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Introdução: A realização de grupos é uma das possibilidades de atuação das equipes da Atenção Primária à Saúde. Esse tipo de intervenção possibilita o desenvolvimento de ações de cuidado que extrapolam as consultas individuais, propiciando educação em saúde, integração, troca de experiências e ampliação da rede de apoio. Ainda que não tenham necessariamente o propósito de serem terapêuticos em termos de saúde mental, apresentam-se como espaços de promoção de saúde e prevenção de agravos. O trabalho com grupos é capaz de gerar aprimoramento para todas as pessoas envolvidas ­ usuários e profissionais ­ na medida em que possibilita colocar em evidência os saberes da comunidade, abrindo a possibilidade de que as intervenções em saúde sejam criadas em coletivo. Objetivo: Analisar o processo de desenvolvimento da habilidade de facilitação de grupos e os impactos das habilidades adquiridas na sua dinâmica, bem como na sua efetividade como ferramenta de produção de saúde, considerando as habilidades e competências da Medicina de Família e Comunidade. Métodos: Trata-se de pesquisa qualitativa desenvolvida na UBS Santa Cecília. Os encontros aconteceram semanalmente pelo período de uma hora durante seis meses. A ferramenta utilizada para acompanhamento do desenvolvimento da habilidade de facilitação se deu pela observação estruturada, baseada em cinco competências básicas para facilitação de grupos. A dinâmica estabelecida consistiu na determinação de uma profissional facilitadora e outra observadora, que registrou as intervenções realizadas, sendo esses papéis invertidos a cada encontro. Quinzenalmente os dados eram analisados, gerando reflexões e sugestões para melhoria das intervenções. Resultados: Cada competência descrita na ferramenta utilizada teve como resultado o desenvolvimento de habilidades primordiais para o funcionamento do grupo. Um dos maiores indicadores do êxito em alcançar as habilidades desejadas ocorreu pela observação de intervenções cada vez menos necessárias, tomando as participantes os papéis de protagonistas e responsáveis pelo desenvolvimento do grupo, questionando, produzindo e obtendo saúde. Conclusões: A utilização de um instrumento de observação e reflexão das competências do agente atuante como facilitador de um grupo permitiu que a dinâmica se estabelecesse de forma fluida com rápido entendimento das participantes sobre seus papéis no contexto geral do grupo. Observou-se também que a relação estabelecida entre elas resultou na formação de rede de apoio, melhoria do autocuidado e conhecimento, informação em saúde e apoio social às envolvidas.

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Introduction: Running support groups is one of the actions of Primary Health Care teams. This type of intervention enables the development of actions that go beyond individual consultations as the only space of care, providing health education, integration, exchange of experiences, and an enlargement in the support network. Although these groups do not necessarily have the purpose of being therapeutic in terms of mental health, they are presented as spaces for building health promotion and disease prevention. The alternative of groups as care practice generates improvement for all involved individuals ­ users and professionals ­ as it makes it possible to highlight the community's knowledge, opening the possibility that health interventions are created collectively. Objective: To analyze the process of ability development in regards to the facilitation of support groups and the impacts of the acquired skills on its dynamics, as well as on its effectiveness as a health production tool, considering the skills and competencies in Family and Community Medicine. Methods: Qualitative study developed at Santa Cecilia BHU. The meetings took place for one hour weekly over a six months period and the tool used to monitor the development of the facilitation skill was the instrument "Structured Observation", based on five basic skills for facilitating groups. The dynamics consisted of the determination of a professional facilitator and an observer, who recorded the interventions that were carried out, with these roles being reversed at each meeting. The data were analyzed bi-weekly, with reflections and suggestions for improving interventions. Results: Each competence described in the tool resulted in the development of essential skills for the functioning of the group. One of the major indicators of the achievement of the desired skills occurred by observing interventions that were less and less necessary, with participants taking on the roles of protagonists and becoming responsible for the development of the group, questioning, producing, and acquiring health. Conclusions: The use of an instrument for observing and reflecting on the skills of the agent acting as a group facilitator allows the dynamics to be fluidly established, with a quick understanding of the participants about their roles in the general context of the group. It was also observed that the relationship established between them resulted in the formation of a support network, improvement of self-care and knowledge, health information and social support for those involved.

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Introducción: La realización de grupos es una de las acciones de los equipos de la Atención Primaria a la Salud. Este tipo de intervención hace posible el desarrollo de acciones que extrapolan las consultas individuales como único espacio de cuidado, ofreciendo educación en salud, integración, intercambio de experiencias y ampliación de la red de apoyo. Aunque estos grupos no tengan necesariamente el propósito de ser terapéutico en términos de salud mental, se presentan como sitios de construcción de promoción de salud y prevención de agravios. La alternativa de los grupos como una práctica asistencial crea una mejora para todas las personas involucradas ­ usuarios y profesionales ­ ya que habilita colocar en evidencia los saberes de la comunidad, abriendo la posibilidad de que las intervenciones en salud sean creadas en colectivo. Objetivo: Analizar el proceso de desarrollo de la habilidad de facilitación de grupos y los impactos de las habilidades adquiridas en la dinámica de este, así como en la efectividad como herramienta de producción de salud, considerando las habilidades y competencias de la Medicina de Familia y Comunidad. Métodos: Se trata de estudio cualitativo llevado a cabo en la UBS Santa Cecília. Los encuentros ocurrieron semanalmente durante una hora por seis meses y la herramienta utilizada para seguimiento del desarrollo de la habilidad de facilitación fue el instrumento Observación Estructurada, basado en cinco competencias básicas para facilitación de grupos. La dinámica establecida consistió en la determinación de una profesional facilitadora y otra observadora, que registró las intervenciones realizadas, siendo esos papeles cambiados a cada encuentro. A cada quince días los datos eran analizados, haciendo reflexiones y sugestiones para mejorar las intervenciones. Resultados: Cada competencia descrita en la herramienta utilizada tuvo como resultado el desarrollo de habilidades primordiales para el funcionamiento del grupo. Uno de los grandes indicadores del éxito en alcanzar las habilidades deseadas ocurrió por la observación de intervenciones cada vez menos necesarias, tomando las participantes los papeles de protagonistas y responsables por el desarrollo del grupo, cuestionando, produciendo y obteniendo salud. Conclusiones: La utilización de un instrumento de observación y reflexión de las competencias del agente actuante como facilitador de un grupo permiten que la dinámica se establezca de forma fluida con rápido entendimiento de las participantes sobre sus papeles en el contexto general del grupo. Se pudo observar también que la relación establecida entre ellas resultó en la formación de red de apoyo, mejora del autocuidado y conocimiento, información en salud y apoyo social a las involucradas.

Assuntos

Humanos , Feminino , Atenção Primária à Saúde , Mulheres , Educação em Saúde , Participação da Comunidade , Prática de Grupo

RESUMO

Nanoparticles play a crucial role in the field of nanotechnology, offering different properties due to their surface area attributed to their small size. Among them, silver nanoparticles (AgNPs) have attracted significant attention due to their antimicrobial properties, with applications that date back from ancient medicinal practices to contemporary commercial products containing ions or silver nanoparticles. AgNPs possess broad-spectrum biocidal potential against bacteria, fungi, viruses, and Mycobacterium, in addition to exhibiting synergistic effects when combined with certain antibiotics. The mechanisms underlying its antimicrobial action include the generation of oxygen-reactive species, damage to DNA, rupture of bacterial cell membranes and inhibition of protein synthesis. Recent studies have highlighted the effectiveness of AgNPs against various clinically relevant bacterial strains through their potential to combat antibiotic-resistant pathogens. This review investigates the proteomic mechanisms by which AgNPs exert their antimicrobial effects, with a special focus on their activity against planktonic bacteria and in biofilms. Furthermore, it discusses the biomedical applications of AgNPs and their potential non-preparation of antibiotic formulations, also addressing the issue of resistance to antibiotics.

RESUMO

Lynching remains a common form of collective punishment for alleged wrongdoers in Latin America, Africa, and Asia today. Unlike other kinds of collective violence, lynching is usually not carried out by standing organizations. How do lynch mobs overcome the high barriers to violent collective action? I argue that they draw on local community ties to compensate for a lack of centralized organization. Lynch mobs benefit from solidarity and peer pressure, which facilitate collective action. The study focuses on Mexico, where lynching is prevalent and often amounts to the collective beating of thieves. Based on original survey data from Mexico City and a novel lynching event dataset covering the whole of Mexico, I find that individuals with more ties in their communities participate more often in lynching, and municipalities with more highly integrated communities have higher lynching rates. As community ties and lynching may be endogenously related, I also examine the posited mechanisms and the causal direction. Findings reveal that municipalities exposed to a recent major earthquake-an event that tends to increase community ties-subsequently experienced increased levels of lynching. Importantly, I find that interpersonal trust is unrelated to lynching, thus showing that different aspects of social capital have diverging consequences for collective violence, with community ties revealing a "dark side."

RESUMO

OBJECTIVES: Despite cervical cancer (CC) being a preventable disease, its incidence remains high in marginalized communities due to inequalities that restrict access to health services. This article investigates the experiences, perceptions, and attitudes regarding the screening of indigenous women in a region of the Colombian Amazon during a cervical cancer prevention initiative facilitated by community participation. DESIGN: Qualitative study based on interviews conducted with women and indigenous leaders from Paujil reserve. They participated in research focused on cervical cancer prevention, which employed a methodology of collaboration between academia and communities aimed at enhancing women's health and reducing inequalities in access to healthcare services. The analysis utilized a deductive and inductive approach. RESULTS: Five main themes were addressed: 'Barriers within health services'; 'Individual and cultural constraints'; 'Motivations and facilitators'; 'Positive experiences within the research framework'; and 'Suggestions for encouraging women's participation.' Challenges related to appointment scheduling and result delivery were frequently cited as obstacles to access. Misinformation, feelings of shame, fear, and distrust towards health services played significant roles in the reluctance to undergo screening. Factors such as support from family and community networks, respectful treatment, ease of scheduling appointments, the presence of female healthcare professionals, and involvement of leaders fluent in indigenous languages were identified as positive facilitators of screening acceptance. CONCLUSION: Understanding the factors that influence access to screening is crucial for reducing inequalities in service delivery for indigenous women. The involvement of trained leaders who can identify these factors and motivate women can have a positive impact on the acceptance and guidance of cervical cancer prevention programs.

RESUMO

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.

Assuntos

Antibacterianos , Proteínas de Bactérias , Permeabilidade da Membrana Celular , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Tiazinas/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética

RESUMO

The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.

Assuntos

Estimulação Acústica , Audiometria de Resposta Evocada , Vias Auditivas , Chinchila , Nervo Coclear , Estimulação Luminosa , Vigília , Tecnologia sem Fio , Animais , Nervo Coclear/fisiologia , Vigília/fisiologia , Tecnologia sem Fio/instrumentação , Vias Auditivas/fisiologia , Audiometria de Resposta Evocada/métodos , Modelos Animais , Percepção Auditiva/fisiologia , Cóclea/fisiologia , Percepção Visual , Fatores de Tempo

Assuntos

Antineoplásicos , Complexos de Coordenação , Neoplasias , Elementos de Transição , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Elementos de Transição/química , Neoplasias/tratamento farmacológico

RESUMO

Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.

Assuntos

Derivados de Alilbenzenos , Anisóis , Diabetes Mellitus Experimental , Estresse Oxidativo , Nervo Isquiático , Animais , Derivados de Alilbenzenos/farmacologia , Nervo Isquiático/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Anisóis/farmacologia , Anisóis/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/metabolismo , Potenciais de Ação/efeitos dos fármacos , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico

RESUMO

Given the multiple challenges that agriculture faces, collective action is a potential pathway towards more sustainable agriculture. This article aims to contribute to the literature by assessing the extent to which collective action can meet the objective of both healthy and profitable production in the French West Indies. To do so, we call on the theory of collective action and emphasise the role of formal and informal collectives in achieving the objectives of improving income and implementing agroecological practices. We use original data collected in 2022 from 409 vegetable farmers in Martinique and Guadeloupe. We consider the interdependence between farmers' economic and environmental objectives through a simultaneous equations model. We characterise the diversity of collectives according to their degree of formalisation and to the adequacy between the objectives pursued by these collectives and the individual objectives of their members. Our results show that the achievement of an individual objective is fostered by its adequacy with the objective set by the collective and also, to a certain extent, by the degree of formalisation of this collective. It appears that achieving individual objectives is based on sharing common objectives as well as having collective rules. More particularly, we find that producer organisations - collectives considered to be the most formal - best meet the objectives of improving income and adopting agroecological practices. However, in the French West Indies, the instability of such collectives and the organisational deficiencies of the sector call into question their real long-term impact. These findings contribute to a better understanding of farmers' decision-making and provide relevant policy implications for supporting agricultural collectives in managing and federating producers towards achieving a more healthy and profitable production.

Assuntos

Agricultura , Fazendeiros , Verduras , Índias Ocidentais , Conservação dos Recursos Naturais , Martinica , Humanos , Guadalupe

RESUMO

Objective: This study aimed to the effects of the Health Action Process Approach (HAPA) in promoting the quality of nurses' communication skills among nurses. Methods: The present quasi-experimental research was conducted on 148 nurses (76 in the intervention and 72 in the control group) in Yazd province (Iran). In this study, the total number of nurses in one hospital was selected as the intervention group, while the nurses from another hospital were chosen as the control group. The participants were recruited from public hospitals in Ardakan and Meibod cities. The data collection instrument was a questionnaire based on the Health Action Process Approach (HAPA) Constructs and a communicative skill questionnaire. The data were collected from the two groups before, one month after, and four months after the intervention. The control group did not receive any educational training during the course of the study. Results: In the pretest, no statistically significant difference was found between the intervention and control groups regarding the behavioral stages of effective communication with patients. In the posttest, the mean task self-efficacy score was significantly increased in the intervention group compared to the control (p<0.001). The mean coping self-efficacy score was also significantly higher in the intervention group than the control in the posttest (p<0.001). Moreover, the mean coping planning score was significantly increased in the post-test intervention group(p < 0.001). The mean communicative skill score was also significantly increased in the intervention group compared to the post-test control (p=0.03). Conclusion: The intervention used in the present study based on the target model (HAPA) significantly affected nurses' self-efficacy and communicative skills in the experimental group.

Assuntos

Comunicação , Autoeficácia , Humanos , Irã (Geográfico) , Adulto , Inquéritos e Questionários , Feminino , Masculino , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/educação , Adaptação Psicológica , Competência Clínica , Adulto Jovem , Pessoa de Meia-Idade

RESUMO

Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.

Assuntos

Antivirais , Febre de Chikungunya , Vírus Chikungunya , Tirosina , Replicação Viral , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/fisiologia , Tirosina/farmacologia , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/química , Antivirais/farmacologia , Antivirais/química , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Animais , Replicação Viral/efeitos dos fármacos , Chlorocebus aethiops , Células Vero , Humanos , Internalização do Vírus/efeitos dos fármacos , Proteínas Virais/metabolismo

RESUMO

Metallocompounds are a class of anticancer compounds largely used in the treatment of several types of solid tumors, including bone cancer. Osteosarcoma (OS) is a primary malignant bone tumor that frequently affects children, adolescents and young adults. It is a very invasive type of tumor, so ∼40% of patients develop distant metastases, showing elevated mortality rates. In this review, we present an outline of the chemistry and antitumor properties of metal-based compounds in preclinical (in vitro and in vivo) and clinical OS models, focusing on the relationship between structure-activity, molecular targets and the study of the mechanism of action involved in metallocompound anticancer activity.

Assuntos

Antineoplásicos , Neoplasias Ósseas , Osteossarcoma , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Animais , Relação Estrutura-Atividade , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/química

RESUMO

Retinoblastoma protein is central in signaling networks of fundamental cell decisions such as proliferation and differentiation in all metazoans and cancer development. Immunostaining and biochemical evidence demonstrated that during interphase retinoblastoma protein is in the nucleus and is hypophosphorylated, and during mitosis is in the cytoplasm and is hyperphosphorylated. The purpose of this study was to visualize in vivo in a non-diseased tissue, the dynamic spatial and temporal nuclear exit toward the cytoplasm of this protein during mitosis and its return to the nucleus to obtain insights into its potential cytosolic functions. Using high-resolution time-lapse images from confocal microscopy, we tracked in vivo the ortholog in plants the RETINOBLASTOMA RELATED (RBR) protein tagged with Green Fluorescent Protein (GFP) in Arabidopsis thaliana's root. RBR protein exits from dense aggregates in the nucleus before chromosomes are in prophase in less than 2 min, spreading outwards as smaller particles projected throughout the cytosol during mitosis like a diffusive yet controlled event until telophase, when the daughter's nuclei form; RBR returns to the nuclei in coordination with decondensing chromosomal DNA forming new aggregates again in punctuated larger structures in each corresponding nuclei. We propose RBR diffused particles in the cytoplasm may function as a cytosolic sensor of incoming signals, thus coordinating re-aggregation with DNA is a mechanism by which any new incoming signals encountered by RBR may lead to a reconfiguration of the nuclear transcriptomic context. The small RBR diffused particles in the cytoplasm may preserve topologic-like properties allowing them to aggregate and restore their nuclear location, they may also be part of transient cytoplasmic storage of the cellular pre-mitotic transcriptional context, that once inside the nuclei may execute both the pre mitosis transcriptional context as well as new transcriptional instructions.

RESUMO

Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as Dengue, Chikungunya and Zika, causing a major impact on global economic and public health. The main way to prevent these diseases is vector control, which is carried out through physical and biological methods, in addition to environmental management. Although chemical insecticides are the most effective strategy, they present some problems such as vector resistance and ecotoxicity. Recent research highlights the potential of the imidazolium salt "1-methyl-3-octadecylimidazolium chloride" (C18MImCl) as an innovative and environmentally friendly solution against Ae. aegypti. Despite its promising larvicidal activity, the mode of action of C18MImCl in mosquito cells and tissues remains unknown. This study aimed to investigate its impacts on Ae. aegypti larvae and three cell lines of Ae. aegypti and Ae. albopictus, comparing the cellular effects with those on human cells. Cell viability assays and histopathological analyses of treated larvae were conducted. Results revealed the imidazolium salt's high selectivity (> 254) for mosquito cells over human cells. After salt ingestion, the mechanism of larval death involves toxic effects on midgut cells. This research marks the first description of an imidazolium salt's action on mosquito cells and midgut tissues, showcasing its potential for the development of a selective and sustainable strategy for vector control.

Assuntos

Aedes , Imidazóis , Inseticidas , Larva , Aedes/efeitos dos fármacos , Animais , Larva/efeitos dos fármacos , Imidazóis/toxicidade , Imidazóis/farmacologia , Inseticidas/toxicidade , Inseticidas/farmacologia , Humanos , Mosquitos Vetores/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Controle de Mosquitos/métodos

RESUMO

Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that "all short carbon chain acids … are likely reproductive and developmental toxicants". This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.

Assuntos

Ácidos Carboxílicos , Ácidos Carboxílicos/toxicidade , Ácidos Carboxílicos/química , Animais , Ratos , Testes de Toxicidade/métodos , Humanos

RESUMO

Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

Assuntos

Antifúngicos , Candida , Complexos de Coordenação , Cobre , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Fenantrolinas , Teofilina , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Fenantrolinas/farmacologia , Fenantrolinas/química , Candida/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Teofilina/farmacologia , Teofilina/química , Espécies Reativas de Oxigênio/metabolismo , Humanos

RESUMO

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Assuntos

Gânglios da Base , Percepção do Tempo , Gânglios da Base/fisiologia , Animais , Humanos , Percepção do Tempo/fisiologia , Neurônios/fisiologia , Sensação/fisiologia

RESUMO

The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The "canonical" mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed. This review gathers most of the "non-canonical" notions on antibiotics and resistance: from the alternative mechanisms of action of antibiotics and the limitations of susceptibility testing to the wide variety of selective pressures, lateral gene transfer mechanisms, ubiquity, and societal factors maintaining resistance. Only by having a "big picture" view of the problem can adequate strategies to harness resistance be devised. These strategies must be global, addressing the many aspects that drive the increasing prevalence of resistant bacteria aside from the clinical use of antibiotics.

RESUMO

This study evaluated the chemical profile, antimicrobial activity, and the presence of potentially toxic elements in geopropolis extracts produced by Melipona scutellaris in the Recôncavo region of Bahia, Brazil. It was found that the major chemical compounds belong to the class of phenolic compounds, with emphasis on the presence of gallic acid. In this study, no potentially toxic elements were found in the analysed geopropolis. Regarding the antimicrobial potential, gram-positive bacteria were susceptible to the action of geopropolis extract at concentrations of 0.25 to 2.5 mg.mL-1, highlighting its microbiological activity against Streptococcus mitis (ATCC 00456) and Candida albicans (CCMB 251). Thus, this geopropolis extract can be used as a bacteriostatic rather than a bactericide. Our results suggest the potential for the economic and therapeutic use of M. scutellaris geopropolis, adding value to one of the meliponiculture products.