Inspiratory Muscle Training in Phase 1 and 2 Postoperative Cardiac Rehabilitation Following Coronary Artery Bypass Graft Surgery: Systematic Review with Meta-Analysis.

OBJECTIVE: This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. METHODS: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. RESULTS: Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (-1.02 days; 95% CI = -2.00 to -0.03) and increased exercise capacity (6-minute walk distance [6MWD]).(+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6MWD (45.84 m; 95% CI = 10.89 to 80.80), MIP (-23.19 cm H2O; 95% CI = -31.31 to -15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (-11.17; 95% CI = -17.98 to -4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. CONCLUSIONS: IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. IMPACT: IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits.

Homossexualidade, família e religião: uma análise psicossocial de orações para Bobby / Homosexualidad, familia y religión: un análisis psicosocial de oraciones por Bobby / Homosexuality, family and religion: a psychosocial analysis of prayers for Bobby

RESUMO Discute-se a relação entre homossexualidade, religião e família, a partir da Psicologia Sócio-histórica. Busca-se investigar, por meio de uma análise fílmica, os sentidos e significados apresentados pela família, em relação à homossexualidade. Para tanto, utiliza-se a produção filmográfica Orações para Bobby, como um documento cultural, datado historicamente, que permite evidenciar as formas de vivências psicossociais. Nesta proposição, metodologicamente são adotados procedimentos de identificação, recorte, descrição e interpretação de cenas emblemáticas. Desse modo, realizaram-se a identificação, o recorte e a localização temporal, a descrição detalhada de textos das cenas com seus aspectos visuais e auditivos e construíram-se três categorias de análise das 16 cenas emblemáticas selecionadas: significados de religião, homossexualidade e família; significado de homossexualidade e suicídio; e impactos intergeracionais do signo da homossexualidade. Os resultados indicam que a relação entre a homossexualidade assumida, dogmas religiosos e família tradicional podem desencadear atos suicidas com motivação volitiva e consciente; as acepções de signo, sentidos, significado, mediação e internalização contribuíram para compreender o impacto que os conceitos da homossexualidade, socialmente construídos, incidem na vivência da sexualidade de jovens homossexuais e seus relacionamentos afetivos no âmbito social e familiar. O significado da homossexualidade apresenta-se de forma pejorativa, com força de materialidade histórica e de manutenção hegemônica de ideias, por meio de grupos conservadores, que encontram na família um lugar afetuoso e subjetivo, de reprodução fértil, ao passo que coletivos identitários, como a comunidade LGBTQIA+, buscam espaços para o debate político com avanços e rupturas dessas noções, historicamente construídas, no processo de significação da sexualidade.

RESUMEN. Se discute la relación entre la homosexualidad, religión y familia, establecido em la psicologia sociohistórica. Busca indagar, a través de un análisis fílmico, los sentidos y significados presentados por la familia, en relación a la homosexualidad. Para esto, se usa la producción cinematográfica, Oraciones por Bobby como documento histórico y cultural que permite ressaltar las formas de las experiencias psicosociales. En esta proposición se adoptan metodologicamente procedimientos de identificación, recorte, descripción e interpretación de escenas emblemáticas. De este modo, se cosntruyeron tres categorías de análisis de las 16 escenas emblemáticas seleccionadas: significados de religión, homosexualidad y familia; significado de homosexualidad y suicido y los impactos intereracionales de los signos de la homosexualidad. Los resultados indican que larelación entre la homosexualidad asumida, los dogmas religiosos y la familia tradicional puede desencadenar actos suicidas com motivación volitiva y consciente; los significados del signo, los sentidos, el significado, la mediación y la internalización contribuyeron a la comprensióndel impacto que los conceptos de homosexualidad, construidos socialmente, tienen en la experiencia de la sexualidad de los jóvenes homosexuales y sus relaciones afectivas en la esfera social y familiar. Finalmente, se considera que la producción cinematográfica anima las discusiones sobre temas y fenómenos complejos, conorígenes históricas y representaciones persistentes, en el cualmoviliza nuevas formas de pensar y construir lo social; el significado de la homosexualidad se presenta de manera peyorativa , com lafuerza de la materialidade histórica y el mantenimiento hegemónico de las ideas, a través de grupos conservadores, que encuentran en la família un lugar, cariñoso y subjetivo, de reproducción fértil, mientras que los colectivos de identidad, la comunidad LGBTQIA+ busca espacios para el debate político y los avances y rupturas de estas nociones, historicamente construidas, en el processo de significar la sexualidad. Se insertan nuevos componentes, a través de las historias de personas que intercambian visiones y palabras impregnadas de sentido, que se reformulan constantemente.

ABSTRACT The relationship among homosexuality, religion and family is discussed, based on Socio-historical Psychology. For this purpose, the movie Prayers for Bobby is used as a cultural document, historically dated, which allows highlighting the forms of psychosocial experiences. Three categories of analysis of the 16 selected emblematic scenes were constructed: meanings of religion, homosexuality and family; the meaning of homosexuality and suicide; and intergenerational impacts of the homosexuality sign. The results indicate that the relationship among assumed homosexuality, religious dogma and the traditional family can trigger suicidal acts with volitional and conscious motivation; the sign, senses, meaning, mediation and internalization approaches have contributed to understanding the impact that socially constructed concepts of homosexuality have on the experience of young homosexuals sexuality and their affective relationships in the social and family spheres. Finally, it is considered that cinematographic production encourages discussions of complex issues and phenomena with persistent origins and historical representations, which mobilize new ways of thinking and constructing society. Homosexual meaning is set out pejoratively, with the strength of historical materiality and hegemonic maintenance of ideas, through conservative groups, who find an affectionate and subjective, fertile reproduction place in the family. In contrast, identity collectives, the LGBTQIA+ community, seek spaces for political debate and advances and ruptures of historically constructed notions in the process of signifying sexuality. The individuals' stories exchanging visions and words are inserted with new components constantly reformulated with meaning.

Endoparasites in domestic cats (Felis catus) in the semi-arid region of Northeast Brazil.

The aim of this study was to evaluate the prevalence of endoparasites in domestic cats (Felis catus) in the city of Sousa, state of Paraíba, Northeast Brazil. A total of 207 samples of fresh feces were randomly collected from domestic and semi-domiciled cats. The samples were analyzed by simple centrifugation and centrifuge-flotation in sucrose solution for the diagnosis of helminth eggs and enteric protozoan oocysts and cysts. Epidemiological information was obtained to determine risk factors related to infections. Among the samples collected, 81.6% (169/207; 95% CI: 77.4-83.8) were positive for at least one parasite genus. Ancylostoma spp. was the most prevalent, at 67.1% (139/207), followed by Taenia spp. at 28.5% (59/207), and Spirometra spp. and Platynosomum sp., both at 17.3% (36/207). The variables associated with helminth infection were a historic lack of deworming (Odds ratio = 12.25) and the presence of dry fur (Odds ratio = 2.15). No risk factors were observed for enteric protozoa infection. This study demonstrated a high prevalence of endoparasites in domestic cats in the city of Sousa, state of Paraíba, and associated risk factors, thus establishing an overview of the main helminths and protozoa that affect cats in this region.

Vídeo educativo participativo para humanização da assistência em saúde / Participatory educational video for the humanization of health care

Comunicar más notícias envolve, além de conhecimentos, complexidades afetivas e éticas. Sensibilizar médicos utilizando um vídeo participativo sobre a comunicação de más notícias em Unidade de Terapia Intensiva Neonatal, fundamentado no SPIKES e na antropologia visual. Qualitativa, descritiva exploratória, em três etapas: 1) Diagnóstico-participação de médicos e mães; 2) Desenvolvimento-produção do vídeo; e 3) Avaliação-percepção de médicos sobre o vídeo. Foi utilizada análise de conteúdo de Bardin.A Etapa 1 indicou: ambiência inadequada, pouca preocupação com as mães, pouco suporte emocional, inadequado convite para o diálogo, linguagem e comunicação inadequadas, pouca empatia e necessidade de melhorar a humanização. Sobre o vídeo baseado na Etapa 1, a percepção dos médicos indicou: aumento do seu grau de responsabilidade, reflexão sobre suas práticas profissionais e estímulo ao aprendizado teórico e à empatia nas relações profissionais na Unidade de Terapia Intensiva. Há dificuldades no processo de comunicação de más notícias, e a utilização de vídeo educativo participativo representa importante estratégia de incentivo à humanização da assistência em saúde.

Delivering bad news involves not only knowledge, but also affective and ethical difficulties.To raise the awareness of physicians using a participatory video about delivering bad news in an Intensive Care Therapy, based on SPIKES and on visual anthropology. Qualitative, descriptive, and exploratory study in three stages: 1) Diagnosis - participation of physicians and mothers; 2) Development - video production; 3) Evaluation - perception from physicians about the video. Bardin's content analysis was used;Stage 1 showed: inadequate environment, little concern about the mothers, little emotional support, inadequate openness for dialog, inadequate language and communication, little empathy, and need to improve humanization. About the video based on Stage 1, the perception of physicians indicated: increased degree of responsibility, reflections on their professional practices, and encouragement to theoretical knowledge and to empathy in professional relations in the Intensive Care Unit. There are issues in the process of delivering bad news, and the use of educational participatory videos is an important strategy to humanize health care.

Cannabis sativa-based oils against aluminum-induced neurotoxicity.

The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer's and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.

Neurotoxicological effects of venlafaxine on Caenorhabditis elegans and Danio rerio.

The growing consumption of psychoactive drugs, such as Venlafaxine (VFX), can negatively affect the organisms. Our main hypothesis is to investigate if VFX at human-used doses could exert effects on the behavioral, nervous, and antioxidant systems of two different organisms, zebrafish and C. elegans. We evaluated the effect of acute exposure to VFX at four concentrations (0, 37.5, 75, and 150 mg L-1) using toxicological indicator assessments. We evaluated zebrafish behavior using the novel tank test (NTT), social preference test (SPT), cortisol levels, acetylcholinesterase (AChE) activity, and antioxidant system. In C. elegans, we evaluated body bends, defecation cycles, pharyngeal pumping, AChE activity, and antioxidant system. C. elegans do not show alterations in the behavior analysis of pharyngeal pumping and body bends. Instead, the defecation cycle was increased in the highest dose of VFX. AChE activity also does not have differences compared to the control, the same occurs in lipid peroxidation rates. These results showed that nematodes were more resistant to changes when exposed to VFX. Zebrafish exposed to VFX showed changes in the NTT and SPT test, mainly in the anxiolytic pattern, suggesting that VFX alters this anxiolytic-like behavior. Comparing both organisms, we can observe that zebrafish seems to be more sensitive in this neurotoxicological evaluation.

Pyrethroid-based insecticides exert transgenerational, persistent, and chronic effects in Caenorhabditis elegans.

The use of agrichemical pyrethroid-based insecticides to combat crop infestations and ectoparasites in animals is increasing. In this context, two pyrethroid-based insecticides are widely used, λ-cyhalothrin and Cypermethrin. The mechanism of action of these insecticides is characterized by the opening of ion channels and death by neural hyperexcitability. In this study, we evaluated the toxicological effect of two pyrethroid-based insecticides λ-cyhalothrin and Cypermethrin in C. elegans aiming to evaluate the transgenerational (TG), neonatal (NN) and lifespan (LS) effects of these compounds. At the end of each exposure period, were evaluated behavioral biomarkers of body bends, pharyngeal pumping, and feeding behavior. Furthermore, the fluorescent expression of antioxidant enzymes (superoxide dismutase, catalase, and glutathione-S-transferase) and the fluorescent expression of PolyQ40 aggregates were quantified. Lastly, the activity of the enzyme acetylcholinesterase (AChE) was quantified. Changes in TG were more related to changes in AChE enzyme activity that probably were transferred to the offspring, altering behavioral biomarkers in the adult life of offspring from exposed parents. However, alterations in LS were related to the modulation of ion channels in a chronic way, exerting behavioral effects. In addition, both compounds increased the expression of PolyQ40 muscle aggregates in mutant worms. These proteins are related to the increased probability of the senile incidence of Huntington's Disease in genetically predisposed patients.

Transfluthrin- and prallethrin-based insecticides elicit specific enzymatic antioxidant responses in different tissue of zebrafish.

Pyrethroids prallethrin (P-BI) and transfluthrin (T-BI) are among the most commonly used molecules with insecticide action. These molecules comprise different formulations of insecticides largely used in household, agricultural, and animal production fields. However, the increased use of these molecules has led to concerns regarding their safety in animals and humans. Oxidative stress (OS) is believed to be easily established by xenobiotic contacts, such as pyrethroids. We aimed to evaluate and understand the impact of two household insecticides and two doses applied to different tissues of the antioxidant system of zebrafish (Danio rerio). We observed that the effect on the antioxidant system differed between tissues. The muscle was the most affected tissue in the body, the antioxidant enzymes were activated, and a mechanism of non-enzymatic antioxidants was activated; however, it could still cause cellular damage. The observed effect on muscle may be related to the progression of neurodegenerative conditions. In addition, in the brain, these compounds can inactivate the first line of enzymatic antioxidant defense, which is compensated for by the second line, avoiding cellular damage. Ultimately, the gill tissue did not appear to suffer lipid damage, but heme group formation was largely affected by the compounds.

Household based-pyrethroids on adult zebrafish (Danio rerio) exert behavioral and cholinergic changes in different brain regions.

Pyrethroid-based insecticides are largely used for mosquito control. These compounds have household and agricultural applications with different formulations. Two important compounds used as household insecticides are prallethrin and transfluthrin, both from the pyrethroid chemical group. With the mode of action centered on sodium channels, pyrethroids keep the ionic sodium channels open for a long time causing the death of the insect by nervous hyperexcitability. Given the increased use of household insecticides by humans and the incidence of disease outbreaks with unknown etiology such as autism spectrum disease, schizophrenia, and Parkinson's disease we investigate some physiological inputs of these compounds on zebrafish. In this study, we evaluated the social interaction, shoaling formation, and anxiety-like behavior of zebrafish exposed chronically to transfluthrin- and prallthrin-based insecticides (T-BI and P-BI). In addition, we quantified the activity of the enzyme acetylcholinesterase (AChE) in different brain regions. We observed that both compounds caused anxiolytic behavior and reduced shoaling formation and social interaction. Their behavioral biomarkers indicated a harmful ecological effect on the specie as well as a possible impact of these compounds on autism spectrum disorder (ASD) and schizophrenia (SZP). In addition, the AChE activity would change its activity in different brain regions modulating the anxiety-like behavior and social behavior in zebrafish. We conclude that P-BI and T-BI make us alert about the relationship of these compounds with nervous diseases related to cholinergic signaling.

The effect of volunteer-led activities on the quality of life of volunteers, residents, and employees of a long-term care institution: a cohort study.

BACKGROUND: The COVID-19 pandemic primarily impacted long-term care facilities by restricting visiting and circulation of visitors, affecting the quality of life (QoL) of older adults living in these institutions. Volunteer activities, essential for older adults' daily life, were also interrupted and potentially negatively impacted the QoL of older adults, volunteers themselves, and also employees in these institutions. In this context, this study aims to evaluate the impact of the return of volunteer-led activities in a long-term care institution on the QoL of older adult residents, employees, and volunteers. METHODS: This study used a pre-test and post-test design within the same group. The first round of data collection was conducted before volunteer-led activities returned and the second round after 1 month of return. The instrument used to assess QoL was the EUROHIS-QoL-8 scale. This study was conducted within a nursing home in São Paulo, Brazil, created in 1937 by members of the Israeli community living in Brazil. Volunteer-led activities were part of residents' daily life before the COVID-19 pandemic, when these activities were interrupted for about 20 months. A total of 79 individuals participated in both rounds (pre and post), of which: 29 residents, 27 volunteers, and 23 employees of the long-term care institution. RESULTS: Using a Wilcoxon signed-rank test, the analyses indicated improvements after the 1 month return in different QoL aspects for the three groups. Volunteers improved their personal relationships (Z - 2.332, p < .05), residents their overall health (Z - 2.409, p < .05) and employees in their overall QoL perception (Z - 2.714, p < .05). Influencing factors for residents were the number of activities (3 or more), gender (male), and education (undergraduate/graduate). For employees, those who assumed additional activities due to the volunteer-led activities interruption had a significant impact on their overall QoL. CONCLUSIONS: Evidence from this study suggests that volunteers' return positively impacted different QoL aspects for volunteers, residents, and employees.

Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer.

The frequent activation of the PI3K/AKT/mTOR pathway and its crucial role in estrogen receptor-positive (ER+) breast cancer tumorigenesis and drug resistance has made it a highly attractive therapeutic target in this breast cancer subtype. Consequently, the number of new inhibitors in clinical development targeting this pathway has drastically increased. Among these, the PIK3CA isoform-specific inhibitor alpelisib and the pan-AKT inhibitor capivasertib were recently approved in combination with the estrogen receptor degrader fulvestrant for the treatment of ER+ advanced breast cancer after progression on an aromatase inhibitor. Nevertheless, the clinical development of multiple inhibitors of the PI3K/AKT/mTOR pathway, in parallel with the incorporation of CDK4/6 inhibitors into the standard of care treatment in ER+ advanced breast cancer, has led to a multitude of available therapeutic agents and many possible combined strategies which complicate personalizing treatment. Here, we review the role of the PI3K/AKT/mTOR pathway in ER+ advanced breast cancer, highlighting the genomic contexts in which the various inhibitors of this pathway may have superior activity. We also discuss selected trials with agents targeting the PI3K/AKT/mTOR and related pathways as well as the rationale supporting the clinical development of triple combination therapy targeting ER, CDK4/6 and PI3K/AKT/mTOR in ER+ advanced breast cancer.

Effects of used and under-used doses of Transfluthrin-based insecticide on Caenorhabditis elegans metabolism.

Different classes of insecticide compounds have been employed to control insects and mosquitoes; Pyrethroids are one of the most common used in both urban and rural household environments. This study investigated the effects of exposure of two doses of commercial transfluthrin-based insecticide (T-BI) on behavior (body bends, pharyngeal pumping rate, and feeding attributes) and biochemical biomarkers (AChE, PolyQ40 aggregations, HSP, antioxidative SOD, CTL, and GST) following three different protocols (transgenerational, neonatal, and lifespan) in Caenorhabditis elegans model system. The relative calculated dose (RCD) and relative calculated half dose (RCHD) of T-BI were compared with those of the control (water). T-BI reduced the health span of worms treated during their whole life and changed biochemical and behavioral patterns due to progenitors' uterine (transgenerational) and neonatal exposures. It was inferred that the effects of T-BI are transgenerational and persistent and can be harmful to non-target species, including humans. In addition, our findings highlight that T-BI contact by progenitors accelerates the establishment of Huntington's disease and causes a cholinergic outbreak in offspring adulthood.

Comunicação de más notícias em unidade de terapia intensiva neonatal / Breaking bad news in neonatal intensive care units / Comunicación de malas noticias en la unidad de cuidados intensivos neonatales

Resumo O protocolo Spikes é um dos instrumentos mais didáticos para o ensino da habilidade de comunicar más notícias, que exige sensibilidade e preparo. Neste artigo foram analisadas as percepções de residentes de pediatria, bem como de mães de neonatos, sobre a comunicação de más notícias em uma unidade de terapia intensiva neonatal. Trata-se de estudo qualitativo, descritivo e exploratório, baseado na antropologia visual, no qual o protocolo Spikes foi empregado em dois grupos focais, com abordagem analítica de conteúdo de Bardin por categorias. Foram relatados problemas como ambiente inadequado para comunicar más notícias, limitações na percepção das mães, falta de disponibilidade médica para conversar, linguagem inadequada e dificuldade para lidar com emoções, esclarecer dúvidas e discutir estratégias com os familiares. A reflexões sobre essas questões visa melhorar o aprendizado teórico e estimular a autocrítica, buscando a empatia e a humanização da assistência.

Abstract The SPIKES protocol is one of the most didactic tools to teach the communication of bad news, a skill that requires sensitivity and preparation. This article analyzed the perceptions of pediatrics residents and the mothers of neonates about the communication of bad news in a neonatal intensive care unit. This is a qualitative, descriptive and exploratory study, based on visual anthropology, in which the SPIKES protocol was used in two focus groups, with Bardin's content analytics approach by categories. Problems were reported as inadequate environment to break bad news, limitations in the perception of mothers, lack of medical availability to talk, inadequate language and difficulty to deal with emotions, clarify doubts and discuss strategies with family members. Reflection on these issues aims to improve theoretical learning and stimulate self-criticism, seeking empathy and the humanization of care.

Resumen El protocolo SPIKES es uno de los instrumentos más didácticos para enseñar la capacidad de comunicar malas noticias, lo que requiere sensibilidad y preparación. Este estudio analizó las percepciones de los residentes de pediatría y de las madres de recién nacidos sobre la comunicación de malas noticias en una unidad de cuidados intensivos neonatales. Se trata de un estudio cualitativo, descriptivo y exploratorio, basado en la antropología visual, en que se utilizó el protocolo SPIKES en dos grupos focales para categorizar el enfoque analítico del contenido. Se reportaron problemas como ambiente inadecuado para comunicar malas noticias, limitaciones en la percepción de las madres, falta de disponibilidad médica para hablar, lenguaje inadecuado y dificultad para lidiar con las emociones, aclarar dudas y discutir estrategias con los miembros de la familia. Las reflexiones sobre estos temas pretenden mejorar el aprendizaje teórico y estimular la autocrítica, buscando una atención más empática y humanizada.

Household prallethrin-based insecticide toxicity on different C. elegans life stage: A possible sign of Huntington Disease.

Household insecticide is largely used for insect and ectoparasite control, in city centers as well as in the countryside. The pyrethroids are the most used class of insecticide, these compounds in low doses have low toxicity for mammalians, in comparison to other compounds, with insecticide effects. The contact of these compounds in sublethal doses begins in early life and many cases, in intrauterine life. Considerable diseases still with undefined etiology, such as neurodegenerative conditions, and Huntington's Disease (HD) is one of them. HD is related to overexpression of Polyglutamine (PolyQ40), its aggregation, and non-solubilization, which leads to neural, behavioral, and cognitive damage. In our study, we evaluate the effect of two sublethal doses of a prallethrin-based insecticide (P-BI), in three different Caenorhabditis elegans life stages transgenerational, neonatal, and lifespan. We evaluated the Body bends and pharyngeal pumping rate, and social feeding as behavioral biomarkers. As well as acetylcholinesterase activity (AChE), PolyQ40 aggregation, antioxidant enzymes, and heat shock protein (HSP) expression. We observe that the toxic effect of P-BI is more pronounced on transgenerational and lifespan exposure. Both sublethal doses of P-BI decreased the AChE activity and retard the HSP expression as well as increased the PolyQ40 aggregates indicating a clear biomarker for possible effect in the progression of the HD, by the environmental contamination.

Neuroprotective potential of Cannabis sativa-based oils in Caenorhabditis elegans.

Substances from the Cannabis sativa species, especially cannabidiol (CBD) and Delta-9-tetrahydrocannabinol (Δ9-THC), have attracted medical attention in recent years. The actions of these two main cannabinoids modulate the cholinergic nervous system (CholNS) involving development, synaptic plasticity, and response to endogenous and environmental damage, as a characteristic of many neurodegenerative diseases. The dynamics of these diseases are mediated by specific neurotransmitters, such as the GABAergic nervous system (GNS) and the CholNS. The nematode Caenorhabditis elegans is an important experimental model, which has different neurotransmitter systems that coordinate its behavior and has a transgene strain that encodes the human ß-amyloid 1-42 peptide in body wall muscle, one of the main proteins involved in Alzheimer´s disease. Therefore, the objective of this study was to evaluate the protective potential of terpenoids found in C. sativa in the GNS and CholNS of C. elegans. The effect of two C. sativa oils with variations in CBD and THC concentrations on acetylcholinesterase (AChE) activity, lipid peroxidation, and behavior of C. elegans was evaluated. C. sativa oils were efficient in increasing pharyngeal pumping rate and reducing defecation cycle, AChE activity, and ROS levels in N2 strains. In the muscle:Abeta1-42 strain, mainly when using CBD oil, worm movement, body bends, and pharyngeal pumping were increased, with a reduced AChE activity. Consequently, greater investments in scientific research are needed, in addition to breaking the taboo on the use of the C. sativa plant as an alternative for medicinal use, especially in neurodegenerative diseases, which have already shown positive initial results.

Dietary transference of 17α-ethinylestradiol changes the biochemical and behavioral biomarkers in adult zebrafish (Danio rerio).

The endocrine disruptors (ED), even in low concentration, can change the homeostasis of an organism through the biochemical and physiological pathways; and are gaining more relevance due to their well-reported presence in the natural environment. EDs mainly affect non-target animals, which can bioaccumulate, leading to changes in metabolism. Another problem is due to several organisms that compose the aquatic biota serving as a basis of the food chain and transferring it to higher trophic levels. Here we evaluated the dietary transference of 17α-ethinylestradiol (EE2), in adult zebrafish chronically fed by EE2-bioaccumulated brine shrimp (BS). For this, we evaluated behavioral biomarkers such as the novel tank test (NTT), social preference test (SPT), mirror-induced aggressivity (MIA), and biochemical biomarkers such as acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CTL), and glutathione-S-transferase (GST) activity, cortisol, and lipid peroxidation levels in adult zebrafish. The behavioral effects can be explained by the changed effects on acetylcholinesterase activity as well as in the antioxidant system mainly affected by the high levels of EE2 identified by HPLC shown that had occurred during a dietary transfer for fish. EE2 has a potential pattern for bioaccumulation and dietary transfer in biological tissue and EE2 can affect the behavior of fish. The observed effects could be dangerous to the environment, affecting, other animals and even human health.

Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.

Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.

Aurora Kinase A and Bcl-xL Inhibition Suppresses Metastasis in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 10-15% of all breast cancer cases. Within TNBC, the treatment of basal B is the most challenging due to its highly invasive potential, and thus treatments to suppress metastasis formation in this subgroup are urgently needed. However, the mechanisms underlying the metastatic ability of TNBC remain unclear. In the present study, we investigated the role of Aurora A and Bcl-xL in regulating basal B cell invasion. We found gene amplification and elevated protein expression in the basal B cells, which also showed increased invasiveness in vitro, compared to basal A cells. Chemical inhibition of Aurora A with alisertib and siRNA-mediated knockdown of BCL2L1 decreased the number of invading cells compared to non-treated cells in basal B cell lines. The analysis of the correlation between AURKA and BCL2L1 expression in TNBC and patient survival revealed significantly decreased relapse-free survival (n = 534, p = 0.012) and distant metastasis-free survival (n = 424, p = 0.017) in patients with primary tumors exhibiting a high combined expression of AURKA and BCL2L1. Together, our findings suggest that high levels of Aurora A and Bcl-xL promote metastasis, and inhibition of these proteins may suppress metastasis and improve patient survival in basal B TNBC.

Persistent and transgenerational effects of pesticide residues in zebrafish.

Highly toxic chemical compounds are present in rivers and lakes, endangering the survival of non-target species. To evaluate the effects of environmental contamination on non-target species, we used the zebrafish as an animal model. Environmental concentrations of the widely used pesticides, glyphosate (GBH) at 4.8 µg·L-1 and 2,4-dichlorophenoxyacetic acid (DBH) at 3.4 µg·L-1, were used. The animals were exposed during the entire period of organogenesis and evaluated in our previous study regarding initial developmental parameters. In the present study, we evaluate these fish when achieve the adult phase, using the novel tank test (NTT) and the aversivity test. In the second step, the animals were allowed to reproduce, and the initial parameters of development, behavioral parameters in the open field test (OFT) and in the aversivity test (AST), and biochemical biomarkers as acetylcholinesterase (AChE), catalase (CAT), and superoxide dismutase (SOD) in the F1 generation were studied. Fish exposed to GBH showed hypermobility, and their anti-predatory reaction was impaired during adulthood, indicating a persistent effect. We also showed that fish had impaired behavioral and survival changes in the F1 generation as well as effects on AChE activity and antioxidant enzymes, characterizing a transgenerational effect. The fish did not show persistent effects in adulthood due to DBH exposure; however, they were unable to reproduce. Our findings demonstrate the serious impact of pesticides on fish, where the effects of contamination can affect future generations and compromise the species' survival.