On the genetic basis of tail-loss evolution in humans and apes.

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

Charcot Arthropathy of the Shoulder Associated with Syringomyelia: A Report of 2 Cases / Artropatia do ombro de Charcot associada à Siringomielia: Relato de 2 casos

Charcot arthropathy of the shoulder caused by syringomyelia is a unusual degenerative disorder, frequently misdiagnosed and with few cases described in the literature. The diagnosis is made by clinical evaluation and radiological examinations with radiography and magnetic resonance imaging. However, the correct diagnosis and treatment is possible by carefully medical evaluation and can improve patient symptoms. Therefore, this study aimed to report two cases of Charcot arthropathy caused by syringomyelia. After achieving correct neurosurgical evaluation and magnetic resonance imaging, the diagnosis was made. The first case is a 53-year-old man with a click on his right shoulder for at least 12 months, associated with local edema, pain and limitation of joint range of motion. The second is a 45-year-old man with pain in the right upper limb and difficulty moving the joint for at least 24 months, associated with progressive worsening of the collection and edema in the ipsilateral upper limb. Posterior fossa decompression was performed, with symptoms relief after surgery. Posterior fossa decompression is a treatment that seems to be effective in reducing symptoms, especially when the diagnosis is early. However, this type of treatment still remains controversial, requiring further studies.

A artopatia de Charcot do ombro causada por siringomielia é uma doença degenerativa incomum, frequentemente subdiagnosticada e com poucos casos descritos na literatura. O diagnóstico é feito pela avaliação clínica e exames radiológicos com radiografia e ressonância magnética. No entanto, o diagnóstico e tratamento corretos são possíveis mediante avaliação médica criteriosa e podem melhorar os sintomas do paciente. Portanto, este trabalho objetiva relatar dois casos de artropatia de Charcot causada por siringomielia. Após obter correta avaliação neurocirúrgica e ressonância magnética, o diagnóstico foi feito. O primeiro caso é um homem de 53 anos com clique no ombro direito por pelo menos 12 meses, associado a edema local, dor e limitação da amplitude do movimento articular. O segundo é um homem de 45 anos com dor em membro superior direito e dificuldade de movimentação articular há pelo menos 24 meses, associada a piora progressiva da coleção e edema em membro superior ipsilateral. A descompressão da fossa posterior foi realizada, com alívio dos sintomas após a cirurgia. A descompressão da fossa posterior é um tratamento que parece eficaz na redução dos sintomas, principalmente quando o diagnóstico é precoce. Porém, esse tipo de tratamento ainda permanece controverso, necessitando de mais estudos.

Cervical cancer screening in Brazilian Amazon Indigenous women: Towards the intensification of public policies for prevention.

BACKGROUND: Indigenous women are vulnerable to cervical cancer. Screening is a strategy to reduce the burden of the disease. OBJECTIVE: To evaluate the prevalence profile of cervical cancer screening cytological results in Brazilian indigenous women by age and frequency of tests compared to non-indigenous women. METHODS: A cross-sectional study evaluating the prevalences of screening test results in indigenous women assisted in the Brazilian Amazon from 2007 to 2019 (3,231 tests), compared to non-indigenous women (698,415 tests). The main outcome was the cytological result. Other variables were frequency, age groups, and population. The frequency was categorized as "1st test", the first test performed by the women in their lifetime, or "screening test," tests from women who had previously participated in screening. Analyzes were based on prevalences by age group and population. We used Prevalence Ratios (PR) and 95% Confidence Intervals for risks and linear regression for trends. RESULTS: Data from the 1st test showed a higher prevalence of Low-grade Squamous Intraepithelial Lesion (LSIL) in indigenous women. Peaks were observed in indigenous under 25, 35 to 39, 45 to 49, and 60 to 64. The prevalence of High-grade Squamous Intraepithelial Lesion or more severe (HSIL+) was low in both groups in women younger than 25. The indigenous HSIL+ prevalence curve showed a rapid increase, reaching peaks in women from 25 to 34 years, following a slight decrease and a plateau. In screening tests, HSIL+ was more prevalent in indigenous from 25 to 39 (PR 4.0,2.3;6.8) and 40 to 64 (PR 3.8,1.6;9.0). In indigenous, the PR of HSIL+ results in screening tests over 1st tests showed no screening effect in all age groups. In non-indigenous, there was a significant effect toward protection in the age groups over 25. CONCLUSION: This screening study of indigenous women from diverse ethnicities showed a higher prevalence of cytological LSIL and HSIl+ than in non-indigenous women. The protective screening effect in reducing HSIL+ prevalence was not observed in indigenous.

Implicações no cuidado de um familiar doente: mulheres negras cuidadoras

Introdução: As desvantagens ligadas ao gênero feminino são visualizadas em diversos aspectos da vida, mediante ao patriarcado. É possível compreender que, no caso de mulheres negras, estas se encontram desfavorecidas frente as estruturas sociais, atravessadas por condicionantes de classe, raça e gênero. Além disso, é visto que, em diversos casos, as cuidadoras mulheres, sobretudo, mulheres negras, não escolhem de forma voluntária este papel dentro da conjuntura familiar. Objetivo: Identificar as implicações do cuidado ao familiar adoecido realizado por mulheres negras cuidadoras considerando suas condições socioculturais. Metodologia: Este trabalho é uma revisão integrativa, cuja busca no banco de dados foi realizada em dezembro de 2020, onde 3 resultados foram encontrados na base de dados Web of Science, 48 na base de dados PubMed e 29 na base de dados LILACS. Depois de ler os resumos dos 80 artigos e aplicar os critérios de exclusão, 7 artigos foram selecionados para leitura completa. Finalmente, 4 artigos foram incluídos para análise. Resultados: Apenas um estudo abordou exclusivamente mulheres, e a maioria eram afro-americanos. Dados indicam que, dentro de uma comunidade quilombola, o cuidado com a saúde é repassado do mais velho para o mais novo, como símbolo de respeito aos saberes ancestrais. Além disso, ficou evidente que cuidadores afro-americanos de pessoas com demência precisam de informações de qualidade sobre cuidados e autocuidado, necessitando de recursos em sua comunidade. Conclusão: É possível notar as desigualdades de acordo com as construções históricas, políticas e culturais causadas, para diferenciar homens e mulheres no cuidado familiar. Havendo uma necessidade de debates que tenham como enfoque a população negra, principalmente as cuidadoras, visando estratégias para reduzir sua sobrecarga para cuidar de familiares em adoecimento.

Introducción: Las desventajas vinculadas al género femenino se visualizan en diversos aspectos de la vida, a través del patriarcado. Es posible entender que, en el caso de las mujeres negras, ellas están en desventaja frente a las estructuras sociales, atravesadas por condiciones de clase, raza y género. Además, se observa que, en varios casos, las cuidadoras, especialmente las mujeres negras, no eligen voluntariamente este rol dentro del contexto familiar. Objetivo: Identificar las implicaciones del cuidado a un familiar enfermo realizado por cuidadoras negras considerando sus condiciones socioculturales. Metodología: Este trabajo es una revisión integradora, cuya búsqueda en la base de datos tuvo lugar en diciembre de 2020, donde se encontraron 3 resultados en la base de datos Web of Science, 48 en la base de datos PubMed y 29 en la base de datos LILACS. Después de leer los resúmenes de los 80 artículos. y aplicar los criterios de exclusión, se seleccionaron 7 artículos para su lectura íntegra. Finalmente, 4 artículos fueron incluidos para el análisis. Resultados: Solo un estudio se refería exclusivamente a mujeres, y la mayoría eran afroamericanas. Los datos indican que, en el seno de una comunidad quilombola, los cuidados de salud se transmiten de los más ancianos a los más jóvenes, como símbolo de respeto a los conocimientos ancestrales. Además, se puso de manifiesto que los cuidadores afroamericanos de personas con demencia necesitan información de calidad sobre cuidados y autocuidados y precisan recursos en su comunidad. Conclusión: Es posible percibir las desigualdades según las construcciones históricas, políticas y culturales provocadas, para diferenciar hombres y mujeres en el cuidado de la familia. Hay una necesidad de debates que se centren en la población negra, especialmente en las cuidadoras, con miras a elaborar estrategias para reducir su carga para cuidar a los familiares enfermos.

Introduction: The disadvantages linked to the female gender are viewed in different aspects of life, through patriarchy. It is possible to understand that, in the case of black women, they are disadvantaged in the face of social structures, crossed by class, race and gender conditioning factors. In addition, it is seen that, in several cases, female caregivers, especially black women, do not voluntarily choose this role within the family environment. Objective: To identify the implications of care for a sick family member performed by black women caregivers considering their sociocultural conditions. Methodology: This work is an integrative review, whose search in the database was carried out in December 2020, where 3 results were found in the Web of Science database, 48 in the PubMed database and 29 in the LILACS database. After reading the abstracts of the 80 articles and applying the exclusion criteria, 7 articles were selected for full reading. Finally, 4 articles were included for analysis. Results: Only one study exclusively addressed women, and most were African Americans. Data indicate that, within a quilombola community, health care is passed on from the oldest to the youngest, as a symbol of respect for ancestral knowledge. In addition, it became evident that African-American caregivers of people with dementia need quality information about care and self-care, requiring resources in their community. Conclusion: It is possible to notice the inequalities according to the historical, political and cultural constructions caused, in order to differentiate men and women in family care. There is a need for debates that focus on the black population, especially caregivers, aiming at strategies to reduce their burden to care for sick family members.

Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study.

BACKGROUND: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. METHODS: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. FINDINGS: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6-33 days after the first dose and 5-40 days after the second dose. Mpox-convalescent samples were collected 20-102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20-102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. INTERPRETATION: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. FUNDING: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.

Boophilin D1, a Kunitz type protease inhibitor, as a source of inhibitors for the ZIKA virus NS2B-NS3 protease.

Arboviruses are a global concern for a multitude of reasons, including their increased incidence and human mortality. Vectors associated with arboviruses include the mosquito Aedes sp., which is responsible for transmitting the Zika virus. Flaviviruses, like the Zika virus, present only one chymotrypsin-like serine protease (NS3) in their genome. Together with host enzymes, the NS2B co-factor NS3 protease complex are essential for the viral replication cycle by virus polyprotein processing. To search for Zika virus NS2B-NS3 protease (ZIKVPro) inhibitors, a phage display library was constructed using the Boophilin domain 1 (BoophD1), a thrombin inhibitor from the Kunitz family. A BoophilinD1 library mutated at positions P1-P4' was constructed, presenting a titer of 2.9x106 (cfu), and screened utilizing purified ZIKVPro. The results demonstrated at the P1-P4' positions the occurrence of 47% RALHA sequence (mut 12) and 11.8% RASWA sequence (mut14), SMRPT, or KALIP (wt) sequence. BoophD1-wt and mutants 12 and 14 were expressed and purified. The purified BoophD1 wt, mut 12 and 14, presented Ki values for ZIKVPro of 0.103, 0.116, and 0.101 µM, respectively. The BoophD1 mutant inhibitors inhibit the Dengue virus 2 protease (DENV2) with Ki values of 0.298, 0.271, and 0.379 µM, respectively. In conclusion, BoophD1 mut 12 and 14 selected for ZIKVPro demonstrated inhibitory activity like BoophD1-wt, suggesting that these are the strongest Zika inhibitors present in the BoophD1 mutated phage display library. Furthermore, BoophD1 mutants selected for ZIKVPro inhibit both Zika and Dengue 2 proteases making them potential pan-flavivirus inhibitors.

Clinical management of salivary gland hypofunction in patients with head and neck cancer: a scoping review of physical salivary stimulation methods.

OBJECTIVE(S): This scoping review aims to map the scientific literature on the therapies currently available for physical salivary stimulation in individuals with hyposalivation caused by radiotherapy. STUDY DESIGN: Studies were included when they comprised the target population of adult individuals receiving radiotherapy of the head and neck region and who developed or were at risk of developing hyposalivation. Two reviewers selected the studies and extracted data on the type of physical salivary stimulation therapy used, the degree of glandular tissue involvement, and the percentage of salivary flow alteration. Therapies were classified according to either prophylactic application (before/during radiotherapy) or therapeutic application (post-radiotherapy). RESULTS: Sixteen articles were included: 4 tested transcutaneous electrical nerve stimulation (TENS), 3 studied low-level lasers, 7 researched acupunctures, and 2 investigated acupuncture-like TENS. The outcomes of the prophylactic studies indicated beneficial effects (similar salivary flow or reduced salivary flow loss), although most studies did not include a comparable control group. Therapeutic studies presented conflicting results. CONCLUSION(S): Prophylactic therapies of physical salivary stimulation may produce better effects than therapeutic applications. However, the protocols best indicated could not be defined. Well-designed, controlled clinical trials should be researched in the future to support the clinical recommendation of any of these treatments.

Mpox vaccine and infection-driven human immune signatures.

Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS' immunogenicity and inform vaccine administration and design. Methods: We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings: Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation: JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells. Funding: Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.

A proteomics-MM/PBSA dual approach for the analysis of SARS-CoV-2 main protease substrate peptide specificity.

The main protease Mpro of SARS-CoV-2 is a well-studied major drug target. Additionally, it has been linked to this virus' pathogenicity, possibly through off-target effects. It is also an interesting diagnostic target. To obtain more data on possible substrates as well as to assess the enzyme's primary specificity a two-step approach was introduced. First, Terminal Amine Isobaric Labeling of Substrates (TAILS) was employed to identify novel Mpro cleavage sites in a mouse lung proteome library. In a second step, using a structural homology model, the MM/PBSA variant MM/GBSA (Molecular Mechanics Poisson-Boltzmann/Generalized Born Surface Area) free binding energy calculations were carried out to determine relevant interacting amino acids. As a result, 58 unique cleavage sites were detected, including six that displayed glutamine at the P1 position. Furthermore, modeling results indicated that Mpro has a far higher potential promiscuity towards substrates than expected. The combination of proteomics and MM/PBSA modeling analysis can thus be useful for elucidating the specificity of Mpro, and thus open novel perspectives for the development of future peptidomimetic drugs against COVID-19, as well as diagnostic tools.

Information sources of Brazilian undergraduate dental students during the COVID-19 outbreak: a cross-sectional study

Aim: This cross-sectional study aimed to investigate where Brazilian dental students seek information about COVID-19 by a self-administered web-based questionnaire. Methods: A social network campaign on Instagram was raised to approach the target population. The dental students responded to a multiple-response question asking where or with whom they get information about COVID-19. The possible answers were government official websites or health and education institutions websites, TV Programs, professors, social media, scientific articles, health professionals, and family members. The data were analyzed by descriptive statistics, and the frequency distributions of responses were evaluated by gender, age, type of institution, and year of enrollment. Results: A total of 833 valid responses were received. The main source of information used by the dental students were government official websites or health and education institutions websites, which were reported by 739 (88.7%) participants. In the sequence, 477 (57.3%) participants chose health professionals while 468 (56.2%) chose scientific articles as information sources. The use of social media was reported by 451 (54.1%) students, while TV programs were information sources used by 332 (39.9%) students. The least used information sources were professors, reported by 317 (38.1%) students, and family members, chosen only by 65 (7.8%) participants. Conclusion: Brazilian dental students rely on multiple information sources to stay informed about COVID-19, mainly focusing their information-seeking behavior on governmental and health professional's websites

Semysinthetic biflavonoid Morelloflavone-7,4',7″,3‴,4‴-penta-O-butanoyl is a more potent inhibitor of Proprotein Convertases Subtilisin/Kexin PC1/3 than Kex2 and Furin.

BACKGROUND: Garcinia brasiliensis is a species native to the Amazon forest. The white mucilaginous pulp is used in folk medicine as a wound healing agent and for peptic ulcer, urinary, and tumor disease treatments. The activity of the proprotein convertases (PCs) Subtilisin/Kex is associated with the development of viral, bacterial and fungal infections, osteoporosis, hyperglycemia, atherosclerosis, cardiovascular, neurodegenerative and neoplastic diseases. METHODS: Morelloflavone (BF1) and semisynthetic biflavonoid (BF2, 3 and 4) from Garcinia brasiliensis were tested as inhibitor of PCs Kex2, PC1/3 and Furin, and determined IC50, Ki, human proinflammatory cytokines secretion in Caco-2 cells, mechanism of inhibition, and performed molecular docking studies. RESULTS: Biflavonoids were more effective in the inhibition of neuroendocrine PC1/3 than mammalian Furin and fungal Kex2. BF1 presented a mixed inhibition mechanism for Kex2 and PC1, and competitive inhibition for Furin. BF4 has no good interaction with Kex2 and Furin since carboxypropyl groups results in steric hindrance to ligand-protein interactions. Carboxypropyl groups of BF4 promote steric hindrance with Kex2 and Furin, but effective in the affinity of PC1/3. BF4 was more efficient at inhibiting PCl/3 (IC50 = 1.13 µM and Ki = 0,59 µM, simple linear competitive mechanism of inhibition) than Kex2, Furin. Also, our results strongly suggested that BF4 also inhibits the endogenous cellular PC1/3 activity in Caco-2 cells, since PC1/3 inhibition by BF4 causes a large increase in IL-8 and IL-1ß secretion in Caco-2 cells. CONCLUSIONS: BF4 is a potent and selective inhibitor of PC1/3. GENERAL SIGNIFICANCE: BF4 is the best candidate for further clinical studies on inhibition of PC1/3.

Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats.

We investigated the role of angiotensin II type 1 (AT1 receptor) and type 2 (AT2 receptor) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by acute restraint stress in male rats. For this, rats received bilateral microinjection of either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319, the selective MAS receptor antagonist A-779, or vehicle 10 min before a 60 min restraint session. Then, behavior in the FST was evaluated immediately after the restraint (15 min session) and 24 h later (5 min session). The behavior in the FST of a non-stressed group was also evaluated. We observed that acute restraint stress decreased immobility during both sessions of the FST in animals treated with vehicle in the MeA. The decreased immobility during the first session was inhibited by intra-MeA administration of PD123319, whereas the effect during the second session was not identified in animals treated with A-779 into the MeA. Microinjection of PD123319 into the MeA also affected the pattern of active behaviors (i.e., swimming and climbing) during the second session of the FST. Taken together, these results indicate an involvement of angiotensinergic neurotransmissions within the MeA in behavioral changes in the FST evoked by stress.

Implementación de la Estrategia Madre-Hijo São-Borjense: investigación-acción / Implementação da Estratégia Mãe-Bebê São-Borjense: pesquisa-ação / Implementation of the São-Borjense Mother-Baby Strategy: Action research

Objective: To describe the process of conception and implementation of the São-Borjense Mother- Baby Strategy. Materials and method: This is an action research study developed between March 2018 and October 2019, from a simple random sampling resulting in the participation of 5 managers, 27 health professionals, and 23 pregnant women from the maternal and child health care network in the municipality of São Borja, Rio Grande do Sul, Brazil. The participants of the focus groups guided the identification and survey of data; thematic content analysis was used to categorize data. Results: Based on a systematic and collaborative plan of intervention the following path was defined: i) conception of the Strategy and agreements with local managers; ii) sensitization of the actors and identification of demands, through focus groups with managers, professionals and health care users; and iii) implementation of actions of the São-Borjense Mother-Baby Strategy. Conclusions: Based on the course taken from the conception to the implementation of the Strategy, we conclude that leading innovative processes and transposing traditional models of intervention is possible through interaction, sharing and translation of knowledge and practices among academy, agents, managers, professionals and health care users.

Objetivo: describir el proceso de concepción e implementación de la Estrategia Madre-Hijo São-Borjense. Materiales y método: estudio de investigación-acción, desarrollado entre marzo de 2018 y octubre de 2019, a partir de un muestreo aleatorio simple que contó con la participación de 5 gestores, 27 profesionales de la salud y 23 mujeres embarazadas de la red de atención de salud materno infantil en el municipio de São Borja, Rio Grande do Sul, Brasil. La técnica de grupo focal fue empleada para la identificación y recolección de datos, mientras que el análisis de contenido temático permitió la categorización de estos. Resultados: a partir de un plan sistematizado y colaborativo de intervenciones, fue posible definir la siguiente ruta de trabajo: i) concepción de la Estrategia y acuerdos con gestores locales; ii) sensibilización de los actores e identificación de demandas a través de grupos focales con gestores, profesionales y usuarios de la salud; iii) implementación de acciones de la Estrategia Madre-Hijo São-Borjense. Conclusiones: con base en la ruta tomada desde la concepción hasta la implementación de la Estrategia, concluimos que liderar procesos innovadores y transponer modelos tradicionales de intervención es posible a través de la interacción, el intercambio y la traducción de conocimientos y prácticas entre agentes, academia, gestores, profesionales y usuarios de la salud.

Objetivo: descrever o processo de concepção e implementação da Estratégia Mãe-Bebê São-Borjense. Materiais e método: trata-se de uma pesquisa-ação, desenvolvida entre março de 2018 e outubro de 2019, a partir de uma amostragem aleatória simples que contou com a participação de 5 gestores, 27 profissionais da saúde e 23 gestantes da rede de atenção à saúde materno-infantil do município de São Borja, Rio Grande do Sul, Brasil. O grupo focal guiou a identificação e o levantamento dos dados, e a análise de conteúdo temática permitiu a categorização dos dados. Resultados: a partir de um plano sistematizado e colaborativo de intervenções, foi possível o seguinte percurso: i) concepção da Estratégia e acordos com gestores locais; ii) sensibilização dos atores e identificação de demandas, por meio de grupos focais com gestores, profissionais e usuários da saúde; iii) implementação de ações da Estratégia Mãe-Bebê São-Borjense. Conclusões: com base no percurso transcorrido da concepção à implementação da Estratégia, conclui-se que protagonizar processos inovadores e transpor modelos tradicionais de intervenção é possível pela interação, pelo compartilhamento e pela tradução de conhecimentos e práticas entre agentes, academia, gestores, profissionais e usuários da saúde.

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.

Intervenções realizadas com cuidadores de adultos com condições crônicas em atençío domiciliar: revisío integrativa / Interventions carried out to adult's caregivers with chronic conditions in home care: integrative review / Intervenciones realizadas en los cuidadores de adultos com condiciones crónicas em el cuidado domiciliario: revisión integradora

OBJETIVO: Identificar e caracterizar as intervenções realizadas com cuidadores de adultos com condições crônicas assistidos pela atenção domiciliar. METODOLOGIA: Revisão integrativa cuja busca nas bases foi realizada em março de 2021 e foram encontrados 1.573 resultados na base Web of Science, 633 na PubMed e um na base Lilacs. Foi seguido os seis passos da revisão integrativa. Após a leitura dos resumos e aplicados os critérios de exclusão, 229 artigos foram selecionados para leitura na íntegra. Após essa etapa resultou em 39 artigos, os quais compuseram o escopo de análise deste estudo. Foram inclusos estudos em inglês, espanhol e português. Foi realizada a análise descritiva e a análise de conteúdo. RESULTADOS: As três formas de intervenção ­ psicoeducacional, psicoterapêutica ou psicossocial ­ possuem potências nos resultados aos cuidadores. As intervenções psicoeducacionais aumentam os saberes sobre a situação do paciente, preparando o cuidador para o cuidado, deixando-o seguro e autoconfiante, aperfeiçoando o cuidado. As psicoterapêuticas olham as necessidades singulares do cuidador e minimizam a sobrecarga com ações específicas. As intervenções psicossociais permitem a troca de saberes e possibilitam melhor enfrentamento de problemas, pois surgem como uma rede de apoio ao cuidador. CONCLUSÕES: Este estudo permitiu a caracterização e identificação das intervenções e suas potências para o cuidador familiar que precisa de atenção para que melhore a sua qualidade de vida e possa realizar um cuidado efetivo.

OBJECTIVE:To identify and characterize the interventions realizedwithcaregivers of chronic conditions adults assisted by home care. METHOD: In March 2021, 1,573 results were found in the Web of Science database, 633 results in PubMed, and one in the Lilacs database. The six steps of the integrative review were followed. After reading the abstracts and applying the exclusion criteria, 229 articles were selected for a full reading. Again, the inclusion and exclusion criteria were used, resulting in 39 articles, which comprised the scope of analysis of this study. Studies in English, Spanish and Portuguese were included. Descriptive analysis and content analysis were performed. RESULTS: The three forms of psychoeducational and psychotherapeutic or psychosocial intervention have potential in those afflicted with caregivers.Psychoeducational interventions increase knowledge about the patient's situation, preparecaregivers for care, leavethem safe and self-confident, improving care. Psychotherapeutics look at the caregiver's unique needsand minimize the burden with specific actions. Finally, psychosocial interventions allow the exchange of knowledge and enable better coping with problems, as they emerge as a support network for the caregiver.CONCLUSIONS:This study allowed the identification of interventions and their potential for the family caregiver who needs attention to improve their quality of life and provide adequate care.

OBJETIVO: Identificar e caracterizar las intervenciones utilizadas en los cuidadores de adultos con condiciones crónicas asistidos por la atención domiciliaria. METODOLOGÍA: En marzo de 2021, se encontraron 1.573 resultados en la base Web of Science, 633 resultados en la PubMed y 01 en la base LILACS. Se siguieron los seis pasos de la revisión integradora. Tras la lectura de los resúmenes y la aplicación de los criterios de exclusión, se seleccionaron 229 artículos para su lectura completa. Una vez más, se aplicaron los criterios de inclusión y exclusión, lo que dio como resultado 39 artículos, los cuales constituyeron el ámbito de análisis de este estudio. Se incluyeron estudios en inglés, español y portugués. Se realizó análisis descriptivo y análisis de contenido. RESULTADOS: Las tres formas de intervención, tanto las psicoeducativas como las psicoterapéuticas o las psicosociales, tienen potencialidades en los resultadoscon loscuidadores. Las intervenciones psicoeducativas incrementan los conocimientos sobre la situación del paciente, preparando al cuidador para los cuidados, haciéndole sentirse seguro y confiado en sí mismo, mejorando los cuidados. Las intervenciones psicoterapéuticas contemplan las necesidades únicas del cuidador y minimizan la sobrecarga con acciones específicas. Las intervenciones psicosociales permiten el intercambio de conocimientos y posibilitan un mejor afrontamiento de los problemas, ya que aparecen como una red de apoyo para el cuidador.CONCLUSIONES: este estudio permitió identificar las intervenciones y sus potencialidades para el cuidador familiar que necesita atención para mejorar su calidad de vida y proporcionar una atención eficaz.

Biochemical screening for SARS-CoV-2 main protease inhibitors.

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic represents a global challenge. SARS-CoV-2's ability to replicate in host cells relies on the action of its non-structural proteins, like its main protease (Mpro). This cysteine protease acts by processing the viruses' precursor polyproteins. As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 Mpro. A fluorescent assay was used to identify inhibitors in a compound library containing known drugs, bioactive molecules and natural products. These screens led to the identification of 13 inhibitors with IC50 values ranging from 0.2 µM to 23 µM. The screens confirmed several known SARS-CoV Mpro inhibitors as inhibitors of SARS-CoV-2 Mpro, such as the organo-mercuric compounds thimerosal and phenylmercuric acetate. Benzophenone derivatives could also be identified among the most potent screening hits. Additionally, Evans blue, a sulfonic acid-containing dye, could be identified as an Mpro inhibitor. The obtained compounds could be of interest as lead compounds for the development of future SARS-CoV-2 drugs.

Giardiasis Alters Intestinal Fatty Acid Binding Protein (I-FABP) and Plasma Cytokines Levels in Children in Brazil.

Giardiasis is an intestinal infection caused by ingestion of water or food contaminated with cysts of Giardia lamblia. Susceptibility is higher in children and overall prevalence can reach up to 90% in low-income areas, although outbreaks are also reported in developed countries. Both parasite and immune-mediated epithelial damage has been observed in vitro and in animal models. However, whether enterocytes are directly damaged during infection is not entirely known. Our goal was to identify whether plasma levels of intestinal fatty acid binding protein (I-FABP), a marker of enterocyte damage, are related to the immune response in giardiasis. Blood plasma was collected from 31 children (19 Giardia-positive) from a public day care in Rio de Janeiro, Brazil. The levels of I-FABP were increased in Giardia-infected children compared to children without detectable infection. There was no difference in I-FABP levels in giardiasis caused by different genetic assemblages of Giardia. Levels of IL-8 were decreased, while there was a trend to elevated IL-17 in the Giardia-positive children. A positive correlation was observed between I-FABP and IL-17 levels as well as TNF, suggesting that epithelial damage can be related to cytokine production during giardiasis. These results help elucidate the relationship between the disruption of the intestinal mucosal barrier and immune responses to G. lamblia in children.

Sepse neonatal - perfil microbiológico e sensibilidadeantimicrobiana em um hospital no Nordeste do Brasil / Neonatal sepsis - microbiological profile and antimicrobial sensitivity in a hospital in the Northeast of Brazil

Objetivo: Determinar a prevalência de microrganismos e o perfil de sensibilidade antimicrobiana em hemoculturas positivas de pacientes com infecção de corrente sanguínea na Unidade de Terapia Intensiva neonatal de um hospital no Nordeste brasileiro. Métodos: Estudo transversal, retrospectivo, com descrição quantitativa dos resultados de hemoculturas de neonatos admitidos na unidade terapia intensiva neonatal de um hospital do Nordeste brasileiro. Resultados: A sepse neonatal teve como principal etiologia bactérias Gram-positivas, responsáveis por 73,1% das culturas positivas, sendo o Staphylococcus Coagulase-negativa o principal agente, enquanto que 21,5% se deram por um agente Gram-negativo. As bactérias Gram-positivas apresentaram boa sensibilidade ao linezolida e à vancomicina e a maioria das Gram-negativas foi sensível a colistina, meropenem e imipenem. Todos os isolados de Staphylococcus coagulase negativa foram sensíveis ao linezolida, à vancomicina e à tigeciclina. Conclusão: O conhecimento das características relacionadas à sensibilidade e resistência antimicrobiana é fundamental para uma melhor abordagem ao paciente com sepse neonatal, promovendo um manejo mais direcionado que possibilita uma recuperação mais rápida do recém-nascido. O conhecimento adquirido com esse estudo possibilitará um tratamento mais eficiente em cada caso, com base no quadro apresentado pelo paciente e as características do agente causador.

Objective: To determine the prevalence of microorganisms and the antimicrobial sensitivity profile in positive blood cultures of patients with bloodstream infection in the neonatal Intensive Care Unit of a hospital in the Brazilian Northeast. Methods: Cross-sectional, retrospective study with quantitative description of hemoculture results of neonates admitted to the neonatal intensive care unit of a Brazilian Northeast hospital. Results: Neonatal sepsis had as its main etiology Gram-positive bacteria responsible for 73.1% of the positive cultures, with coagulase-negative Staphylococcus being the main agent, while 21.5% were due to a Gramnegative agent. Gram-positive bacteria showed good sensitivity to linezolid and vancomycin and most Gram-negative strains were susceptible to colistin, meropenem and imipenem. All coagulase-negative Staphylococcus isolates were sensitive to linezolid, vancomycin and tigecycline. Conclusion: Knowledge of the characteristics related toantimicrobial susceptibility and resistance is fundamental for a better approach to the patient with neonatal sepsis, promoting a more targeted management that allows a faster recovery of the newborn. The knowledge gained from this study will allow a more efficient treatment in each case, based on the patient's presentation and the characteristics of the causative agent

Perfil das lesões das vítimas de acidentes de motocicletas atendidas em hospital público / Profile of motorcycle accident injuries injury at a public hospital

Introdução:A motocicleta vem se destacando como o meio de transporte mais envolvido nos acidentes de trânsito, levando a altos índices de morbimortalidade. Objetivo: Caracterizar as vítimas e as lesões decorrentes de trauma por acidente de motocicleta atendidas em um hospital público. Metodologia:Estudo de caráter transversal do tipo descritivo com uma amostra de 53 internos por acidente de motocicleta no Hospital Estadual de Emergência e Trauma Senador Humberto Lucena. Resultados:Constatou-se que o gênero masculino foi o mais recorrente (88,7%), assim como a faixa etária dos 15 aos 35 anos (69,8%), solteiros (52,9%), ativos (77,3%), com segundo grau completo (50,9%) e renda familiar per caput <1 salário mínimo (73,6%). As fraturas (77,4%) e as lesões de superfície externa (69,8%) foram as mais frequentes. Os índices de gravidade das lesões (ISS) mais encontrados foram do tipo leve (79,2%), seguido do moderado (15,1%) e grave (5,7%). A região do corpo mais atingida foi membros/cintura pélvica (43,4%), porém a maior média de gravidade das lesões foi na região de cabeça/pescoço (2,9±1,0). Conclusão: A redução da morbimortalidade de acidentados de motocicleta depende da adoção de medidas preventivas baseadas no perfil das vítimas. (AU)

Introduction: Motorcycles have been highlighted as the most means of transportation involved in traffic accidents, leading to high morbidity and mortality rates. The objective was to characterize the victims and injuries resulting from motorcycle accident trauma treated at a public hospital. Methodology: A descriptive cross-sectional study with a sample of 53 hospitalized patients due to motorcycle accidents at Senator Humberto Lucena State Emergency and Trauma Hospital. Results: It was found that the male gender was the most recurrent (88.7%), as well as the age group from 15 to 35 years (69.8%), single (52.9%), active (77.3%), with high school degree (50 , 9%) and per capita family income of <1 minimum wage (73.6%). Fractures (77.4%) and external surface injuries (69.8%) were the most frequent. The most common injury severity indexes (ISS) were mild (79.2%), followed by moderate (15.1%) and severe (5.7%). The most affected body region was pelvic limbs / waist (43.4%), but the highest mean severity of injuries was in the head / neck region (2.9 ± 1.0). Conclusion: The reduction of motorcycle accident morbidity and mortality depends on the adoption of preventive measures based on the profile of the victims.(AU)