Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Egg allergy and yellow fever vaccination

Abstract Objective Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI). Methods Patients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour. Results 103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p =0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p =0,025). Thirty patients underwent the YFV desensitization protocol. Conclusion There is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.

Monitoramento e avaliação da cobertura vacinal da vacina contra febre amarela: revisão integrativa / Monitoreo y evaluación de la cobertura vacunal de la vacuna contra la fiebre amarilla: revisión integradora / Monitoring and evaluation of vaccination coverage of the yellow fever vaccine: integrative review

Objetivo: descrever as estratégias de monitoramento e avaliação da cobertura vacinal de vacina contra febre amarela (FA) no Brasil. Método: revisão integrativa nas bases Lilacs, BDENF, Medline e SciELO. Utilizou-se operadores booleanos e de truncamento para construir a estratégia de busca a partir das palavras chaves.: Monitoramento; Avaliação; Cobertura vacinal; Febre amarela. Cinco artigos foram selecionados. Resultados: Identificou-se estratégias de monitoramento da cobertura vacinal da vacina contra FA (ex.: cálculos de cobertura vacinal e de doses aplicadas; Monitoramento Rápido de Coberturas Vacinais, entre outras). Assim como estratégias de avaliação (ex.: alcance de meta da cobertura preconizada; número de casos confirmados de FA, entre outras).Conclusão: Além do alcance do objetivo, com construção de um quadro-síntese, pôde-se observar limitação do número de artigos encontrados e incipiência na elaboração de estudos nesta área.

Objective: to describe strategies for monitoring and evaluating vaccination coverage of yellow fever (YF) vaccine in Brazil. Method: integrative review in the Lilacs, BDENF, Medline and SciELO databases. Boolean and truncation operators were used to build the search strategy based on the keywords: Monitoring; Assessment; Vaccination coverage; Yellow fever. Five articles were selected. Results: strategies for monitoring vaccination coverage of the YF vaccine were identified (e.g. calculations of vaccination coverage and doses applied; Rapid Monitoring of Vaccination Coverage, among others). As well as evaluation strategies (e.g. reaching the coverage target recommended; number of confirmed cases of AF, among others). Conclusion: in addition to achieving the objective, with the construction of a summary table, it was possible to observe a limitation in the number of articles found and a lack of development in studies in this area.

Objetivos:describir estrategias para el seguimiento y evaluación de la cobertura vacunal de la vacuna contra la fiebre amarilla (FA) en Brasil. Método: revisión integrativa en las bases Lilacs, BDENF, Medline y SciELO. Se utilizaron operadores booleanos y de truncamiento para construir la estrategia de búsqueda basada en las palabras clave: Monitoreo; Evaluación; Cobertura de vacunación; Fiebre amarilla. Se seleccionaron cinco artículos. Resultados: se identificaron estrategias para el seguimiento de la cobertura vacunal de la vacuna contra la FA (ej., cálculos de cobertura vacunal y dosis aplicadas; Monitoreo Rápido de la Cobertura Vacunal, entre otros). Así como estrategias de evaluación (ej. alcanzar la meta de cobertura recomendada; número de casos confirmados de FA, entre otros). Conclusión: además de lograr el objetivo, con la construcción de un cuadro resumen, se puede observar una limitación en el número de artículos encontrados y una incipiencia en el desarrollo de estudios en esta área.

Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

The Connotation and Clinical Significance of “Spleen Governs Time” based on the Zangxiang （藏象） Time-space View / 中医杂志

There are different views on the theory of “spleen governs time”， which is still a hot spot in the study of Zangxiang （藏象） theory. Based on Zangxiang time-space view， it is found that the thinking mode of the spleen governing time theory follows space-time logic. It is believed that the different time views of the spleen governing time are all formed based on the space view that the spleen belongs to earth and resides in the center， and the zang time theory is developed with the unified time and space logic. Guided by Zangxiang time-space view， the origin of the spleen belonging to earth and residing in the center is traced， and the theoretical connotation and its clinical application of spleen governing time under different time-space logic are explored with reference to the four season and five zang theory， five season and five zang theory， six season and six zang theory， and eight season and eight zang theory.

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443 / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration.@*METHODS@#HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR.@*RESULTS@#HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05).@*CONCLUSION@#HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

Francisco Javier Muñiz. Cirujano de guerra / Francisco Javier Muñiz. War Surgeon

Francisco Javier Muñiz nació en Monte Grande en 1795 y se graduó de médico en la Facultad de Medicina de la Universidad de Buenos Aires en 1822. Además de la medicina y la paleontología, Muñiz se desempeñó como cirujano de guerra en la guerra con el Brasil y en la guerra de la Triple Alianza. En 1871, encontrándose jubilado, se ofrece como voluntario en la lucha contra la epidemia de fiebre amarilla que asoló a la ciudad de Buenos Aires provocando 14.467 muertos. Muñiz falleció el 8 de abril de 1871 en cumplimiento del deber, contagiado de fiebre amarilla. Médico, periodista, paleontólogo, descubridor de la vacuna nativa contra la viruela y realizador de apuntes de lingüística, Francisco Javier Muñiz, representa uno de los grandes ejemplos para la sociedad argentina. (AU)

Francisco Javier Muñiz was born in Monte Grande in 1795 and graduated as a physician from the Faculty of Medicine of the University of Buenos Aires in 1822. In addition to medicine and paleontology, Muñiz served as a military surgeon in the War with Brazil and in the War of the Triple Alliance. In 1871, when he was retired, he volunteered to fight the yellow fever epidemic that devastated the city of Buenos Aires, causing 14,467 deaths. Muñiz died in the line of duty on April 8, 1871, infected with yellow fever. Doctor, journalist, paleontologist, discoverer of the native vaccine against smallpox and linguistic note-taker, Francisco Javier Muñiz is one of the great examples for Argentinian society. (AU)

Momentos históricos de la epidemiología en el Hospital Muñiz, Buenos Aires, Argentina / Historical events in epidemiology, at the Muñiz Hospital, Buenos Aires, Argentina

Resumen El hospital Muñiz es una institución con patrimonio histórico, cultural y sanitario. Se realiza aquí un análisis histórico de las diferentes epidemias/pandemias y bro tes, valorando los manejos epidemiológicos (vigilancia, prevención, control y gestión de emergencias) en la institución y el porqué de su arquitectura. Para tal fin se lleva a cabo una revisión sistemática de la literatura sobre la historia del hospital Muñiz y sus referentes desde 1980 hasta 2023, siguiendo el formato PRISMA. Se encontraron 36 publicaciones que cumplieron con los criterios metodológicos y epidemiológicos requeridos. La revisión muestra los problemas relevantes en salud, los eventos presentes en una epidemia/pandemia, la importancia de medidas de prevención y de evaluar la necesidad de un sistema de vigilancia epidemiológica continuo, así como el aporte de referentes históricos metodológicos que permita obtener información útil en el área de salud. Hemos abordado grandes momentos históricos en la epidemiología explicando el manejo de las enfermedades o epidemias/pandemias en el hospital Muñiz, las cuales se relacionaron en gran medida a la sociedad de la época (paradigmas). Cabe resaltar que el crecimiento poblacional extendió las enfermedades a lo largo del planeta generando amenazas y que las epide mias/pandemias transformaron las sociedades y muy posiblemente han cambiado decisivamente el curso de la historia, tal como paso con la pandemia por COVID-19.

Abstract The Muñiz hospital is an institution with historical, cultural and health heritage. A historical analysis of the different epidemics/pandemics and outbreaks is carried out here, assessing the epidemiological man agement (surveillance, prevention, control and emer gency management) in the institution and the reason for its architecture. To this end, a systematic review of the literature on the history of the Muñiz hospital and its references was carried out, since 1980 to 2023, following the PRISMA format. Thirty-six publications were found that met the required methodological and epidemiological criteria. The review shows the relevant health problems, the events present in an epidemic/ pandemic, the importance of preventive measures and to assess the need for a continuous epidemiological surveillance system, as well as the contribution of historical methodological references that allow obtaining useful information in the health area. We have addressed great historical moments in epidemiology, explaining the management of diseases or epidemics/pandemics at the Muñiz hospital, which were largely related to the society of the time (paradigms). It should be noted that population growth spread diseases throughout the planet, generating threats, and that epidemics/pan demics transformed societies and quite possibly have decisively changed the course of history, as happened with the COVID-19 pandemic.

Hesitação da vacina da febre amarela e sua relação com influências contextuais, individuais ou de grupo e questões específicas da vacina: uma revisão de escopo / Yellow fever vaccine hesitancy and its relationship with contextual, individual, or group influences and vaccine-specific issues: a scoping review

Resumo A hesitação vacinal é um fenômeno com potencial para reduzir as taxas de cobertura vacinal, como observado na vacina contra febre amarela (VFA), propiciar epidemias e a reintrodução de doenças imunopreveníveis controladas. O objetivo deste estudo é mapear junto à literatura científica a relação entre a falta de informação, a segurança da vacina e os eventos adversos e a hesitação vacinal da VFA. Foi realizada uma revisão de escopo nas bases Biblioteca Virtual em Saúde (BVS), National Library of Medicine (PubMed), SCOPUS, Embase e Web of Science utilizando descritores controlados (DeCS/MeSH) e não controlados. Foram selecionados 11 artigos publicados nos idiomas inglês, espanhol e português, sem delimitação de tempo e que atenderam aos critérios de inclusão. Estiveram relacionados à hesitação vacinal da VFA informações falsas, conhecimento inadequado sobre o imunizante, falta de tempo para se vacinar, aceitação da vacina, insegurança na vacina e medo dos eventos adversos. Este estudo reforça a importância do acesso a informações adequadas, orientações sobre a segurança e os eventos adversos da VFA e pode auxiliar na elaboração de estratégias de saúde pública para mitigar a hesitação vacinal.

Abstract Vaccine hesitancy is a phenomenon with the potential to reduce vaccination coverage rates, as observed with the yellow fever vaccine (YFV), leading to epidemics and the reintroduction of controlled immunopreventable diseases. This study, together with the scientific literature, aims to map the relationship among the lack of information, vaccine safety and adverse events, and vaccine hesitancy concerning YFV. A scoping review was conducted in the Virtual Health Library (VHL), National Library of Medicine (PubMed), SCOPUS, Embase, and Web of Science databases, using controlled (DeCS/MeSH) and uncontrolled descriptors. In this work, we selected eleven articles, published in English, Spanish, and Portuguese, with no time limits, which met the inclusion criteria. False information, inadequate knowledge about the immunizer, lack of time to take a vaccination, acceptance of the vaccine, vaccine safety, and fear of adverse events were related to vaccine hesitancy. This study reinforces the importance of access to adequate information, provides guidance on YFV safety and adverse events, and can aid in the development of public health strategies to mitigate hesitancy.

O lampejo dos rastros nos intervalos da montagem: notas metodológicas sobre a incursão em arquivos concernentes à febre amarela e à gripe espanhola / The flash of traces in the montage intervals: methodological notes on the incursion into Yellow Fever and Spanish Flu archives / El destello de los rastros en los intervalos del montaje: apuntes metodológicos sobre la incursión en archivos concernientes a la fiebre amarilla y a la gripe española

No presente artigo, tecemos reflexões e apresentamos conceitos que têm orientado uma pesquisa nos registros de arquivos sobre a febre amarela e a gripe espanhola, nos acervos da Fundação Oswaldo Cruz, da Biblioteca Nacional e do Arquivo Nacional. A pesquisa é centrada na busca dos rastros e das ruínas desses eventos epidêmicos, mediante o método da montagem e com a perspectiva do limiar. Buscamos, por meio dessas materialidades, criar intervalos, experimentar e tecer brechas que prefiguram outros possíveis. Defendemos que, ao manejar, por meio da fabulação crítica, as formas como uma epidemia se faz aparecer, habilitamos a elaboração de uma imaginação política capaz de conferir ao futuro outras possibilidades e outros agenciamentos que não sejam a catástrofe e a melancolia

In this article we reflect on the presented concepts that have guided research in the archival records of Yellow Fever and Spanish Flu in the collections of the Fundação Oswaldo Cruz (Oswaldo Cruz Foundation), the Biblioteca Nacional (National Library), and the Arquivo Nacional (National Archive). The research is centered on the search for the traces and ruins of those epidemic events, through the method of montage and from the perspective of the threshold. We seek, by means of these materialities, to create intervals, to experiment, and to weave gaps that prefigure other possibilities. We argue that, by coping with, through critical fabulation, the ways in which an epidemic makes itself appear, we enable the elaboration of a political imagination capable of giving the future other possibilities and arrangements that are not the catastrophe and the melancholy

En el presente artículo hacemos reflexiones y presentamos conceptos que han guiado una investigación sobre los registros archivísticos de la fiebre amarilla y la gripe española en los acervos de la Fundação Oswaldo Cruz (Fundación Oswaldo Cruz), de la Biblioteca Nacional (Biblioteca Nacional y del Arquivo Nacional (Archivo Nacional). La investigación se centra en la búsqueda de los rastros y las ruinas de esos eventos epidémicos, mediante el método del montaje y la perspectiva del umbral. Buscamos, por medio de estas materialidades, crear intervalos, experimentar y tejer brechas que prefiguren otras posibilidades. Argumentamos que manejando, a través de la fabulación crítica, las formas en que se hace aparecer una epidemia, posibilitamos la elaboración de una imaginación política que dé al futuro otras posibilidades y disposiciones que no sean la catástrofe y la melancolía

A case of successfully treated self-ingested yellow phosphorous poisoning in a known case of epilepsy

Ratol is a rodenticide (rat killer paste) that contains yellow phosphorus, a dangerous toxin that harms the gastrointestinal, hepatic, cardiovascular, and renal systems both locally and systemically. The liver is one of these that is most frequently injured, and the most terrifying result is acute liver failure with coagulopathy. A 25-year-old male who is a known case of epilepsy and was on medication was brought to the Emergency Department by his mother with an alleged history of consuming approximately 15 g of Ratol paste mixed in water 5 days before presentation to our hospital at around 5 pm at his residence. The patient sustained nausea and vomiting during the following day of consumption and was treated for the same in a nearby hospital. The main element in lowering morbidity and death is the provision of effective and timely supportive care.

Accuracy of yellow fever case definition of epidemiologic surveillance, São Paulo, 2018

ABSTRACT OBJECTIVE To evaluate the accuracy of yellow fever (YF) suspected case definitions from the Brazilian Ministry of Health (BMH) and World Health Organization (WHO), as well as propose and evaluate new definitions of suspected cases, considering confirmed and discarded cases. METHODS The retrospective study was conducted at the Instituto de Infectologia Emílio Ribas (IIER), using the Epidemiologic Surveillance Form of YF cases. From the confirmed and discarded cases of YF, a logistic regression model was developed. The independent variables were used in a proposed definition of a suspected case of YF and its accuracy was evaluated. RESULTS In total, 113 YF suspect cases were reported, with 78 confirmed (69.0%). The definitions by BMH and WHO presented low sensitivity, 59% and 53.8%, and reduced accuracy, 53.1% and 47.8%, respectively. Predictive factors for YF were thrombocytopenia, leukopenia, and elevation of transaminases greater than twice normal. The definition including individual with acute onset of fever, followed by elevation of ALT or AST greater than twice the reference value AND leukopenia OR thrombocytopenia presented high sensitivity (88.3%), specificity (62.9%), and the best accuracy (80.4%), as proposed in the model. CONCLUSION The YF suspected case definitions of the BMH and the WHO have low sensitivity. The inclusion of nonspecific laboratory tests increases the accuracy of YF definition.

Evaluation of superabsorbent polymer (SAP) in oviposition traps used in the integrated control of Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) (Diptera:Culicidae)

ABSTRACT Background: Egg collection traps have been studied to assist in the integrated control of arbovirus vectors. Many enhancements have been made over the years. Methods: This study evaluated the use of a hydrated superabsorbent polymer (SAP) in the egg collection of Aedes aegypti and Aedes albopictus in ovitraps. An experiment was conducted in the laboratory to determine the minimum concentration of the product to be used in traps in the field to prevent the development of larvae into adults. In the field, the use of polymers has been evaluated using a traditional model of ovitraps. The positive ovitrap index and mean number of eggs per trap indicator were calculated. Results: In the laboratory, the larvae did not successfully develop to the adult stage, even at the lowest SAP concentration. In the field, the results showed that ovitraps with SAP proved to be effective for egg collection from both species. It was possible to identify sites with the highest concentration of species and expose the ovitraps for a longer period without larval development. Conclusions: There is a need for studies on the adequacy of this technology for control programs. However, the results showed that ovitraps with hydrogel were potentiated to capture eggs, configuring themselves as another tool for vector control.

Reanálisis del estudio de Carlos J. Finlay acerca del mosquito como vector de la fiebre amarilla

Introducción: El primer registro de la asociación causal entre el mosquito Aedes aegypti, y la transmisión de la fiebre amarilla, lo constituyó la comunicación presentada por Carlos J. Finlay a la Academia de Ciencias de La Habana en 1881. El científico cubano mostró los resultados de la inoculación, por picadura de mosquito infectado, en cinco sujetos de un conjunto de 20 personas sanas. Objetivo: Reanalizar la evidencia mediante la aplicación de técnicas estadísticas aún no desarrolladas en tiempo del científico cubano, y evaluar la fortaleza de la evidencia causal. Métodos: Los resultados se analizaron mediante el test exacto de Fisher, el factor de Bayes y la diferencia de riesgos, el riesgo relativo y el odds ratio de la asociación. Se valoró la fortaleza de la evidencia de la asociación causal mediante criterio estadístico sin desconocer los criterios de causalidad más actualizados. Resultados: El test exacto de Fisher fue altamente significativo (p= 0,009), y el factor de Bayes (24,9) resultó compatible con una evidencia fuerte a favor de la asociación entre la inoculación y el desarrollo de la enfermedad. También apoyaron la asociación, la diferencia de riesgos (0,55; IC 95 %: 0,15-0,96), el riesgo relativo (18,7; IC 95 %: 1,12-3-10,3) y el odds ratio (43,4; IC 95 %: 1,68-11-19,7). Conclusiones: Los resultados de Finlay resultaron robustos, y se ajustaron a los criterios de causalidad para explicar la transmisión de la fiebre amarilla por el mosquito.

Introduction: The first record of the causal association between the Aedes aegypti mosquito and the transmission of yellow fever was the communication submitted by Carlos J. Finlay to the Havana Academy of Sciences in 1881. The Cuban scientist showed the results of inoculation, by infected mosquito bite, in five subjects from a group of 20 healthy people. Objective: To revise the evidence through the use of statistical techniques not yet developed at the time of the Cuban scientist and to evaluate the strength of the causal evidence. Methods: Results were analyzed using Fisher's exact test, Bayes factor, and risk difference, relative risk, and odds ratio of association. The strength of the evidence of the causal association was assessed using statistical criteria minding the most up-to-date causality criteria. Results: Fisher's exact test was highly significant (p = 0.009), and the Bayes factor (24.9) was compatible with strong evidence in favor of the association between inoculation and disease development. The association was also supported by the risk difference (0.55; 95% CI: 0.15-0.96), the relative risk (18.7; 95% CI: 1.12-310.3), and the odds ratio (43.4; 95% CI: 1.68-1119.7). Conclusions: Finlay's results were robust, and adjusted to the causality criteria to explain the transmission of yellow fever by mosquitoes.

Effects of migration rates and vaccination on the spread of yellow fever in Latin American communities / Efectos de las tasas de migración y de la vacunación en la propagación de la fiebre amarilla en comunidades de América Latina / Efeitos das taxas de migração e vacinação na propagação da febre amarela em comunidades latino-americanas

ABSTRACT Objective. To assess how relevant the flow of people between communities is, compared to vaccination and type of vector, on the spread and potential outbreaks of yellow fever in a disease-free host community. Methods. Using a SEIRV-SEI model for humans and vectors, we applied numerical simulations to the scenarios: (1) migration from an endemic community to a disease-free host community, comparing the performance of Haemagogus janthinomys and Aedes aegypti as vectors; (2) migration through a transit community located on a migratory route, where the disease is endemic, to a disease-free one; and (3) effects of different vaccination rates in the host community, considering the vaccination of migrants upon arrival. Results. Results show no remarkable differences between scenarios 1 and 2. The type of vector and vaccination coverage in the host community are more relevant for the occurrence of outbreaks than migration rates, with H. janthinomys being more effective than A. aegypti. Conclusions. With vaccination being more determinant for a potential outbreak than migration rates, vaccinating migrants on arrival may be one of the most effective measures against yellow fever. Furthermore, H. janthinomys is a more competent vector than A. aegypti at similar densities, but the presence of A. aegypti is a warning to maintain vaccination above recommended levels.

RESUMEN Objetivo. Evaluar la importancia del flujo de personas entre comunidades, en comparación con la vacunación y el tipo de vector, para la propagación y los posibles brotes de fiebre amarilla en una comunidad de acogida libre de la enfermedad. Métodos. Con el empleo de un modelo SEIRV—SEI para personas y vectores, aplicamos simulaciones numéricas a las siguientes situaciones hipotéticas: 1) migración desde una comunidad con endemicidad a una comunidad de acogida libre de la enfermedad, en la que se compararon los resultados producidos por Haemagogus janthinomys y Aedes aegypti como vectores; 2) migración a través de una comunidad de tránsito situada en una ruta migratoria, donde la enfermedad es endémica, hacia otra comunidad libre de la enfermedad; y 3) efectos de tasas de vacunación diferentes en la comunidad de acogida, tomando en consideración la vacunación de las personas migrantes a su llegada. Resultados. Los resultados no muestran diferencias notables entre las situaciones 1 y 2. En cuanto a la aparición de brotes, tanto la cobertura vacunal en la comunidad de acogida como el tipo de vector tienen más importancia que las tasas de migración; y H. janthinomys muestra mayor eficacia que A. aegypti. Conclusiones. Dado que, para determinar la aparición de un posible brote, la vacunación tiene mayor importancia que las tasas de migración, la vacunación de las personas migrantes a su llegada puede ser una de las medidas más eficaces contra la fiebre amarilla. Además, a densidades similares, H. janthinomys es un vector más competente que A. aegypti, por lo que la presencia de A. aegypti constituye una señal de alerta para mantener la vacunación por encima de los niveles recomendados.

RESUMO Objetivo. Avaliar a relevância do fluxo de pessoas entre comunidades em comparação com a vacinação e tipo de vetor para a propagação e potenciais surtos de febre amarela em uma comunidade de destino livre da doença. Métodos. Usando um modelo SEIRV-SEI para humanos e vetores, foram aplicadas simulações numéricas aos seguintes cenários: (1) migração de uma comunidade endêmica para uma comunidade de destino livre da doença, comparando o desempenho de Haemagogus janthinomys e de Aedes aegypti como vetores; (2) migração através de uma comunidade de trânsito localizada em uma rota migratória, onde a doença é endêmica, para uma comunidade de destino livre da doença; e (3) efeitos de diferentes taxas de vacinação na comunidade de destino, considerando-se a vacinação dos migrantes ao chegarem. Resultados. Os resultados não revelaram diferenças marcantes entre os cenários 1 e 2. O tipo de vetor e a cobertura vacinal na comunidade de destino são mais relevantes para a ocorrência de surtos do que as taxas de migração; o vetor H. janthinomys é mais efetivo do que A. aegypti. Conclusões. Na medida em que a vacinação é mais determinante para um potencial surto que as taxas de migração, a vacinação de migrantes na chegada pode ser uma das medidas mais efetivas contra a febre amarela. Além disso, o H. janthinomys é um vetor mais competente do que o A. aegypti em densidades similares, mas a presença de A. aegypti é um alerta para manter a vacinação acima dos níveis recomendados.

Antibacterial activity: a comparism of ripe and unripe extracts of two varieties (red and yellow) of cashew apple (anacardium occidentale) on some clinical bacterial isolates

The emergence of pathogenic bacteria that are resistant to several antibiotics has recently presented a significant challenge to the healthcare system. Therefore, an alternative source of antimicrobial agents is needed. The study aimed to compare the antibacterial activities of aqueous and ethanol extracts of ripe and unripe fruits of red and yellow varieties of Anacardium occidentale against Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Staphylococcus aureus. Cold maceration method of extraction was used using water and ethanol. Antibacterial activities of the extracts against the isolates were evaluated by agar diffusion method while minimum inhibitory concentration (MIC) was determined using broth dilution method. In the determination of the antibacterial activities of all the extracts, the highest zones of inhibition were shown by ethanolic extracts of both ripe red cashew (25 mm) and yellow cashew (26 mm) against Escherichia coli. Both the aqueous and ethanolic extracts of unripe red and yellow cashew had no antibacterial effect against Klebsiella pneumoniae and Pseudomonas aeruginosa. As well, both aqueous and ethanol extracts of ripe red and yellow cashew and ethanolic extract of ripe yellow cashew inhibited all the test organisms. Minimum inhibitory concentration ranged from 50 to 150 mg/ml. At 100 mg/ml, both ethanolic extracts of ripe red and yellow cashew were bactericidal to Escherichia coli while aqueous extract of ripe red cashew was bactericidal to Escherichia coli at 150 mg/ml. The antibacterial activities of A. occidentale apple (fruit) extracts underscore the credence to the efficacy of their use as traditional remedy against some human ailments.

Perturbations in gastrointestinal tract microbiota composition and function in individuals with yellow-greasy tongue coating / 数字中医药（英文）

@#【Objective】  To study the composition and function of tongue coating (TC) and gastrointestinal tract (GIT) microbiota in participants with yellow-greasy tongue coating (YGTC), and to explore the representative metabolite markers and pathways in this group. 【Methods】  Subjects with YGTC or thin-white tongue coating (TWTC) were recruited from December 1, 2021 to October 30, 2022, and the TC and fecal samples were collected. Samples were subjected to both whole-genome shotgun (WGS), and 16S rRNA gene sequencing. The α-diversity analysis, principal component analysis (PCA), and Spearman correlation analysis were performed for two groups. Ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC–MS/MS) analysis was used to analyze metabolomics and enrichment of metabolic pathways. 【Results】  The results revealed 20 YGTC participates and 19 TWTC participates. At the genus level, the dominant bacterial species of TC flora and intestinal flora in the two groups were roughly the same, but the relative kurtosis difference was marked, and the abundance of potentially pathogenic bacteria in TC and fecal samples of YGTC subjects was higher. There were 9 down-regulated microorganisms in the TC samples, 26 down-regulated microorganisms, and 6 up-regulated microorganisms in YGTC subjects. The α-diversity analysis indicated that the Chao and abundance-based coverage estimator (ACE) indices of TC bacteria in the YGTC subjects showed a decreasing trend, but the difference was not statistically significant (P > 0.05). The α-diversity of fecal samples and the Chao and ACE indices decreased significantly (P < 0.05). PCA showed that the microflora structure of TC and fecal samples were significantly different between the two groups. Spearman correlation analysis showed that there was no correlation between TC and fecal microorganisms at phyla and genus levels in the same subjects (P > 0.05). The metabolomics results demonstrated that fumarate reductase, V/A ATPase, and phosphatidylethanolamine were increased, and glycerate-3p, UDP-glucose, and quinone oxidoreductase metabolites were decreased in YGTC TC samples. Inosine monophosphate (IMP), uridine monophosphate (UMP), and gamma-aminobutyric acid(GABA) were increased in YGTC fecal samples, while the contents of ribo-5P, histidine, biotin,and cobalamin were decreased. Metabolic pathway analysis indicated that the abundance of the TC and fecal samples of the YGTC subjects was relatively low in various metabolic pathways, including amino acid metabolism, carbohydrate metabolism, nitrogen metabolism, and energy metabolism. 【Conclusion】  Structural and functional changes in TC and GIT microbiota or metabolite markers could be potential biological bases of YGTC formation.

Exploration of the theory of Renying Cunkou pulse method recorded in the Yellow Emperor's Inner Canon / 中国针灸

Renying Cunkou pulse method is one of the classical pulse methods of acupuncture-moxibustion in the Yellow Emperor's Inner Canon, which is also a classical clinical paradigm for diagnosing and treating meridian diseases in the ancient times. Based on comprehensive review of literature and clinical practice, this paper reveals that this method compares the size of the neck Renying pulse with hand Cunkou pulse to determine the change of yin-yang and excess-deficiency identifying the affected meridians. The jing-well, xing-spring, and shu-stream points of the surface and interior meridians of affected meridians are mainly selected to regulate deficiency and excess through reinforcing and reducing methods. The Renying Cunkou pulse method possesses a simple and practical medical theory, easy diagnostic procedure, and clear meridian selection for acupuncture-moxibustion treatment, warranting further exploration of its essence and diagnostic therapeutic principles.

Clinical Treatment Ideas of “Treatment with Combination of Diverse Methods and Prescriptions” in TheInner Canon of Yellow Emperor （《黄帝内经》） / 中医杂志

As a basic source for the theoretical system of traditonal Chinese medicine （TCM）， the Inner Canon of Yellow Emperor （《黄帝内经》） made the point of “treatment with combination of diverse methods and prescriptions”，which is one of the characteristics of TCM in treating diseases. This paper discussed the therapeutic idea of “diverse methods and prescriptions” from five dimensions， including time， population， regions， diseases， and treatments， and proposed that “combined treatment” is an effective measure to embody the idea of “diverse methods and prescriptions”. That is to say， by taking the combination of the concept of holism and syndrome differentiation and treatment as the starting point， combining pharmacological and non-pharmacological therapies， and treating both internal and external diseases through multiple ways and methods， the goal to treat the disease at the root， and keep yin at peace and yang compact can be achieved. Finally， it is suggested to guide the clinical practice with “treatment with combination of diverse methods and prescriptions”， providing new ideas for clinical diagnosis and treatment.

Health risk assessment of phthalic acid esters contamination in market-available yellow rice wine in Huzhou City / 预防医学

Objective@#To investigate the contamination of phthalic acid esters (PAEs) and assess the health risk of PAEs contamination in market-available yellow rice wine in Huzhou City, Zhejiang Province, so as to provide the safety safeguard for consuming yellow rice wine.@*Methods@#Yellow rice wine samples were collected from markets in Huzhou City from 2021 to 2022, and 16 PAEs were determined in yellow rice wine using magnetic solid-phase extraction coupled with gas chromatography-tandem mass spectrometry. The carcinogenic and non-carcinogenic risks of PAEs were evaluated using the health risk models proposed by United States Environmental Protection Agency.@*Results@#A total of 75 yellow rice wine samples were collected, and 44 samples were detected with PAEs contamination (58.67%). Dimethyl phthalate (DMP), di-isobutyl phthalate (DIBP) and di-butyl phthalate (DBP) were detected, and there were 17 samples (22.67%) detected with DBP overdose (DMP and DIBP had no limit standard). DMP, DBP and DIBP, which were not classified as Class 2B and higher carcinogens by WHO's International Agency for Research on Cancer, had no definitive carcinogenic risks. Under mean PAEs, the five types of yellow rice wine all had no carcinogenic risks. Under 75% percentile of PAEs concentrations, the DBP in beverage wine with plastic packaging had a carcinogenic risk score of 1.207 5, with a gross carcinogenic risk score of 1.207 5. Under the maximum PAEs concentration, the ross carcinogenic risk scores of cooking wine with plastic packaging, beverage wine with plastic packaging, beverage wine with glass bottle packaging, and beverage wine with jar packaging were 2.751 0, 2.782 0, 1.298 2 and 2.944 0, presenting non-carcinogenic risks.@*Conclusion@#There is PAEs contamination in market-available yellow rice wine in Huzhou City, and no carcinogenic risk is evaluated. Non-carcinogenic health risk requires to be given a high priority.