about 200-400 nm. The coating of fruits and seeds showed that the system was capable of inhibiting the growth of microorganisms and delaying the fruit maturation, indicating its potential for prolonging the shelf-life of fresh food.

Health and Self-Care from the Perspective of Institutionalized Adolescents / Saúde e Autocuidado na Perspectiva de Adolescentes Institucionalizadas / La Salud y el Autocuidado desde la Perspectiva de Adolescentes Institucionalizadas

Abstract The health of institutionalized adolescents is permeated by peculiarities that are influenced by the different contexts in which they develop. This study aimed to understand the conceptions about health and self-care elaborated by adolescents under protective measures of institutional shelter, in the light of the Bioecological model. This is a qualitative and exploratory study, based on the Bioecological Theory. Fourteen adolescent girls participated in the study. Based on the ecological insertion methodology, data were collected from a field diary, medical records, a questionnaire, and semi-structured interviews, subjected to thematic content analysis. A plurality of understandings about health and self-care was verified, which are more associated with the institutional experience than with family life and evidenced a lack of actions that support healthcare habits and autonomy of adolescents within the family unit.

Resumo A saúde da adolescente institucionalizada é permeada por peculiaridades que são influenciadas pelos diferentes contextos em que se desenvolve. Este estudo teve como objetivo compreender as concepções sobre saúde e autocuidado com a saúde elaboradas por adolescentes em medida protetiva de acolhimento institucional, à luz do modelo Bioecológico. Estudo qualitativo e exploratório, embasado na Teoria Bioecológica. Participaram 14 adolescentes do sexo feminino. A partir da inserção ecológica os dados foram coletados por diário de campo, prontuário, questionário e entrevistas semiestruturadas, submetidas à análise temática do conteúdo. Verificou-se uma pluralidade de compreensões sobre saúde e autocuidado, que estão mais associadas à vivência institucional do que à convivência familiar e evidenciaram carência de ações que apoiem os hábitos de cuidados com a saúde e a autonomia das adolescentes dentro do núcleo familiar.

Resumen La salud de la adolescente institucionalizada tiene peculiaridades que están influenciadas por los diferentes contextos en los que se desarrollan. Este estudio tuvo como objetivo comprender las concepciones sobre la salud y el autocuidado de la salud elaboradas por las adolescentes en medidas de protección del acogimiento institucional, a la luz del modelo Bioecológico. Este es un estudio cualitativo y exploratorio, basado en la Teoría Bioecológica. Participaron 14 adolescentes mujeres. A partir de la inserción ecológica, los datos fueron recolectados mediante diario de campo, fichas médicas, cuestionario y entrevistas semiestructuradas, sometidas a análisis de contenido temático. Se verificó una pluralidad de comprensiones sobre la salud y el autocuidado, que están más asociadas a la experiencia institucional que a la vida familiar y mostraron una falta de acciones que apoyen los hábitos de cuidado de la salud y la autonomía de las adolescentes dentro del núcleo familiar.

Third-Generation Vaccines: Features of Nucleic Acid Vaccines and Strategies to Improve Their Efficiency.

Gene immunization comprises mRNA and DNA vaccines, which stand out due to their simple design, maintenance, and high efficacy. Several studies indicate promising results in preclinical and clinical trials regarding immunization against ebola, human immunodeficiency virus (HIV), influenza, and human papillomavirus (HPV). The efficiency of nucleic acid vaccines has been highlighted in the fight against COVID-19 with unprecedented approval of their use in humans. However, their low intrinsic immunogenicity points to the need to use strategies capable of overcoming this characteristic and increasing the efficiency of vaccine campaigns. These strategies include the improvement of the epitopes' presentation to the system via MHC, the evaluation of immunodominant epitopes with high coverage against emerging viral subtypes, the use of adjuvants that enhance immunogenicity, and the increase in the efficiency of vaccine transfection. In this review, we provide updates regarding some characteristics, construction, and improvement of such vaccines, especially about the production of synthetic multi-epitope genes, widely employed in the current gene-based vaccines.

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems.

Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used-due to its impact on the immune response and desired final effect.

Risk of Collapse in Water Quality in the Guandu River (Rio de Janeiro, Brazil).

The Guandu River, one of the main rivers in the state of Rio de Janeiro, provides water for more than nine million people in the metropolitan region. However, the Guandu has suffered from massive domestic and industrial pollution for more than two decades, leading to high levels of dissolved total phosphorus, cyanobacteria, and enteric bacteria observed during the summers of 2020 and 2021. The use of Phoslock, a palliative compound, was not effective in mitigating the levels of phosphorus in the Guandu River. Furthermore, potable water driven from the river had levels of 2-MIB/geosmin and a mud smell/taste. With all these problems, several solutions are proposed for improving the Guandu River water quality, including establishment of (i) sewage treatment plants (STPs), (ii) strict water quality monitoring, (iii) environmental recovery (e.g., reforestation), and (iv) permanent protected areas. The objective of this paper is to verify the poor water quality in the Guandu and the ineffectiveness and undesired effects of Phoslock.

Fanconi anemia and hematopoietic stem cell transplant as risk factors for oral squamous cell carcinoma: A case report with a 12-year follow-up.

Fanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer. Currently, hematopoietic stem cell transplant (HSCT) is the only curative treatment available for bone marrow failure; however, HSCT increases oral squamous cell carcinoma (OSCC) risk. Here we report the case of a patient diagnosed with Fanconi anemia in childhood who was treated with HSCT and later diagnosed with multiple OSCCs during a 12-year follow-up. Despite multiple surgical interventions and radiotherapy regimens, the patient`s health deteriorated. Management of individuals with Fanconi anemia is challenging and must be provided by a multidisciplinary healthcare team to ensure better staging, treatment planning, and coordination.

Mangrove microbiome reveals importance of sulfur metabolism in tropical coastal waters.

Mangroves under macro-tidal regimes are global carbon sequestration hotspots but the microbial drivers of biogeochemical cycles remain poorly understood. Here, we investigate the drivers of mangrove microbial community composition across a porewater-creek-estuary-ocean continuum. Observations were performed on the Amazon region in one of the largest mangrove systems worldwide with effective sequestration of organic carbon buried in soils and dissolved carbon via outwelling to the ocean. The potential export to the adjacent oceanic region ranged from 57 to 380 kg of dissolved and particulate organic carbon per second (up to 33 thousand tons C per day). Macro tides modulated microbial communities and their metabolic processes, e.g., anoxygenic phototrophy, sulfur, and nitrogen cycling. Respiration, sulfur metabolism and dissolved organic carbon (DOC) levels were linked to functional groups and microbial cell counts. Total microbial counts decreased and cyanobacteria counts peaked in the spring tide. The microbial groups driving carbon, nitrogen, sulfur and methane cycles were consistent across all spatial scales. Taxonomic groups engaged in sulfur cycling (Allochromatium, Desulfovibrio, and Thibacillus) within mangroves were abundant at all scales. Tidally-driven porewater exchange within mangroves drove a progressive increase of sulfur cycle taxonomic groups and their functional genes both temporally (tidal cycles) and spatially (from mangrove porewater to continental shelf). Overall, we revealed a unified and consistent response of microbiomes at different spatial and temporal scales to tidally-driven mangrove porewater exchange.

Are dyslexia and developmental language disorder isolated or comorbid conditions? An integrative review / Dislexia e transtorno do desenvolvimento da linguagem são quadros isolados ou comórbidos? Uma revisão integrativa

ABSTRACT Purpose: to gather scientific evidence on the linguistic skill profile in developmental dyslexia and developmental language disorder to better understand possible comorbid or isolated conditions. Methods: an integrative review of the literature. The search was conducted in SciELO, ERIC, LILACS, and PubMed. The inclusion criteria were as follows: 1) studies published and available in open-access national and international journals in full text; 2) addressing the topic in the last 10 years; 3) in English and/or Portuguese. Literature Review: the search retrieved 654 articles, the final sample comprising 10, 5 of which agreed with the hypothesis that dyslexia and developmental language disorder can be comorbid disorders, impairing reading, writing, and phonological awareness. The other studies described broader language deficits in children with developmental language disorder alone, affecting language decoding and comprehension, whereas deficits in dyslexia are more associated with phonological processing. Conclusion: there is no consensus on whether dyslexia and developmental language disorders occur simultaneously in children. However, both pose risks to reading comprehension and school performance.

RESUMO Objetivo: integrar evidências científicas sobre o perfil de habilidades linguísticas na dislexia do desenvolvimento e no transtorno do desenvolvimento da linguagem, para melhor compreensão de possíveis condições comórbidas ou quadros isolados. Métodos: trata-se de uma revisão integrativa da literatura. A busca ocorreu nas bases de dados: Scielo, Eric e LILACS, bem como no buscador PubMed. Os critérios de inclusão foram: 1) estudos publicados nos periódicos nacionais e internacionais, gratuitos, com texto completo e disponível; 2) que abordem a temática nos últimos 10 anos; 3) em inglês e/ou português. Revisão da Literatura: a busca contou com 654 artigos. A amostra final foi composta por dez artigos, nos quais cinco estudos são concordantes quanto à hipótese de que dislexia e transtorno do desenvolvimento da linguagem, podem ser transtornos comórbidos, com prejuízos na leitura, na escrita e na consciência fonológica; os demais estudos descrevem déficits mais amplos de linguagem nas crianças somente com transtorno do desenvolvimento da linguagem, implicados na decodificação e compreensão da linguagem, enquanto na dislexia os déficits estão associados ao processamento fonológico. Conclusão: não há consenso se a dislexia e o transtorno do desenvolvimento da linguagem ocorrem simultaneamente em crianças. No entanto, ambos conferem riscos à compreensão leitora e ao desempenho escolar.

Development of synthetic antigen vaccines for COVID-19.

The current pandemic called COVID-19 caused by the SARS-CoV-2 virus brought the need for the search for fast alternatives to both control and fight the SARS-CoV-2 infection. Therefore, a race for a vaccine against COVID-19 took place, and some vaccines have been approved for emergency use in several countries in a record time. Ongoing prophylactic research has sought faster, safer, and precise alternatives by redirecting knowledge of other vaccines, and/or the development of new strategies using available tools, mainly in the areas of genomics and bioinformatics. The current review highlights the development of synthetic antigen vaccines, focusing on the usage of bioinformatics tools for the selection and construction of antigens on the different vaccine constructions under development, as well as strategies to optimize vaccines for COVID-19.

Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.

The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.

Yeasts as a promising delivery platform for DNA and RNA vaccines.

Yeasts are considered a useful system for the development of vaccines for human and veterinary health. Species such as Saccharomyces cerevisiae and Pichia pastoris have been used successfully as host organisms for the production of subunit vaccines. These organisms have been also explored as vaccine vehicles enabling the delivery of antigens such as proteins and nucleic acids. The employed species possess a GRAS status (Generally Recognized as Safe) for the production of therapeutic proteins, besides promoting immunostimulation due to the properties of their wall cell composition. This strategy allows the administration of nucleic acids orally and a specific delivery to professional antigen-presenting cells (APCs). In this review, we seek to outline the development of whole yeast vaccines (WYV) carrying nucleic acids in different approaches in the medical field, as well as the immunological aspects of this vaccine strategy. The data presented here reveal the application of this platform in promoting effective immune responses in the context of prophylactic and therapeutic approaches.

Performance and serum parameters of calves (Bos taurus) subject to milk restriction associated with supplementation with 2-hydroxy-4-(methylthio)butanoic acid.

Our aim with this study was to evaluate the consumption, performance, quantitative characteristics of carcasses, biochemical profile, plasma levels of ghrelin and leptin, expression of the receptor for ghrelin (GHS-R1a) in the hypothalamus and duodenum, and the number of goblet cells in the duodenum of calves subjected to milk volume restriction and supplemented with 2-hydroxy-4-(methylthio)butanoic acid (HMTBa). We used 21 Holstein mixed-breed calves, aged between 3 and 15 d with an average weight of 36.8 kg, and housed in pens with troughs for hay, concentrate, and water. The study included two consecutive experimental periods (first period [P1] and second period [P2]) of 21 d each, with 7 d of adaptation to the diet and facilities. The calves were distributed in a completely randomized design in three treatments with seven repetitions. 1) Control: 6 liters of milk/d during P1 and 6 liters of milk/day during P2; 2) RES (milk restriction): 3 liters of milk/day during P1 and 6 liters of milk/day during P2; and 3) RES + HMTBa: 3 liters of milk/day during P1 and 6 liters of milk/day during P2 + 3.3 g of HMTBa/day in both periods. HMTBa was supplied in milk, and the amount of concentrated ration and hay provided and leftovers were recorded daily to estimate dry matter (DM) and crude protein consumption. Mean daily weight gain (DWG), final weight (FW), and feed conversion (FC) were obtained at the beginning and at the end of each 21-d period. Plasma concentrations of ghrelin and leptin, triglycerides, total protein, urea, lactate, creatinine, alkaline phosphatase, and cholesterol were measured for P1 and P2 at the end of each 21-d period. At the end of P2, animals were slaughtered; sections of the duodenum were collected to evaluate the expression of GHS-R1a and quantity of goblet cells; hypothalamus was used to evaluate the expression of GHS-R1a; rumen was used to evaluate the thickness of epithelium and keratin and the density, height, and width of ruminal papillae. In P1, total DM consumption, FW, DWG, glucose, and triglycerides were lower in the RES and RES + HMTBa groups (P < 0.001). In P2, there was an improvement in the FC of the RES + HMTBa group (compared with Control and RES groups) and a lower urea concentration in the RES group (compared with Control and RES + HMTBa groups) (P < 0.001). No differences were observed among groups regarding hormonal concentrations, histological parameters, and GHS-R1a expression in the duodenum and hypothalamus. Therefore, milk restriction combined with HMTBa supplementation promoted greater compensatory gain by a mechanism independent of changes in GHS-R1a expression and hormone levels of ghrelin and leptin.