Crise global da atenção primária à saúde / Global crisis in primary health care / Crisis global de la atención primaria

Enquanto no Norte Global se discute uma crise na Atenção Primária à Saúde, a maioria dos países nunca chegou a constituir sistemas de saúde baseados propriamente numa atenção primária robusta. Nesse cenário, o Brasil apresenta uma tendência mais favorável, com conquistas importantes para a atenção primária e a medicina de família e comunidade nos últimos dez anos. Restam desafios a serem superados para que o Sistema Único de Saúde alcance níveis satisfatórios de acesso a seus serviços, com profissionais adequadamente formados e valorizados pela população.

While the Global North is discussing a crisis in primary health care, the majority of countries have never managed to establish health systems based on robust primary care. Brazil presents a more favorable trend, with important achievements for primary care and family practice over the last ten years. There are still challenges to be overcome so that the Unified Health System achieves satisfactory levels of access to its services, with professionals who are properly trained and valued by the public.

Mientras que en el Norte Global se habla de una crisis de la atención primaria, la mayoría de los países nunca han creado realmente sistemas sanitarios basados en una atención primaria robusta. Brasil, muestra una tendencia más favorable, con importantes logros para la atención primaria y la medicina familiar y comunitaria en los últimos diez años. Aún quedan retos por superar para que el Sistema Único de Salud alcance niveles satisfactorios de acceso a sus servicios, con profesionales debidamente formados y valorados por la población.

O (des)cuidado em saúde às pessoas LGBTQIAP+ dispensado por profissionais em unidades básicas de saúde / The (lack of)health care provided to LGBTQIAP+ people by professionals in primary care centers / El (des)cuidado en salud a las personas LGBTQIAP+ dispensado por profesionales en unidades básicas de salud

Objetivo: compreender o cuidado em saúde dispensado às pessoas LGBTQIAP+ por profissionais em Unidades Básicas de Saúde, a partir do referencial teórico da Política Nacional de Saúde LGBT (PNSILGBT) estabelecida pelo Sistema Único de Saúde (SUS). Método: estudo descritivo, com abordagem qualitativa, que entrevistou 12 profissionais de saúde da Atenção Básica. Os dados coletados passaram pela Análise Lexical utilizando-se do software IRAMUTEQ. Resultados: emergiram três categorias temáticas que possibilitaram compreender que os profissionais reconhecem as violências praticadas na assistência a essa população, as barreiras no acesso e as dificuldades enfrentadas por pessoas LGBTQIAP+. Considerações finais: o desconhecimento das políticas e a não percepção das consequências dessas ações para a saúde dessa população remete muito mais ao (des)cuidado do que efetivamente ao cuidado condizente as suas reais necessidades em saúde.

Objective: to understand the health care provided to LGBTQIAP+ people by professionals in Primary Care Centers, based on the theoretical framework of the National LGBT Health Policy (PNSILGBT) established by the Unified Health System (SUS). Method: a descriptive study with a qualitative approach, which interviewed 12 primary care health professionals. The data collected was subjected to Lexical Analysis using the IRAMUTEQ software. Results: Three thematic categories emerged which made it possible to understand that professionals recognize the violence practiced in assisting this population, the barriers to access and the difficulties faced by LGBTQIAP+ people. Final considerations: the lack of knowledge of the policies and the lack of perception of the consequences of these actions for the health of this population leads much more to (lack of)care than to care in line with their real health needs.

Objetivo: comprender el cuidado en salud brindado a las personas LGBTQIAP+ por profesionales en Unidades Básicas de Salud, partiendo del marco teórico de la Política Nacional de Salud LGBT (PNSILGBT) establecida por el Sistema Único de Salud (SUS). Método: estudio descriptivo, con enfoque cualitativo, que entrevistó a 12 profesionales de salud de la Atención Básica. Los datos recogidos fueron analizados mediante Análisis Léxico utilizando el software IRAMUTEQ. Resultados: surgieron tres categorías temáticas que permitieron comprender que los profesionales reconocen las violencias ejercidas en la asistencia a esta población, las barreras en el acceso y las dificultades enfrentadas por personas LGBTQIAP+. Consideraciones finales: el desconocimiento de las políticas y la no percepción de las consecuencias de estas acciones para la salud de esta población reflejan mucho más el (des)cuido que efectivamente el cuidado acorde a sus reales necesidades en salud.

Uso da adaptação transcultural nos cursos de pós-graduação em Enfermagem / Use of cross-cultural adaptation in Postgraduate Nursing courses / Uso de la adaptación transcultural en las carreras de grado en Enfermería

Objetivo: analisar a produção científica brasileira, na Pós-Graduação em Enfermagem, que utilizou o método de adaptação transcultural. Método: estudo documental, com busca realizada na Biblioteca Digital de Teses e Dissertações, que resultou em 140 dissertações e 72 teses para análise, oriundas de Programas de Pós-Graduação da região Sudeste, seguida das regiões Nordeste, Sul e Centro-Oeste, sem representação da região Norte. Resultados: os instrumentos adaptados foram, em sua maioria, procedentes do idioma inglês. Prevaleceram as pesquisas na área/campo Assistencial, destacando-se a linha de pesquisa Processo de Cuidar em Saúde e Enfermagem. Identificou-se descompasso entre o que é produzido na área e o que é recomendado internacionalmente. Conclusão: verificou-se aumento na utilização da adaptação transcultural como método de pesquisa, com persistência das assimetrias acadêmicas regionais e sem consenso sobre o referencial metodológico.

Objective: to analyze the Brazilian scientific production in Postgraduate Nursing education using the cross-cultural adaptation method. Method: documentary study with searches carried out in the Digital Library of Theses and Dissertations resulting in 140 Master's theses and 72 Doctoral dissertations for analysis originated from Postgraduate Programs carried out in the Southeast region of Brazil, followed by the Northeast, South and Midwest regions ­ there was no representation of the North region. Results: the adapted instruments were, mostly, originally written in English. Research in the Care area/field prevailed, highlighting the line of research called Health and Nursing Care Process. A gap between what is produced in the area and what is recommended internationally was identified. Conclusion: an increase in the use of cross-cultural adaptation as a research method was noticed, with the persistence of regional academic asymmetries and lack of consensus on the methodological framework.

Objetivo: analizar la producción científica brasileña, en el Postgrado en Enfermería, que utilizó el método de adaptación transcultural. Método: estudio documental, la búsqueda se realizó en la Biblioteca Digital de Tesis y Disertaciones, se obtuvieron 140 tesis de maestría y 72 tesis de doctorado para análisis, provenientes de Programas de Posgrado de la región Sudeste, seguida de las regiones Nordeste, Sur y Centro-Oeste, no se encontraron documentos de la región Norte. Resultados: los instrumentos adaptados fueron, en su mayoría, del idioma inglés. Predominaron las investigaciones en el área/campo Asistencial, se destacó la línea de investigación Proceso de Atención en Salud y Enfermería. Se identificó que lo que se produce en el área no coincide con lo que se recomienda a nivel internacional. Conclusión: se comprobó que aumentó el uso de la adaptación transcultural como método de investigación, que persisten las disparidades académicas regionales y que no hay consenso sobre el marco metodológico.

Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Termo de consentimento livre e esclarecido e sua relação com os procedimentos de preenchimento labial / Free and informed consent terms and its relationship with lip filling procedures

Introdução: Na medida em que envelhecemos os lábios estreitam-se, ocasionando perda de volume e contorno e como forma de minimizar este efeito fisiológico o preenchimento labial de escolha utilizado é o ácido hialurônico. É possível perceber efeitos adversos advindos do emprego deste material, e pelo fato da informação ao paciente ser assegurada pelo Código de Defesa do Consumidor e pelo fato da necessidade dos Cirurgiões-Dentistas terem de esclarecer seus pacientes, o Termo de Consentimento Livre e Esclarecido tornase necessário. Objetivo: identificar, por meio de aplicação de questionário, a percepção de profissionais que trabalham com Harmonização Orofacial em relação a necessidade do emprego do Termo de Consentimento Livre e Esclarecido (TCLE). O questionário apresentou 6 perguntas objetivas, que foram disponibilizadas na plataforma Google Forms®. Material e Método: os dados obtidos foram tabulados em uma planilha eletrônica do programa Microsoft Excel e após analisados descritivamente através de tabelas de frequência, porcentagens e gráficos estatísticos. Resultados: dentre os entrevistados foi constatado que a maioria, 87,5% dos especialistas em Harmonização Orofacial realizam o procedimento de preenchimento labial em sua rotina clínica, e 12,5% não. Conclusão: no presente estudo identificamos que os especialistas realizam o emprego do TCLE, em sua maioria, porém, alguns destes ainda negligenciam o seu uso(AU)

Introduction: As we age, the lips become thinner and to minimize this effect, the lip filler used is hyaluronic acid. It is possible to notice adverse effects arising from the use of this material, and it is extremely important that Dental Surgeons have to clarify their patients, the Free and Informed Consent Form becomes necessary. Objective: to identify, through the application of a questionnaire, the perception of professionals who work with Orofacial Harmonization in relation to the need to use the Free and Informed Consent Form (TCLE). The questionnaire presented 6 objective questions, which were made available on the Google Forms® platform. Materials and Methods: the data obtained were tabulated in a Microsoft Excel spreadsheet and then analyzed descriptively using frequency tables, percentages and graphs. Results: among those interviewed, it was found that the majority, 87.5% of specialists in Orofacial Harmonization perform the lip filling procedure in their clinical routine, and 12.5% do not. With the high percentage of 59.4%, it was possible to verify that the majority of professionals perform 1 to 3 procedures per month; 31.3% perform 4 to 9 procedures per month; and 9.4% of 10 or more monthly procedures. Conclusion: in the present study it was possible to identify that the majority of specialists in Orofacial Harmonization use the informed consent form, however, some of them still neglect its use(AU)

Abriendo puertas para la vida: Programa de prevención de conductas suicidas a través de docentes Gatekeepers / Opening doors to life: A suicidal behavior prevention program involving Gatekeeper teachers / Abrindo portas para a vida: Programa de prevenção ao comportamento suicida por meio de professores Gatekeepers

Introducción: El suicidio es la tercera causa de muerte de jóvenes entre 15 y 19 años. Ante esto, los ambientes escolares pueden favorecer el fomento de la salud mental de los adolescentes, permitir la identificación temprana de factores de riesgo y aportar en la prevención de conductas suicidas. Una de las estrategias de prevención es el entrenamiento de "gatekeepers". Objetivo: Determinar el efecto del programa "Abriendo Puertas para la Vida" sobre conocimientos, actitudes y prácticas en prevención de conductas suicidas en un grupo de profesores de secundaria de una institución educativa de San Juan de Pasto, Colombia. Materiales y métodos: Estudio preexperimental, con un grupo de intervención y medidas pre y pos-seguimiento. Participaron nueve docentes voluntarios durante dos jornadas de formación. Resultados: Se identificaron cambios positivos en conocimientos, actitudes y prácticas de los participantes entre pretest y postest, en la mayoría de las subdimensiones evaluadas; sin embargo, tres años después, estos cambios se mantuvieron tan solo en conocimientos sobre las conductas suicidas y en actitudes hacia la prevención. Conclusión: El programa "Abriendo Puertas para la Vida" evidenció efectividad y pertinencia, sin embargo, el mantenimiento de sus efectos requiere de acciones de seguimiento y acompañamiento a los docentes formados.

Introduction: Suicide is the third cause of death in young people aged between 15 to 19 years. Thus, school environments can promote mental health of adolescents through early identification of risk factors and prevention of suicidal behaviors. One prevention strategy is the training of "gatekeepers". Objective: To determine the impact of the "Opening Doors to Life" program on the knowledge, attitudes, and practices regarding prevention of suicidal behavior in a set of high school teachers from an educational institution in San Juan de Pasto, Colombia. Materials and methods: A pre-experimental study with an intervention group and pre- and post-follow-up measurements. Nine volunteer teachers participated during two training sessions. Results: Positive changes regarding knowledge, attitudes, and practices of the participants during pretest and posttest were observed for the majority of evaluated sub-dimensions. However, after three years, the positive measures prevailed only for knowledge about suicidal behavior and attitudes toward prevention. Conclusion: The "Opening Doors to Life" program showed effectiveness and relevance. However, maintaining its impact requires follow-up actions and support of trained teachers.

Introdução: O suicídio é a terceira causa de morte de jovens entre 15 e 19 anos. Diante disso, os ambientes escolares podem promover a promoção da saúde mental em adolescentes, permitir a identificação precoce de fatores de risco e contribuir para a prevenção do comportamento suicida. Uma das estratégias de prevenção é a formação de "gatekeepers". Objetivo: Determinar o efeito do programa "Abrindo Portas para a Vida" nos conhecimentos, atitudes e práticas na prevenção do comportamento suicida em um grupo de professores do ensino médio de uma instituição educacional em San Juan de Pasto, Colômbia. Materiais e métodos: Estudo pré-experimental, com grupo de intervenção e medidas pré e pós-acompanhamento. Nove professores voluntários participaram durante dois dias de treinamento. Resultados: Foram identificadas mudanças positivas nos conhecimentos, atitudes e práticas dos participantes entre o pré-teste e o pós-teste, na maioria das subdimensões avaliadas; porém, três anos depois, essas mudanças se mantiveram apenas no conhecimento sobre comportamentos suicidas e atitudes frente à prevenção. Conclusão: O programa "Abrindo Portas para a Vida" mostrou efetividade e relevância, porém, a manutenção de seus efeitos requer ações de acompanhamento e apoio a professores capacitados.

A Road Less Traveled: E-test Method for Antifungal Susceptibility Testing in Trichophyton mentagrophyte Isolates Among Patients Presenting With Dermatophytosis at a Tertiary Healthcare Center in North India.

Introduction Dermatophytosis is a common infection of the skin, hair, and nails caused by dermatophytes, a group of filamentous fungi capable of digesting and obtaining nutrients from keratin. Dermatophytes comprise three important genera: Epidermophyton, Microsporum,and Trichophyton. This study aimed to analyze the antifungal susceptibility patterns of Trichophyton mentagrophytes isolates using the epsilometer test (E-test) method. Material and methods This prospective observational study was conducted on clinically suspected cases of dermatophytosis. All samples, including skin scrapings, hair, and nails, were subjected to potassium hydroxide (KOH) examination followed by fungal culture. The Trichophyton mentagrophytes isolates were then subjected to antifungal susceptibility testing using the E-test method for the two most prescribed antifungals: itraconazole and fluconazole. Results In this study, one-third of the patients who tested positive for dermatophytosis belonged to the same family, with spouses being the most commonly affected. Tinea corporis was the most common clinical presentation, with Trichophyton mentagrophytes identified as the most common etiological agent. Itraconazole was more effective than fluconazole. Conclusion The current study demonstrated that antifungal susceptibility testing of dermatophytes using the E-test is easier and can be applied in routine laboratories as a screening method, serving as an alternative to broth microdilution.

pH-Responsive Degradable Electro-Spun Nanofibers Crosslinked via Boronic Ester Chemistry for Smart Wound Dressings.

Recent advances in the treatment of chronic wounds have focused on the development of effective strategies for cutting-edge wound dressings based on nanostructured materials, particularly biocompatible poly(vinyl alcohol) (PVA)-based electro-spun (e-spun) nanofibers. However, PVA nanofibers need to be chemically crosslinked to ensure their dimensional stability in aqueous environment and their capability to encapsulate bioactive molecules. Herein, a robust approach for the fabrication of pH-degradable e-spun PVA nanofibers crosslinked with dynamic boronic ester (BE) linkages through a coupling reaction of PVA hydroxyl groups with the boronic acid groups of a phenyl diboronic acid crosslinker is reported. This comprehensive analysis reveals the importance of the mole ratio of boronic acid to hydroxyl group for the fabrication of well-defined BE-crosslinked fibrous mats with not only dimensional stability but also the ability to retain uniform fibrous form in aqueous solutions. These nanofibers degrade in both acidic and basic conditions that mimic wound environments, leading to controlled/enhanced release of encapsulated antimicrobial drug molecules. More importantly, drug-loaded BE-crosslinked fibers show excellent antimicrobial activities against both Gram-positive and Gram-negative bacteria, suggesting that this approach of exploring dynamic BE chemistry is amenable to the development of smart wound dressings with controlled/enhanced drug release.

Incorporation of human-wildlife interactions in ecosystem-based management to enhance conservation of endangered guitarfish.

Growing human use of the marine environment increases the proximity of humans to marine wildlife and thus likely increases human-wildlife interactions. Such interactions influence perceptions of nature and promote or undermine conservation. Despite their importance, human-wildlife interactions are rarely considered in ecosystem-based marine spatial planning (MSP). Ideally, these interactions should be identified and considered in ecosystem-based management (EBM), which is often purported to be the basis for MSP. We used Marxan software and data from a citizen science project documenting location, species, age, sex, and activity type to identify regions along Israel's coast with a high probability of encounters between people and 2 species of guitarfish. We considered the geographic distribution of these encounters and the various activities undertaken by the reporting observers. We ran 4 scenarios in Marxan. Two had conservation goals of 30% and 50% guitarfish habitat protection. In the third and fourth scenarios, we added a 50% conservation goal of human leisure activities to each guitarfish conservation goal. We also conducted a gap analysis between our guitarfish conservation goals and the Israel Nature and Parks Authority's master plan for marine protected areas. We found the park authority was close to meeting the 30% goal but was far from meeting the conservation goal of 50% of guitarfish habitat conservation. Different human uses were more likely to interact with different life stages of guitarfish, and different recreational activities occurred in different areas. Identifying areas of specific human use showed which activities should be addressed in conservation management decisions. Our addition of certain recreational uses to the model of habitat conservation showed how enhancing human dimensions in conservation planning can lead to more holistic ecosystem-based conservation necessary for effective marine planning.

Incorporación de las interacciones humano­fauna dentro de la gestión basada en el ecosistema para mejorar la conservación del pez guitarra en peligro Resumen El uso creciente que el humano le da al mar incrementa la cercanía de las personas con la fauna marina, lo que probablemente incrementa las interacciones humano­fauna. Dichas interacciones influyen sobre las percepciones que se tienen de la naturaleza y promueven debilitan la conservación. A pesar de su importancia, pocas veces se consideran las relaciones humano­fauna dentro de la planeación espacial basada en ecosistemas marinos (PEM). Lo ideal debería ser la identificación y consideración de estas interacciones dentro de la gestión basada en el ecosistema (GBE), la cual con frecuencia se considera como la base de la PEM. Usamos software Marxan y datos de un proyecto de ciencia ciudadana que documenta la ubicación, especie, edad, sexo y tipo de actividad para identificar las regiones de la costa de Israel con una alta probabilidad de encuentros entre las personas y dos especies de pez guitarra. Consideramos la distribución geográfica de estos encuentros y las diferentes actividades que realizan los observadores. En Marxan corrimos cuatro escenarios. Dos de los escenarios contaban objetivos de conservación del 30% y 50% de la protección del hábitat del pez guitarra. En los otros dos escenarios, añadimos un objetivo de conservación de 50% de las actividades humanas de recreación a los objetivos uno y dos. También realizamos un análisis de brecha entre los objetivos de conservación del pez guitarra y el plan maestro para las áreas marinas protegidas de la Autoridad de Parques y Naturaleza de Israel. Descubrimos que esta autoridad estaba cerca de lograr el objetivo del 30% pero lejos del de 50% de la conservación del hábitat del pez guitarra. Fue más probable que los diferentes usos humanos interactuaran con diferentes estadios de vida del pez guitarra y las diversas actividades recreativas ocurrieron en áreas distintas. La identificación de las áreas con un uso humano específico mostró cuáles actividades deberían abordarse en las decisiones de gestión de la conservación. La suma de ciertos usos recreativos al modelo de conservación del hábitat mostró cómo aumentar las dimensiones humanas en la planeación de la conservación puede derivar en una conservación basada en el ecosistema más holística, necesaria para la planeación marina eficiente.

Recognition of online e-cigarette marketing and e-cigarette-related attitudes and behaviors among young adults.

INTRODUCTION: Past research examining the relationship between exposure to online e-cigarette marketing and e-cigarette-related attitudes and behaviors has relied on unaided recall measures that may suffer from self-report bias. To date, few studies have presented participants with e-cigarette marketing stimuli and assessed recognition. This study examined the associations between recognition of online e-cigarette marketing stimuli and e-cigarette-related attitudes and behaviors among young adults in California. METHODS: A non-probability representative sample of young adults (ages 18-24; N=1500) living in California completed an online survey assessing their recognition of online e-cigarette marketing stimuli, including image-based (i.e., Instagram, email) and audiovisual (i.e., YouTube, TikTok) promotions, and positive e-cigarette-related attitudes (e.g., appeal of e-cigarettes) and behaviors (e.g., e-cigarette use). Adjusted and weighted logistic regression analyses were used. RESULTS: 79.0% (n=1185) of young adults, including 78.1% (n=310/397) of participants under 21 years old, recognized online e-cigarette marketing. Participants who reported recognition of stimuli, compared with those who did not, had greater odds of reporting appeal of e-cigarettes (AOR=2.26, 95% CI=1.65-3.09) and e-cigarette purchase intentions (AOR=1.66, 95% CI=1.13-2.43) among all participants, and susceptibility to use e-cigarettes among never users (AOR=2.29, 95% CI=1.59-3.29). CONCLUSIONS: Young adults in California recognized audiovisual and image-based online e-cigarette marketing. Such recognition may lead to positive e-cigarette-related attitudes and behavioral intentions, especially among never users. Future research should examine the causal relationship between the associations found in this study. Findings may inform the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures. IMPLICATIONS: Recognition of online e-cigarette marketing stimuli was associated with greater odds of reporting appeal and benefits of e-cigarettes, purchase intentions, and lifetime e-cigarette use among all participants, and susceptibility to use e-cigarettes among never users. These findings may motivate the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures.

Blended e-learning and certification for medicines development professionals: results of a 7-year collaboration between King's College, London and the GMDP Academy, New York.

Introduction: The field of Medicines Development faces a continuous need for educational evolution to match the interdisciplinary and global nature of the pharmaceutical industry. This paper discusses the outcomes of a 7-year collaboration between King's College London and the Global Medicines Development Professionals (GMDP) Academy, which aimed to address this need through a blended e-learning program. Methods: The collaboration developed a comprehensive curriculum based on the PharmaTrain syllabus, delivered through a combination of asynchronous and synchronous e-learning methods. The program targeted a diverse range of professionals serving in areas related to Medical Affairs. Results: Over seven annual cohorts, 682 participants from eighty-six countries were enrolled in the program. The program's effectiveness was assessed using Kirkpatrick's model, showing elevated levels of satisfaction (over 4.0 on a five-point scale), suggesting significant gains in competence at the cognitive level and leveraged performance. Notably, 70% of responding alumni reported significant improvement in their functions, corroborated by 30% of their supervisors. The further long-term impact of the program on their respective organization has not been established. Discussion: The GMDP Academy's program has significantly contributed to life-long learning in Medicines Development, addressing educational gaps and fostering interdisciplinary collaboration. Its success highlights the importance of continuous education in keeping pace with the industry's evolving demands and underscores the potential of blended learning in achieving educational objectives in pharmaceutical medicine.

Development of triplex assay for simultaneous detection of Escherichia coli, methicillin resistant and sensitive Staphylococcus aureus in raw pork samples of retail markets.

Escherichia coli and Staphylococcus aureus are the most important food borne pathogen transmitting from animal meat and meat products. Therefore, it is vital to design an accurate and specific diagnostic tool for identifying those food-borne pathogens in animal meat and meat products. In the current study, E. coli, methicillin-resistant and sensitive S. aureus (MRSA and MSSA) were simultaneously detected using a developed triplex PCR-based technique. To obtain an optimal reaction parameter, the multiplex assay was optimised by changing just one parameter while holding the others constant. Specificity of the assay was assessed using several porcine bacterial template DNA. The plasmid DNA was used to test the multiplex PCR assay's sensitivity and interference in spiked pork samples. E. coli, MRSA, and MSSA each have PCR amplified products with sizes of 335, 533, and 209 bp, respectively. The assay detects a minimum microbial load of 102 CFU/µl for all the three pathogens and can identify bacterial DNA as low as 10-2 ng/µl. The assay was validated employing 210 pork samples obtained from retail meat shops and slaughter houses, with MRSA, E. coli, and MSSA with the occurrence rate of 1.9%, 42.38%, and 18.1%, respectively. The rate of mixed bacterial contamination in pork meat samples examined with the developed method was 6.19%, 1.43%, 1.90%, and 1.43% for MSSA & E. coli, MRSA & E. coli, MSSA & MRSA, and E. coli, MSSA & MRSA, respectively. The developed multiplex PCR assay is quick and efficient, and it can distinguish between different bacterial pathogens in a single reaction tube.

An optimal promoter regulating cytokine transgene expression is crucial for safe and effective oncolytic virus immunotherapy.

In general, ensuring safety is the top priority of a new modality. Although oncolytic virus armed with an immune stimulatory transgene (OVI) showed some promise, the strategic concept of simultaneously achieving maximum effectiveness and minimizing side effects has not been fully explored. We generated a variety of survivin-responsive "conditionally replicating adenoviruses that can target and treat cancer cells with multiple factors (m-CRAs)" (Surv.m-CRAs) armed with the granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene downstream of various promoters using our m-CRA platform technology. We carefully analyzed both therapeutic and adverse effects of them in the in vivo syngeneic Syrian hamster cancer models. Surprisingly, an intratumor injection of a conventional OVI, which expresses the GM-CSF gene under the constitutively and strongly active "cytomegalovirus enhancer and ß-actin promoter", provoked systemic and lethal GM-CSF circulation and shortened overall survival (OS). In contrast, a new conceptual type of OVI, which expressed GM-CSF under the cancer-predominant and mildly active E2F promoter or the moderately active "Rous sarcoma virus long terminal repeat", not only abolished lethal adverse events but also prolonged OS and systemic anti-cancer immunity. Our study revealed a novel concept that optimal expression levels of an immune stimulatory transgene regulated by a suitable upstream promoter is crucial for achieving high safety and maximal therapeutic effects simultaneously in OVI therapy. These results pave the way for successful development of the next-generation OVI and alert researchers about possible problems with ongoing clinical trials.

Antibacterial activity of bacteriophage-encoded endolysins against planktonic and biofilm cells of pathogenic Escherichia coli.

This study was designed to assess the possibility of using bacteriophage-encoded endolysins for controlling planktonic and biofilm cells. The endolysins, LysEP114 and LysEP135, were obtained from plasmid vectors containing the endolysin genes derived from Escherichia coli phages. The high identity (>96%) was observed between LysEP114 and LysEP135. LysEP114 and LysEP135 were characterized by pH, thermal, and lactic acid stability, lytic spectrum, antibacterial activity, and biofilm eradication. The molecular masses of LysEP114 and LysEP135 were 18.2 kDa, identified as muramidases. LysEP114 and LysEP135 showed high lytic activity against the outer membrane-permeabilized E. coli KCCM 40405 at below 37°C, between pH 5 to 11, and below 70 mM of lactic acid. LysEP114 and LysEP135 showed the broad rang of lytic activity against E. coli KACC 10115, S. Typhimurium KCCM 40253, S. Typhimurium CCARM 8009, tetracycline-resistant S. Typhimurium, polymyxin B-resistant S. Typhimurium, chloramphenicol-resistant S. Typhimurium, K. pneumoniae ATCC 23357, K. pneumoniae CCARM 10237, and Shigella boydii KACC 10792. LysEP114 and LysEP135 effectively reduced the numbers of planktonic E. coli KCCM by 1.7 and 2.1 log, respectively, when treated with 50 mM lactic acid. The numbers of biofilm cells were reduced from 7.3 to 4.1 log CFU/ml and 2.2 log CFU/ml, respectively, when treated with LysEP114- and LysEP135 in the presence of 50 mM lactic acid. The results suggest that the endolysins in combination with lactic acid could be potential alternative therapeutic agents for controlling planktonic and biofilm cells.

Detection of influenza A(H3N2) viruses with polymerase acidic subunit substitutions after and prior to baloxavir marboxil treatment during the 2022-2023 influenza season in Japan.

Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022-2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n=234), with a minor circulation of A(H1N1)pdm09 (n=10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23K/G, or I38M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6 to 100 %), a polymorphism and a mixture of PA/E23K/G, and I38M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7-14 years, with a median fever duration of 16.7 hours and a median symptom duration of 93.7 hours, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza.

Urgent action needed: addressing the regulatory gap in e-cigarette trade and usage.

Tobacco use is associated with serious health problems. Global efforts, such as the World Health Organization's Framework for Tobacco Control, have reduced tobacco use, but challenges remain. Initially perceived as aids for smoking cessation, e-cigarettes have gained popularity among young people and non-smokers. Government approaches to regulating e-cigarettes range from treating them like tobacco, requiring a prescription for their use to outright bans. Although touted as a valuable alternative, evidence suggests that increased e-cigarette use carries potential direct and indirect health risks, necessitating urgent regulatory measures on a global scale. Lack of defined and uniform regulations poses substantial public health risks, compounded by marketing targeting vulnerable groups. Immediate interventions, public awareness, and research are essential to effectively control the current e-cigarette epidemic.

Bacterial exonuclease III expands its enzymatic activities on single-stranded DNA.

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

The mutual lipid-mediated effect of the transmembrane domain of SARS-CoV-2 E-protein and glycyrrhizin nicotinate derivatives on the localization in the lipid bilayer.

Glycyrrhizinic acid (GA) is one of the active substances in licorice root. It exhibits antiviral activity against various enveloped viruses, for example, SARS-CoV-2. GA derivatives are promising biologically active compounds from perspective of developing broad-spectrum antiviral agents. Given that GA nicotinate derivatives (Glycyvir) demonstrate activity against various DNA- and RNA-viruses, a search for a possible mechanism of action of these compounds is required. In the present paper, the interaction of Glycyvir with the transmembrane domain of the SARS-CoV-2 E-protein (ETM) in a model lipid membrane was investigated by NMR spectroscopy and molecular dynamics simulation. The lipid-mediated influence on localization of the SARS-CoV-2 E-protein by Glycyvir was observed. The presence of Glycyvir leads to deeper immersion of the ETM in lipid bilayer. Taking into account that E-protein plays a significant role in virus production and takes part in virion assembly and budding, the data on the effect of potential antiviral agents on ETM localization and structure in the lipid environment may provide a basis for further studies of potential coronavirus E-protein inhibitors.

EGFR-mutated lung adenocarcinoma with choroidal oligometastasis during treatment with gefitinib: a case report.

The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma, clinical Stage IIIA. Induction chemoradiation was performed followed by right upper lobectomy and lymph node dissection. Because of positive pleural effusion cytology, which was proven after surgery, the patient was diagnosed with pathological Stage IVA with EGFR L858R mutation. At 17 months after the administration of gefitinib, left choroidal metastasis appeared. Stereotactic irradiation and ruthenium small-beam radiation were effective; however, the metastatic lesion showed regrowth 7 months after these treatments. Because the patient's choroidal oligometastasis was resistant to conservative therapy, left ophthalmectomy was performed. EGFR mutations (L858R and E709K) were detected in the resected choroidal tumor. The patient continued to take gefitinib. However, a neoplastic lesion developed on the optic nerve adjacent to the resected posterior eye segment. The lesion was treated with stereotactic radiation, gefitinib was switched to afatinib 30 mg, and the patient remains alive and disease free for 11 months.