Immunotherapy for patients with thyroid cancer: a comprehensive appraisal.

Thyroid cancer is the most common endocrine malignancy. It presents a significant challenge despite advances in treatment. Immunotherapy, which harnesses the body's immune system to fight cancer, has emerged as a potential solution. The immune system's interaction with cancer cells follows a complex process involving immune surveillance, equilibrium, and escape. On the other hand, cancer cells develop mechanisms, such as loss of antigenicity and immunogenicity, as well as creating an immunosuppressed tumor microenvironment, to evade immune response. Immunotherapy modalities, including immune checkpoint inhibitors like anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1/programmed cell death protein-ligand 1 (PD-1/PD-L1), have shown promising results in various cancers. In the context of thyroid cancer, immunotherapy, particularly PD-1/PD-L1 blockade, has been explored in patients with follicular cell-derived thyroid carcinomas and medullary thyroid carcinomas (MTCs). Clinical trials using PD-1/PD-L1 inhibitors, such as pembrolizumab and nivolumab, have been conducted for these cases, with varying degrees of success. Although preclinical studies have suggested the potential benefit of immunotherapy modalities for patients with follicular cell-derived thyroid carcinoma, to date, clinical studies have failed to demonstrate clear clinical benefits in patients with advanced thyroid cancer. Additionally, other approaches like dendritic cell vaccination and radioimmunotherapy have been explored mainly for MTC, showing potential but requiring further investigation. While immunotherapy holds promise, especially in combination with other treatments, further research, and high-quality clinical trials are necessary to establish its effectiveness in treating advanced thyroid cancers.

Immediate effects of photobiomodulation on saliva production. / Efeitos imediatos da fotobiomodulação na produção de saliva.

PURPOSE: To verify the immediate effects of photobiomodulation on the production of salivary flow and the correlation of demographic, anthropometric and medication use data. METHODS: The study included 100 healthy individuals, aged between 18 and 76 years (mean 27.2 years), randomly split into an experimental group and a placebo group. Assessments of anthropometric measurements, self-perception of saliva production and sialometry were performed. Next, LASER irradiation was carried out at an infrared wavelength (808 nanometers) with 100 milliwatts (mw) of power at five intraoral points: on the sublingual glands and bilaterally on the submandibular and parotid glands, at doses of 9, 18 and 24 joules (J). Sialometry was repeated after each application. The control group received the same procedures with placebo equipment. RESULTS: There was a statistical association in the self-perception of reduced saliva in the experimental group for the 24J dose and in sialometry and in the reduction in salivary flow for the 18J and 24J doses and an increase to 9J, in both groups. There was no association when comparing the experimental and placebo groups. Multiple multinomial regression analysis revealed that the reduction or increase in salivary flow is independent of demographic, anthropometric and medication use variables. CONCLUSION: The bioinhibitory action of photobiomodulation on healthy salivary glands occurred at a dose of 18J and 24J, while the biostimulant action happened at a dose of 9J, regardless of demographic, anthropometric variables and medication use. The self-perception of reduced salivary flow occurred at 24J.

OBJETIVO: Verificar os efeitos imediatos da fotobiomodulação na produção do fluxo salivar e a correlação dos dados demográficos, antropométricos e de uso de medicamentos. MÉTODO: Participaram do estudo 100 indivíduos saudáveis, com idade entre 18 e 76 anos (média 27,2 anos), divididos de forma randomizada em grupo experimental e grupo placebo. Foram realizadas as avaliações das medidas antropométricas, autopercepção da produção de saliva e a sialometria. Na sequência, realizou-se a irradiação do LASER no comprimento de onda infravermelho (808 nanômetros) com 100 miliwatts (mw) de potência em cinco pontos intraorais: nas glândulas sublingual e bilateralmente nas submandibulares e parótidas, nas doses 9, 18 e 24 joules (J). A sialometria foi repetida após cada aplicação. O grupo controle recebeu os mesmos procedimentos com equipamento placebo. RESULTADOS: Houve associação estatística na autopercepção de redução da saliva no grupo experimental para a dose de 24J e na sialometria e na redução do fluxo salivar para as doses 18J e 24J e aumento para 9J, em ambos os grupos. Não houve associação quando comparado entre os grupos experimental e placebo. A análise de regressão multinomial múltipla revelou que a redução ou o aumento do fluxo salivar independe das variáveis demográficas, antropométricas e uso de medicamentos. CONCLUSÃO: A ação bioinibitória da fotobiomodulação sobre as glândulas salivares saudáveis ocorreu em dose de 18J e 24J, já ação bioestimulante na dose 9J, independe das variáveis demográficas, antropométricas e uso de medicamentos. A autopercepção da redução do fluxo salivar ocorreu em 24J.

Genomic surveillance and serological profile of SARS-CoV-2 variants circulating in Macaé and nearby cities, southeastern Brazil.

Introduction: A characteristic of the COVID-19 pandemic has been the sequential emergence and global dissemination of SARS-CoV-2 variants, noted for their enhanced transmission efficiency. These variants with mutations in the Spike glycoprotein (S-glycoprotein), which interacts with ACE2 receptors in human cells is critical for infection, affects the transmissibility of the virus, which is a matter of great concern for public health. Objective: This research analyses the effects these variants on a cohort of vaccinated and naturally infected individuals from the cities of Macaé-RJ, Rio das Ostras-RJ, and Campos dos Goytacazes-RJ, Brazil, from March 2021 to March 2023. Methods: This investigation encompasses the Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2, B.1.671.3), and Omicron (BQ.1, BQ.1.1 sublines, and BF.7) variants, focusing on their genomic surveillance and implications for the disease's epidemiology. The experimental analysis included a control group (vaccinated and uninfected subjects), and an infected group (post-vaccinated subjects). Samples from nasopharyngeal swabs underwent viral detection via RT-qPCR for diagnosis confirmation. RNase H-dependent RT-qPCR (rhAmp-PCR) and third-generation sequencing were used to detect SARS-CoV-2 variants. Anti-S-glycoprotein immunoglobulins were also evaluated for vaccinated infected and noninfected volunteers. Symptoms from infected individuals were compiled in order to reveal patterns of clinical signs associated with viral infection. Results: The study included 289 participants, with infections identified by Gamma (n = 44), Delta (n = 189), and Omicron (n = 56) variants. The prevalent symptoms among the naturally infected participants were cough, fever, sore throat, headache, and runny nose. For Omicron, cognitive symptoms such as memory loss and concentration issues were reported. Interestingly, the infected vaccinated group had higher anti-S-glycoprotein IgM production (n = 28, 0.2833 ± 0.09768 OD) compared to the uninfected vaccinated group (n = 14, 0.1035 ± 0.03625 OD). Conversely, anti-S-glycoprotein IgG production was higher in the control group (n = 12, 1.770 ± 0.1393 OD) than in the infected vaccinated group (n = 26, 1.391 ± 0.1563 OD). Conclusion: This comprehensive study enables monitoring of predominant variants and their correlation with clinical cases, providing valuable insights for public health. Our research group continues to survey circulating variants, contributing to the global understanding of the pandemic.

Growth of brown trout in the wild predicted by embryo stress reaction in the laboratory.

Laboratory studies on embryos of salmonids, such as the brown trout (Salmo trutta), have been extensively used to study environmental stress and how responses vary within and between natural populations. These studies are based on the implicit assumption that early life-history traits are relevant for stress tolerance in the wild. Here we test this assumption by combining two data sets from studies on the same 60 families. These families had been experimentally produced from wild breeders to determine, in separate samples, (1) stress tolerances of singly kept embryos in the laboratory and (2) growth of juveniles during 6 months in the wild. We found that growth in the wild was well predicted by the larval size of their full sibs in the laboratory, especially if these siblings had been experimentally exposed to a pathogen. Exposure to the pathogen had not caused elevated mortality among the embryos but induced early hatching. The strength of this stress-induced change of life history was a significant predictor of juvenile growth in the wild: the stronger the response in the laboratory, the slower the growth in the wild. We conclude that embryo performance in controlled environments can be a useful predictor of juvenile performance in the wild.

Parental kinship coefficient but not paternal coloration predicts early offspring growth in lake char.

The 'good genes' hypotheses of sexual selection predict that females prefer males with strong ornaments because they are in good health and vigor and can afford the costs of the ornaments. A key assumption of this concept is that male health and vigor are useful predictors of genetic quality and hence offspring performance. We tested this prediction in wild-caught lake char (Salvelinus umbla) whose breeding coloration is known to reveal aspects of male health. We first reanalyzed results from sperm competition trials in which embryos of known parenthood had been raised singly in either a stress- or non-stress environment. Paternal coloration did not correlate with any measures of offspring performance. However, offspring growth was reduced with higher kinship coefficients between the parents. To test the robustness of these first observations, we collected a new sample of wild males and females, used their gametes in a full-factorial in vitro breeding experiment, and singly raised about 3000 embryos in either a stress- or non-stress environment (stress induced by microbes). Again, paternal coloration did not predict offspring performance, while offspring growth was reduced with higher kinship between the parents. We conclude that, in lake char, the genetic benefits of mate choice would be strongest if females could recognize and avoid genetically related males, while male breeding colors may be more relevant in intra-sexual selection.

Sex-specific effects of inbreeding in juvenile brown trout.

Inbreeding depression, that is, the reduction of health and vigour in individuals with high inbreeding coefficients, is expected to increase with environmental, social, or physiological stress. It has therefore been predicted that sexual selection and the associated stress usually lead to higher inbreeding depression in males than in females. However, sex-specific differences in life history may reverse that pattern during certain developmental stages. In some salmonids, for example, female juveniles start developing their gonads earlier than males who instead grow faster. We tested whether the sexes are differently affected by inbreeding during that time. To study the effects of inbreeding coefficients that may be typical for natural populations of brown trout (Salmo trutta), and also to control for potentially confounding maternal or paternal effects, we sampled males and females from the wild, used their gametes in a block-wise full-factorial breeding design to produce 60 full-sib families, released the offspring as yolk-sac larvae into the wild, sampled them 6 months later, identified their genetic sex, and used microsatellites to assign them to their parents. We used whole-genome resequencing to calculate the kinship coefficients for each breeding pair and hence the expected average inbreeding coefficient per family. Juvenile growth could be predicted from these expected inbreeding coefficients and the genetic sex: Females reached lower body sizes with increasing inbreeding coefficient, while no such link could be found in males. This sex-specific inbreeding depression led to the overall pattern that females were on average smaller than males by the end of their first summer.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Efeitos imediatos da fotobiomodulação na produção de saliva / Immediate effects of photobiomodulation on saliva production

RESUMO Objetivo Verificar os efeitos imediatos da fotobiomodulação na produção do fluxo salivar e a correlação dos dados demográficos, antropométricos e de uso de medicamentos. Método Participaram do estudo 100 indivíduos saudáveis, com idade entre 18 e 76 anos (média 27,2 anos), divididos de forma randomizada em grupo experimental e grupo placebo. Foram realizadas as avaliações das medidas antropométricas, autopercepção da produção de saliva e a sialometria. Na sequência, realizou-se a irradiação do LASER no comprimento de onda infravermelho (808 nanômetros) com 100 miliwatts (mw) de potência em cinco pontos intraorais: nas glândulas sublingual e bilateralmente nas submandibulares e parótidas, nas doses 9, 18 e 24 joules (J). A sialometria foi repetida após cada aplicação. O grupo controle recebeu os mesmos procedimentos com equipamento placebo. Resultados Houve associação estatística na autopercepção de redução da saliva no grupo experimental para a dose de 24J e na sialometria e na redução do fluxo salivar para as doses 18J e 24J e aumento para 9J, em ambos os grupos. Não houve associação quando comparado entre os grupos experimental e placebo. A análise de regressão multinomial múltipla revelou que a redução ou o aumento do fluxo salivar independe das variáveis demográficas, antropométricas e uso de medicamentos. Conclusão A ação bioinibitória da fotobiomodulação sobre as glândulas salivares saudáveis ocorreu em dose de 18J e 24J, já ação bioestimulante na dose 9J, independe das variáveis demográficas, antropométricas e uso de medicamentos. A autopercepção da redução do fluxo salivar ocorreu em 24J.

ABSTRACT Purpose To verify the immediate effects of photobiomodulation on the production of salivary flow and the correlation of demographic, anthropometric and medication use data. Methods The study included 100 healthy individuals, aged between 18 and 76 years (mean 27.2 years), randomly split into an experimental group and a placebo group. Assessments of anthropometric measurements, self-perception of saliva production and sialometry were performed. Next, LASER irradiation was carried out at an infrared wavelength (808 nanometers) with 100 milliwatts (mw) of power at five intraoral points: on the sublingual glands and bilaterally on the submandibular and parotid glands, at doses of 9, 18 and 24 joules (J). Sialometry was repeated after each application. The control group received the same procedures with placebo equipment. Results There was a statistical association in the self-perception of reduced saliva in the experimental group for the 24J dose and in sialometry and in the reduction in salivary flow for the 18J and 24J doses and an increase to 9J, in both groups. There was no association when comparing the experimental and placebo groups. Multiple multinomial regression analysis revealed that the reduction or increase in salivary flow is independent of demographic, anthropometric and medication use variables. Conclusion The bioinhibitory action of photobiomodulation on healthy salivary glands occurred at a dose of 18J and 24J, while the biostimulant action happened at a dose of 9J, regardless of demographic, anthropometric variables and medication use. The self-perception of reduced salivary flow occurred at 24J.

Coiling of semiflexible paramagnetic colloidal chains.

Semiflexible filaments deform into a variety of configurations that dictate different phenomena manifesting at low Reynolds number. Harnessing the elasticity of these filaments to perform transport-related processes at the microfluidic scale requires structures that can be directly manipulated to attain controllable geometric features during their deformation. The configuration of semiflexible chains assembled from paramagnetic colloids can be readily controlled upon the application of external time-varying magnetic fields. In circularly rotating magnetic fields, these chains undergo coiling dynamics in which their ends close into loops that wrap inward, analogous to the curling of long nylon filaments under shear. The coiling is promising for the precise loading and targeted transport of small materials, however effective implementation requires an understanding of the role that field parameters and chain properties play on the coiling features. Here, we investigate the formation of coils in semiflexible paramagnetic chains using numerical simulations. We demonstrate that the size and shape of the initial coils are governed by the Mason and elastoviscous numbers, related to the field parameters and the chain bending stiffness. The size of the initial coil follows a nonmonotonic behavior with Mason number from which two regions are identified: (1) an elasticity-dependent nonlinear regime in which the coil size decreases with increasing field strength and for which loop shape tends to be circular, and (2) an elasticity-independent linear regime where the size increases with field strength and the shape become more elliptical. From the time scales associated to these regimes, we identify distinct coiling mechanisms for each case that relate the coiling dynamics to two other configurational dynamics of paramagnetic chains: wagging and folding behaviors.

Efeitos do treinamento resistido sobre indicadores de saúde de sobreviventes de câncer de mama / Effects of resistance training on health indicators in breast cancer survivors

O objetivo deste estudo foi investigar os efeitos do treinamento resistido sobre indicadores de saúde em sobreviventes de câncer de mama. Vinte e duas mulheres com histórico de mastectomia e linfadenectomia completaram 12 semanas de treinamento. Avaliações de força, índice de massa corporal, composição corporal, aspectos hematológicos, bioquímicos e de estabilidade de membrana eritrocitária foram realizadas antes e depois do período de treinamento. Em todos os exercícios, ocorreram ganhos significantes de força máxima e resistência de força. Além disso, houve diminuição do percentual de gordura corporal, aumento do percentual de massa magra, redução de eritrócitos, plaquetas e hemoglobina, bem como mudanças desejáveis para todas as variáveis de perfil lipídico. Em conjunto, esses achados destacam o impacto multidimensional do treinamento resistido sobre a saúde de sobreviventes de câncer de mama e revelam a necessidade de monitoramento constante desse público.

The present study aimed to investigate the effects of resistance training on health indicators in breast cancer survivors. Twenty-two women with a history of mastectomy and lymphadenectomy completed 12 weeks of training. Strength, body mass index, body composition, hematological, and biochemical aspects, and erythrocyte membrane stability were performed before and after the training. In all exercises, there were significant gains in maximal force and force endurance. Moreover, there was a decrease in body fat percentage, an increase in lean mass percentage, a reduction in erythrocytes, platelets, and hemoglobin, as well as desirable changes for all lipid profile variables. Altogether, these findings highlight the multidimensional impact of resistance training on the health of breast cancer survivors and reveal the need for constant monitoring of this public.

Comprehensive expression analyses of the ABCG subfamily reveal SvABCG17 as a potential transporter of lignin monomers in the model C4 grass Setaria viridis.

Although several aspects of lignin metabolism have been extensively characterized, the mechanism(s) by which lignin monomers are transported across the plasma membrane remains largely unknown. Biochemical, proteomic, expression and co-expression analyses from several plant species support the involvement of active transporters, mainly those belonging to the ABC superfamily. Here, we report on the genome-wide characterization of the ABCG gene subfamily in the model C4 grass Setaria viridis and further identification of the members potentially involved in monolignol transport. A total of 48 genes encoding SvABCGs were found in the S. viridis genome, from which 21 SvABCGs were classified as full-size transporters and 27 as half-size transporters. Comprehensive analysis of the ABCG subfamily in S. viridis based on expression and co-expression analyses support a role for SvABCG17 in monolignol transport: (i) SvABCG17 is orthologous to AtABCG29, a monolignol transporter in Arabidopsis thaliana; (ii) SvABCG17 displays a similar expression profile to that of lignin biosynthetic genes in a set of different S. viridis tissues and along the elongating internode; (iii) SvABCG17 is highly co-expressed with lignin-related genes in a public transcriptomic database; (iv) SvABCG17displays particularly high expression in the top of the S. viridis elongating internode, a tissue undergoing active lignification; (v) SvABCG17 mRNA localization coincides with the histochemical pattern of lignin deposition; and (vi) the promoter of SvABCG17 is activated by secondary cell wall-associated transcription factors, especially by lignin-specific activators of the MYB family. Further studies might reveal further aspects of this potential monolignol transporter, including its real substrate specificity and whether it works redundantly with other ABC members during S. viridis lignification.

Investigating population-level immunosenescence: From bench to bedside.

The immune response is remodeled with aging in a process called immunosenescence. Some immunologists conceive immunosenescence as an adaptation of immunity to the aged immune-environment rather than a merely collapsed reactivity of immune cells against microbes and tumor cells. Others believe on an uninterrupted activation of the innate immune system with aging, leading to a low grade, sterile and chronic proinflammatory state called inflammaging. For instance, it is possible that chronic infection by cytomegalovirus leads to persistent production of viral load. This phenomenon offers periodic stimuli to the immune system that ultimately contribute to the remodeling of the immune response. If investigating immunosenescence at the cellular level is already a difficult task, considering the population level is much more complex. However, by studying immunosenescence at the population level, we can extract valuable results with viable applications. While studies with animal models allow scientists to deepen their understanding of the mechanisms of immunosenescence, studying large populations can bring practical innovations to medicine and the health system. Many researchers and funders have dedicated themselves to producing methods for the evaluation of immunosenescence on a large scale, aiming to elucidate new mechanisms by which diseases are established in the elderly. The description of how the immune response is remodeled with aging emerges as a new tool to identify the subset of subjects in which unhealthy aging is a matter of time, to help better individualize clinical management and select patients who may benefit. of early interventions. This review focuses on functional assays as valuable methods for measuring the remodeling of the immune response with aging and discuss their clinical impact. We also recall fundamental concepts for understanding the aging process of the immune response. In addition, we highlight future prospects for immunosenescence research.

Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.

Influence of SARS-CoV-2 inactivation by different chemical reagents on the humoral response evaluated in a murine model.

Viral inactivation for antibody induction purposes, among other applications, should ensure biosafety, completely avoiding the risk of infectivity, and preserving viral immunogenicity. ß-propiolactone (BPL) is one of the most used reagents for viral inactivation, despite its high toxicity and recent difficulties related to importation, experienced in Brazil during the SARS-CoV-2 pandemic. In this context, the main objectives of this work were to test different inactivation procedures for SARS-CoV-2 and to evaluate the induction of neutralizing antibodies in mice immunized with antigenic preparations obtained after viral treatment with formaldehyde (FDE), glutaraldehyde (GDE), peroxide hydrogen (H2O2), as well as with viral proteins extract (VPE), in parallel with BPL. Verification of viral inactivation was performed by subsequent incubations of the inactivated virus in Vero cells, followed by cytopathic effect and lysis plaques observation, as well as by quantification of RNA load using reverse transcription-quantitative real time polymerase chain reaction. Once viral inactivation was confirmed, cell culture supernatants were concentrated and purified. In addition, an aliquot inactivated by BPL was also subjected to viral protein extraction (VPE). The different antigens were prepared using a previously developed microemulsion as adjuvant, and were administered in a four-dose immunization protocol. Antibody production was comparatively evaluated by ELISA and Plaque Reduction Neutralization Tests (PRNT). All immunogens evaluated showed some level of IgG anti-SARS-CoV-2 antibodies in the ELISA assay, with the highest levels presented by the group immunized with FDE-inactivated viral antigen. In the PRNT results, except for VPE-antigen, all other immunogens evaluated induced some level of neutralizing anti-SARS-CoV-2 antibodies, and the FDE-antigen stood out again with the most expressive values. Taken together, the present work shows that FDE can be an efficient and affordable alternative to BPL for the production of inactivated SARS-CoV-2 viral antigen.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis.

Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Translating the immune microenvironment of thyroid cancer into clinical practice.

Thyroid cancer is an excellent model for studying tumor immune microenvironment, as it often shows local signs of an immune response. The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. The final composition of this cellular aggregate is associated with the clinical aggressiveness characteristics of the neoplasm. High-performance multiplex technologies suggest that specific genetic signatures of the tumor immune microenvironment may provide data for the delineation of a robust prognostic model. Several proposals integrate clinic, pathologic and immunological information in an attempt to translate the knowledge gained from molecular science into a more personalized approach for the treatment strategy of patients with thyroid cancer. In addition, the tumor immune microenvironment displays multiple molecular connections between cells, revealing complex crosstalk. This interesting network generates several molecular nodes that can be used as targets for immunotherapy. In this scenario, immunotherapy emerges as a promising weapon, mainly for patients with advanced thyroid cancer, both medullary and follicular cell-derived. In fact, although most patients with thyroid cancer have an excellent prognosis with current therapies, around 30% of cases evolve in an unfavorable way, leading to the urgent need to improve immunotherapy for high-risk patients. Preclinical and early clinical investigations are providing optimistic prospects, but more studies are needed to make immunotherapy a more viable and efficient tool for years to come.

Periodic deformation of semiflexible colloidal chains in eccentric time-varying magnetic fields.

Elastic filaments driven out of equilibrium display complex phenomena that involve periodic changes in their shape. Here, the periodic deformation dynamics of semiflexible colloidal chains in an eccentric magnetic field are presented. This field changes both its magnitude and direction with time, leading to novel nonequilibrium chain structures. Deformation into S-, Z-, and 4-mode shapes arises via the propagation and growth of bending waves. Transitions between these morphologies are governed by an interplay among magnetic, viscous, and elastic forces. Furthermore, the periodic behavior leading to these structures is described by four distinct stages of motion that include rotation, arrest, bending, and stretching of the chain. These stages correspond to specific intervals of the eccentric field's period. A scaling analysis that considers the relative ratio of viscous to magnetic torques via a critical frequency illustrates how to maximize the bending energy. These results provide new insights into controlling colloidal assemblies by applying complex magnetic fields.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Fim dos benefícios fiscais aos agrotóxicos, sustentabilidade da agricultura e a saúde no Brasil / End of tax benefits for pesticides, agricultural sustainability and health in Brazil

RESUMO O presente artigo avaliou o fim dos benefícios fiscais dados aos agrotóxicos a partir dos microdados do Censo agropecuário de 2017. Realizou-se um estudo descritivo explorando duas variáveis pesquisadas: a despesa com agrotóxicos e o lucro obtido com a atividade agropecuária. Foram traçados cenários de aplicação de alíquotas de tributação dos agrotóxicos e os seus respectivos aumentos de preços, o que possibilitou avaliar os impactos diretos na lucratividade dos produtores. O cenário de tributação que gere um aumento de 15% nos preços dos agrotóxicos reduziria a lucratividade em cerca de 5,1% em 2017 (R$ 4,8 bilhões). Contudo, os maiores impactados seriam os produtores de commodities, com uma redução média de 9,6% na lucratividade. Discutiram-se esses resultados à luz de dois prismas: o impacto na renda do produtor e possíveis consequências no aumento de preços da cesta básica; e a capacidade da função extrafiscal do imposto em regular o uso dos agrotóxicos e redirecionar possíveis mudanças na tomada de decisão sobre os métodos de controle de pragas mais sustentáveis. Concluiu-se que há necessidade de harmonizar regras fiscais à uma política pública mais equilibrada no âmbito do setor agropecuário que garantisse a defesa da saúde da população e a sustentabilidade ambiental.

ABSTRACT This paper assesses the end of the tax incentives given to pesticides, based on the constitutionality analysis lawsuit (ADI 5553) that will be judged by the Supreme Court, which discusses the exemptions of ICMS and IPI on these products. Based on the last Brazilian Census Survey we evaluate the tax incidence of ICMS and IPI on agricultural expenditure and profitability of the agricultural establishment in some diferent scenarios. A 15% increase in pesticide prices would have an impact on costs and profitability of approximately R$ 4 and R$ 6.8 billion (-7%), respectively. This represents a value of almost R$ 10 billion less than calculated by a similar study released by the Sindicato Nacional da Indústria da Defesa Vegetal (Sindiveg) for a scenario of equivalent price increase. We discussed not only the impact results in income of the producer, but also the capacity of the extrafiscal function of the tax to regulate the use of pesticides and redirect possible changes in decision making on pest control methods, enabling the transition to a more sustainable and healthy agriculture. Finally, we conclude that, regardless of the outcome of the judgment of ADI 5553, the problem of negative externalities resulting from the use of pesticides does not end with the end of fiscal incentives to them, as they depend on the formulation of a more balanced public policy within the scope of the agricultural sector that would guarantee the defense of the population's health and environmental sustainability.

The Participation of a Malignant Catarrhal Fever Virus and Mycoplasma bovis in the Development of Single and Mixed Infections in Beef and Dairy Cattle With Bovine Respiratory Disease.

The bovine respiratory disease (BRD) complex is a multietiological and multifactorial disease associated with a wide range of viral and bacterial pathogens. This study evaluated the contribution of specific infectious disease agents in the development of BRD in cattle from Brazil and determined if a virus within the malignant catarrhal fever virus (MCFV) group and Mycoplasma bovis, acting individually or in conjunction, can be associated with the development of BRD. Formalin-fixed paraffin-embedded pulmonary sections were used in immunohistochemical assays to determine the intralesional presence of six antigens associated with BRD: bovine alphaherpesvirus 1 (BoHV-1), bovine parainfluenza virus 3 (BPIV-3), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), MCFV, and M. bovis. Pneumonia was diagnosed in 82.7% (120/145) of all cattle evaluated. Interstitial pneumonia (60%, 72/120) and suppurative bronchopneumonia (25.8%, 31/120) were the most frequent patterns of pneumonia identified. Intralesional antigens of MCFV (53.3%, 64/120) were the most frequently associated with BRD, followed by M. bovis (47.5%, 57/120), BVDV (42.5%, 51/120), BoHV-1 (28.3%, 34/120), BRSV (24.2%, 29/120), and BPIV-3 (8.3%, 10/120). Additionally, antigens of BVDV, MCFV, and M. bovis were the most frequently identified agents associated with singular and concomitant infections. The MCFV identified during this study is more likely to be ovine gammaherpesvirus 2 (OvHV-2), since OvHV-2 is the only MCFV identified within the geographical region of this study. Interstitial pneumonia with proliferative vascular lesions may be a useful histologic feature to differentiate MCFV-induced pneumonia from other viral pneumonias of cattle. These results demonstrate that MCFV and M. bovis, in single or mixed infections, can produce pneumonia in cattle and should therefore be considered as primary agents in the development of BRD.