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Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for renal replacement therapy, all of which impede optimal patient care. Various proactive measures, such as aggressive hydration and diuresis, have been identified as potential strategies to mitigate AKI; however, preventing its occurrence during chemotherapy remains challenging. Additionally, several factors, including intravascular volume depletion, sepsis, exposure to other nephrotoxic agents, tumor lysis syndrome, and direct damage from cancer's pathophysiology, frequently contribute to or exacerbate kidney injury. This article aims to comprehensively review the epidemiology, mechanisms of injury, diagnosis, treatment options, and prevention strategies for AKI induced by conventional chemotherapy.
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Temperature and humidity are studied in the context of seasonal infections in temperate and tropical zones, but the relationship between viral trends and climate variables in temperate subtropical zones remains underexplored. Our retrospective study analyzes respiratory pathogen incidence and its correlation with climate data in a subtropical zone. Retrospective observational study at Moinhos de Vento Hospital, South Brazil, aiming to assess seasonal trends in respiratory pathogens, correlating them with climate data. The study included patients of all ages from various healthcare settings, with data collected between April 2022 and July 2023. Biological samples were analyzed for 24 pathogens using polymerase chain reaction and hybridization techniques; demographic variables were also collected. The data was analyzed descriptively and graphically. Spearman tests and Poisson regression were used as correlation tests. Tests were clustered according to all pathogens, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, rhinovirus, and respiratory syncytial virus (RSV). Between April 2022 and July 2023, 3329 tests showed a 71.6% positivity rate. Rhinovirus and RSV predominated, exhibiting seasonal patterns. Temperature was inversely correlated with the viruses, notably rhinovirus, but SARS-CoV-2 was positively correlated. Air humidity was positively correlated with all pathogens, RSV, rhinovirus, and atmospheric pressure with all pathogens and rhinovirus. Our results showed statistically significant correlations, with modest effect sizes. Our study did not evaluate causation effects. Despite the correlation between climate and respiratory pathogens, our work suggests additional factors influencing transmission dynamics. Our findings underscore the complex interplay between climate and respiratory infections in subtropical climates.
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COVID-19 , Humedad , Estaciones del Año , Temperatura , Humanos , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Brasil/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Niño , Adolescente , Preescolar , Anciano , Adulto Joven , Lactante , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Clima , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Clima Tropical , Recién Nacido , Rhinovirus/genética , Rhinovirus/aislamiento & purificación , Incidencia , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Anciano de 80 o más AñosRESUMEN
Myrcene (ß-myrcene), found in essential oils from plant species such as hops and cannabis, has many advantageous properties, but its use is limited due to volatility and low solubility in water. One way to circumvent these limitations is to encapsulate the essential oils in a polymer matrix. However, these hydrophobic molecules are difficult to quantify when dispersed in water. Seeking to study the release of this terpene in drug release tests from polymeric matrices, this work aimed to develop an easy and cheap UV spectrophotometric method for the quantification of ß-myrcene in aqueous medium. To achieves this goal, samples were prepared in 0.05% (w/v) polysorbate 80 solution, with concentrations of ß-myrcene ranging from 0.01% to 0.1% (v/v), and were analyzed at 226 nm. Each sample was analyzed in triplicate and repeated on three different days, to evaluate the repeatability of the results. The results were subjected to Q, F and Student's t-tests. The regression parameters obtained for ß-myrcene were above 0.99 and through statistical analysis, it was possible to confirm the repeatability for the results. The values of the limits of detection and quantification indicated that the method is not affected by intrinsic factors of the equipment. The results of accuracy, robustness and selectivity showed recovery rates within acceptable limits. This demonstrates that the quantification of ß-myrcene in aqueous medium by UV spectrophotometry is feasible.
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Quitosano , Espectrofotometría Ultravioleta , Agua , Espectrofotometría Ultravioleta/métodos , Agua/química , Quitosano/química , Monoterpenos Acíclicos/análisis , Monoterpenos Acíclicos/química , Alquenos/análisis , Alquenos/química , Polisorbatos/química , Polisorbatos/análisis , Solubilidad , Reproducibilidad de los Resultados , Aceites Volátiles/análisis , Aceites Volátiles/químicaRESUMEN
BACKGROUND: Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension. OBJECTIVE: To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors. METHODS: Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 µM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 µmol/kg of the selected compound LASSBio-2062. RESULTS: Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 µM, respectively. LASSBio-2062 (30 µmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062. CONCLUSIONS: The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension.
FUNDAMENTO: A hipertensão arterial sistêmica é um fator de risco para disfunções cardíacas, renais e metabólicas. A busca por novas estratégias para prevenir e tratar doenças cardiovasculares levou à síntese de novas N-acilidrazonas para produzir efeito anti-hipertensivo. Os receptores de adenosina são um alvo alternativo para reduzir a pressão arterial devido à sua ação vasodilatadora e propriedades antioxidantes, que podem reduzir o estresse oxidativo característico da hipertensão arterial sistêmica. OBJETIVO: Avaliar o perfil anti-hipertensivo de novos compostos contendo selênio desenvolvidos para melhorar sua interação com os receptores de adenosina. MÉTODOS: Foi avaliada a reatividade vascular, registrando-se a tensão isométrica da aorta torácica pré-contraída de ratos Wistar machos após exposição a concentrações crescentes de cada derivado (0,1 a 100 µM). Para investigar o efeito anti-hipertensivo em ratos espontaneamente hipertensos, foram determinadas a pressão arterial sistólica, pressão arterial diastólica, pressão arterial média e a frequência cardíaca após administração intravenosa de 10 e 30 µmol/kg do composto selecionado LASSBio-2062. RESULTADOS: Os compostos denominados LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092 e LASSBio-2093 promoveram vasodilatação com concentrações efetivas médias de 15,5 ± 6,5; 14,6 ± 2,9; 18,7 ± 9,6; 6,7 ± 4,1; > 100; 6,0 ± 3,6; 37,8 ± 11,8; e 15,9 ± 5,7 µM, respectivamente. O LASSBio-2062 (30 µmol/kg) reduziu a pressão arterial média em ratos espontaneamente hipertensos de 124,6 ± 8,6 para 72,0 ± 12,3 mmHg (p < 0,05). A ativação do receptor de adenosina subtipo A3 e dos canais de potássio parece estar envolvida no efeito anti-hipertensivo do LASSBio-2062. CONCLUSÕES: O novo agonista do receptor de adenosina e ativador dos canais de potássio é um potencial agente terapêutico para o tratamento da hipertensão arterial sistêmica.
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Antihipertensivos , Hipertensión , Ratas , Animales , Masculino , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Ratas Endogámicas SHR , Ratas Wistar , Hipertensión/tratamiento farmacológico , Presión Sanguínea , Canales de PotasioRESUMEN
Pseudomonas aeruginosa is commonly associated with the ability to acquire antimicrobial resistance. The surveillance of resistance genes in various environmental matrices has gained prominence in recent years, being seen as a potential threat to public health. The objective of this study was to investigate genes encoding metallo-beta-lactamases (MBLs), which confer resistance to carbapenems, in wastewater. Fifteen isolates of P. aeruginosa were collected for five months from samples obtained from a municipal wastewater treatment plant in Rio Grande do Sul. These isolates were subjected to disk diffusion testing using 10 different antimicrobials. Phenotypic enzymatic tests for MBLs were conducted, and positive isolates underwent DNA extraction and gene detection using the polymerase chain reaction. The resistance rate to ceftazidime was 100%, cefepime 73.3%, piperacillin-tazobactam 66.67%, imipenem 53.30%, levofloxacin 46.67%, tobramycin 40%, and ciprofloxacin and amikacin 13.33%. Both meropenem and aztreonam resistances were rare accounting for 6.60% of the tested isolates. Among these isolates, 20% were classified as multidrug-resistant and were found to carry the blaNDM and blaSPM genes. The results suggest that evaluating resistance genes in bacteria from urban raw sewage can provide data that assist in surveillance, as this environment can stimulate increased bacterial resistance.
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Antibacterianos , Pseudomonas aeruginosa , Aguas Residuales , beta-Lactamasas , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Aguas Residuales/microbiología , Brasil , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
PURPOSE: Since the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates. METHODS: This study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection. RESULTS: Sampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine. CONCLUSIONS: This study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population's clinical manifestations and prevent future outbreaks of respiratory viruses.
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COVID-19 , Coinfección , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Virus , Niño , Adulto , Humanos , Anciano , COVID-19/epidemiología , Coinfección/epidemiología , Pandemias , Estudios Retrospectivos , Brasil/epidemiología , Vacunas contra la COVID-19 , Infecciones del Sistema Respiratorio/diagnóstico , SARS-CoV-2RESUMEN
Since starts the coronavirus disease 2019 (COVID-19) pandemic identified the presence of genomic fragments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various environmental matrices: domestic sewage, surface waters, and contaminated freshwater. Environmental monitoring of SARS-CoV-2 is a tool for evaluating trend curves over the months, compared to several clinical cases of the disease. The objective of this study was to monitor the SARS-CoV-2 in environmental samples collected in different sites in a metropolitan area of Porto Alegre, Southern Brazil. During 10 months from 2020 to 2021, 300 samples were collected weekly and biweekly from nine points located in 3 cities: one point from a wastewater treatment plant (WWTP) in São Leopoldo (fortnightly collection), two points in Dilúvio Stream in Porto Alegre (fortnightly collection), two points in Pampa and Luiz Rau Streams (weekly collection), and two points in public fountains (fortnightly collection) in Novo Hamburgo. After collection, samples were concentrated by ultracentrifugation, and viral nucleic acids were extracted using MagMax® Core Nucleic Acid Purifications kits and submitted to RT-qPCR, using E, N1, and N2 gene targets of SARS-CoV-2. Only 7% (3/41) samples from public fountains were positive, with a mean viral load (VL) of SARS-CoV-2 RNA of 5.02 × 101 gc/l (2.41~8.59 × 101 gc/l), while the streams had average VL of 7.43 × 105 gc/l (Pampa), 7.06 × 105 gc/l (Luiz Rau), 2.01 × 105 gc/l (Dilúvio), and 4.46 × 105 cg/l (WWTP). The results showed varying levels of viral presence in different sample types, with a demonstrated correlation between environmental viral load and clinical COVID-19 cases. These findings contribute to understanding virus persistence and transmission pathways in the environment. Continuous monitoring, especially in less developed regions, is crucial for early detection of vaccine resistance, new variants, and potential COVID-19 resurgence.
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COVID-19 , SARS-CoV-2 , Humanos , ARN Viral , Brasil/epidemiología , Monitoreo del AmbienteRESUMEN
Resumo Fundamento A hipertensão arterial sistêmica é um fator de risco para disfunções cardíacas, renais e metabólicas. A busca por novas estratégias para prevenir e tratar doenças cardiovasculares levou à síntese de novas N-acilidrazonas para produzir efeito anti-hipertensivo. Os receptores de adenosina são um alvo alternativo para reduzir a pressão arterial devido à sua ação vasodilatadora e propriedades antioxidantes, que podem reduzir o estresse oxidativo característico da hipertensão arterial sistêmica. Objetivo Avaliar o perfil anti-hipertensivo de novos compostos contendo selênio desenvolvidos para melhorar sua interação com os receptores de adenosina. Métodos Foi avaliada a reatividade vascular, registrando-se a tensão isométrica da aorta torácica pré-contraída de ratos Wistar machos após exposição a concentrações crescentes de cada derivado (0,1 a 100 μM). Para investigar o efeito anti-hipertensivo em ratos espontaneamente hipertensos, foram determinadas a pressão arterial sistólica, pressão arterial diastólica, pressão arterial média e a frequência cardíaca após administração intravenosa de 10 e 30 μmol/kg do composto selecionado LASSBio-2062. Resultados Os compostos denominados LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092 e LASSBio-2093 promoveram vasodilatação com concentrações efetivas médias de 15,5 ± 6,5; 14,6 ± 2,9; 18,7 ± 9,6; 6,7 ± 4,1; > 100; 6,0 ± 3,6; 37,8 ± 11,8; e 15,9 ± 5,7 μM, respectivamente. O LASSBio-2062 (30 μmol/kg) reduziu a pressão arterial média em ratos espontaneamente hipertensos de 124,6 ± 8,6 para 72,0 ± 12,3 mmHg (p < 0,05). A ativação do receptor de adenosina subtipo A3 e dos canais de potássio parece estar envolvida no efeito anti-hipertensivo do LASSBio-2062. Conclusões O novo agonista do receptor de adenosina e ativador dos canais de potássio é um potencial agente terapêutico para o tratamento da hipertensão arterial sistêmica.
Abstract Background Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension. Objective To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors. Methods Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 μM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 μmol/kg of the selected compound LASSBio-2062. Results Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 μM, respectively. LASSBio-2062 (30 μmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062. Conclusions The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension.
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Background: The 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is the most used equation to estimate glomerular filtration rate (GFR), with race being a factor thereof, increasing GFR by 16% in self-identified Black persons compared with non-Black persons. However, recent publications indicate that it might overestimate GFR for Black adults outside the USA. In this meta-analysis, we assessed the accuracy, evaluated by the percentage of estimated GFR within 30% of measured GFR (P30), of the 2009 CKD-EPI equation in estimating GFR with and without the race coefficient in Black individuals outside the United States of America (USA). Methods: We searched MEDLINE and Embase from inception to 9 July 2022, with no language restriction, supplemented by manual reference searches. Studies that assessed the CKD-EPI P30 accuracy with or without the race coefficient in Black adults outside the USA with an adequate method of GFR measurement were included. Data were extracted by independent pairs of reviewers and were pooled using a random-effects model. Results: We included 11 studies, with a total of 1834 Black adults from South America, Africa and Europe. The race coefficient in the 2009 CKD-EPI equation significantly decreased P30 accuracy {61.9% [95% confidence interval (CI) 53-70%] versus 72.9% [95% CI 66.7-78.3%]; P = .03}. Conclusions: Outside the USA, the 2009 CKD-EPI equation should not be used with the race coefficient, even though the 2009 CKD-EPI equation is not sufficiently accurate either way (<75%). Thus we endorse the Kidney Disease: Improving Global Outcomes guidelines to use exogenous filtration markers when this may impact clinical conduct.
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OBJECTIVE: Evaluate vocal quality in patients with OSA before and after continuous use of CPAP with a humidifier using subjective patient perception and clinical assessment. The hypothesis was that CPAP treatment with a humidifier would benefit voice quality. STUDY DESIGN: Randomized, sham-controlled, blinded clinical trial. METHODS: Forty-three natal males with obstructive sleep apnea for whom CPAP treatment was recommended following polysomnography were randomized into two therapy groups: CPAP and Sham-CPAP. Participants completed questionnaires on voice use, a voice self-assessment with the ten-item vocal handicap index (VHI-10), and complementary questionnaires: the Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), reflux symptoms index (LPRSI) and oral dryness visual analog scale (DRY). Their voices were recorded at three different times: before CPAP therapy, and after 3 and 6 months of continuous CPAP use. The acoustic voice quality index (AVQI), and an auditory-perceptual judgment (APJ) were also applied before and after the CPAP and Sham treatments. RESULTS: After 6 months of treatment, the CPAP group presented improvements in their sleep patterns; however, no statistically significant differences were observed between the groups in respect of the results of the voice-related questionnaires, the AVQI values, and the APJ of the voice quality. All of the participants had some degree of vocal deviation at baseline. CONCLUSIONS: CPAP therapy with a humidifier did not improve vocal quality as evaluated by the clinician or patient self-assessment. However, it did not have any significant negative effects on voice quality, so can be considered safe to use in male OSA patients.
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Fertile soil known as Amazonian dark earth is central to the debate over the size and ecological impact of ancient human populations in the Amazon. Dark earth is typically associated with human occupation, but it is uncertain whether it was created intentionally. Dark earth may also be a substantial carbon sink, but its spatial extent and carbon inventory are unknown. We demonstrate spatial and compositional similarities between ancient and modern dark earth and document modern Indigenous practices that enrich soil, which we use to propose a model for the formation of ancient dark earth. This comparison suggests that ancient Amazonians managed soil to improve fertility and increase crop productivity. These practices also sequestered and stored carbon in the soil for centuries, and we show that some ancient sites contain as much carbon as the above-ground rainforest biomass. Our results demonstrate the intentional creation of dark earth and highlight the value of Indigenous knowledge for sustainable rainforest management.
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Carbono , Suelo , Humanos , Biomasa , Secuestro de Carbono , Producción de CultivosRESUMEN
No Brasil, a assistência em tempo oportuno aos indivíduos convivendo com Doença de Chagas ainda é um desafio à saúde pública. Objetivou-se analisar o itinerário terapêutico de crianças e adolescentes portadores de Doença de Chagas na busca de atenção e cuidado com a saúde. Adotada a abordagem qualitativa, descritiva, exploratória. Pesquisa de campo realizada com familiares de crianças/adolescentes convivendo com Doença de Chagas no Centro de Referência em Doenças Tropicais (CRDT) em Macapá, AP. Análise de conteúdo subsidiou a identificação de três categorias analíticas: o diagnóstico como desafio inicial do itinerário terapêutico; o Itinerário em busca do tratamento e controle da doença; fragilidades e potencialidades dos serviços de atenção à saúde. Os resultados apontaram que a oferta dos serviços voltados para o diagnóstico da doença ainda está centrada na atenção especializada. Portanto, o itinerário terapêutico de crianças e adolescentes portadores de Doença de Chagas em busca do tratamento e controle da doença é marcado por desafios que envolvem o diagnóstico em tempo oportuno, o que pode repercutir em tratamentos equivocados. A principal fragilidade identificada estava relacionada aos serviços de saúde, pois a atenção primária não está preparada para a identificação da doença, tão pouco a média e alta complexidade estão qualificadas para uma assistência resolutiva. Quanto às potencialidades, estão relacionadas ao sistema de cuidado e atenção à saúde.
In Brazil, time assistance for individuals living with Chagas disease is still a challenge to public health. It was aimed at analyzing the therapeutic itinerary of children and adolescents with Chagas disease in search of health care and care. Adopted the qualitative, descriptive, exploratory approach. Field research conducted with family members of children/adolescents living with Chagas disease at the Reference Center for Tropical Diseases in Macapá, AP. Content analysis subsidized the identification of three analytical categories: diagnosis as an initial challenge of the therapeutic itinerary; the itinerary in search of disease treatment and control; weaknesses and potentialities of health care services. The results pointed out that the offer of services focused on the diagnosis of the disease is still centered on specialized care. Therefore, the therapeutic itinerary of children and adolescents with Chagas disease in search of treatment and control of the disease is marked by challenges involving the diagnosis in a timely manner, which can reverberate in wrong treatments. The main fragility identified was related to health services, as primary care is not prepared for the identification of the disease, nor are the medium and high complexity qualified for resolution care. Potentialities are related to the health care system and care.
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Salud Pública , Enfermedad de ChagasRESUMEN
INTRODUCTION: Oral administration of poorly water-soluble drugs (PWSDs) is generally related to low bioavailability, leading to high drug doses, multiple side effects, and low patient compliance. Thus, different strategies have been developed to increase drug solubility and dissolution in the gastrointestinal tract, opening new venues for these drugs. AREAS COVERED: This review outlines the current challenges in PWSD formulation development and the strategies to overcome the oral barriers and increase their solubility and bioavailability. Conventional strategies include altering crystalline and molecular structures and modifying oral solid dosage forms. In contrast, novel strategies comprise micro- and nanostructured systems. Recent representative studies involving how these strategies have improved the oral bioavailability of PWSDs were also reviewed and reported. EXPERT OPINION: New approaches to enhance PWSD bioavailability have sought to improve water solubility and dissolution rates, drug protection by overcoming biological barriers, and increased absorption. Still, only a handful of studies have focused on quantifying the increase in bioavailability. Improving the oral bioavailability of PWSDs remains an exciting unexplored field of research and has become an important issue for successfully developing pharmaceutical products.
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Sistemas de Liberación de Medicamentos , Agua , Humanos , Preparaciones Farmacéuticas/química , Disponibilidad Biológica , Agua/química , Administración Oral , SolubilidadRESUMEN
Embora as fraturas por fragilidade sejam importantes detratoras de qualidade de vida relacionada à saúde, aumentando a morbimortalidade e acarretando alto impacto clínico, psicossocial e econômico, elas são pouco valorizadas e negligenciadas por médicos e até mesmo por pacientes. Além disso, os critérios de priorização para avaliação de novas tecnologias, em geral, não consideram critérios além dos financeiros para uma tomada de decisão mais inclusiva e assertiva para o tratamento da população de mais alto risco de fratura. Assim, este artigo visa revisitar alguns diferentes pontos de vista e trazer uma reflexão sobre critérios e prioridades na osteoporose. Para isso, foi considerada a perspectiva de múltiplos atores no processo de tomada de decisão em saúde, bem como analisadas as falhas na atenção a uma doença de alta prevalência e que, além do grande impacto econômico gerado para a sociedade, causa repercussões emocionais, incapacidade gerada por fraturas e medo de novas quedas ou pequenos traumas.
Although fragility fractures are important detractors of health-related quality of life, increasing morbidity and mortality and causing a high clinical, psychosocial, and economic impact, they are undervalued and neglected by physicians and even patients. In addition, prioritization criteria for evaluating new technologies, in general, do not consider criteria other than financial ones for a more inclusive and assertive decision-making for the treatment of the population at higher risk of fracture. Thus, this article aims to revisit some different points of view and bring a reflection on criteria and priorities in osteoporosis. For this, the perspective of multiple stakeholders in the health decision-making process was considered, as well as the failures in the care of this highly prevalent disease that, in addition to the great economic impact generated for society, causes emotional repercussions, disability generated by fractures and fear of further falls or minor trauma.
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Osteoporosis , Teoría de las Decisiones , Fracturas OsteoporóticasRESUMEN
With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. These processes could result in genetic introgression and the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of the Spike gene. The 5' genome portion (circa 22 kb) resembles the AY.101 (Delta), and the 3' genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 (Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, AYBA-RS, is one of the dozens of recombinants described in 2022. The submission of only four sequences in the GISAID database suggests that this lineage had a minor epidemiological impact. However, the recent emergence of this and other Deltacron recombinant lineages (XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that supports this assertion, concluding that this stresses the need for continued genomic surveillance. This monitoring is vital for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.
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BACKGROUND: Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of the cuticle. Treatment involves clinical measures and, when there is no response or the hypertrophy of the folds is very pronounced, surgical treatment is indicated. Post-surgical histopathology is little studied in the literature. In this sense, we believe that the histopathological study is important not only for the individualized understanding of the patient's chronic disease, avoiding relapses, but also for the understanding of its pathophysiology and treatment possibilities. OBJECTIVE: To describe the histopathological changes found in biopsies of the proximal nail fold of patients with chronic paronychia undergoing surgical treatment. MATERIALS AND METHODS: A histopathological study of 16 nail folds from 6 patients after surgery was performed at 2 study centers. RESULTS: The most prevalent epidermal findings were orthokeratosis, hypergranulosis, acanthosis and spongiosis and the dermal findings were fibrosis and mononuclear inflammatory infiltrate. CONCLUSION: The histopathological study allowed us to conclude that chronic paronychia is primarily an inflammatory process, but it is not possible to conclude whether microorganisms such as Candida and bacterial cocci are part of the etiology or just secondary and opportunistic agents.
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Queratosis , Neoplasias , Paroniquia , Humanos , Paroniquia/tratamiento farmacológico , Uñas/patología , Neoplasias/complicaciones , Fibrosis , Enfermedad Crónica , Queratosis/patología , Hipertrofia/complicaciones , Hipertrofia/patologíaRESUMEN
CONTEXT: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. OBJECTIVES: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. METHODS: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan-Meier and Cox regression methods. RESULTS: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI <20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597-11.992) and mGPS (HR 1.843-2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678-8.938) and mGPS (HR 2.103-2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0-1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI >28 kg/m2) to 44% (mGPS 2, BMI <20 kg/m2). CONCLUSION: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts.
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Neoplasias , Humanos , Estudios Prospectivos , Neoplasias/diagnóstico , Neoplasias/terapia , Pronóstico , Inflamación , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Resumo Objetivo Estimar a prevalência da síndrome de fragilidade e sua associação com variáveis socioeconômicas, demográficas e de saúde, em idosos atendidos em duas Unidades de Saúde (US) no município de Rio Branco, Acre, no período de outubro de 2016 a junho de 2017. Método A prevalência de síndrome de fragilidade foi medida pela Edmonton Frail Scale (EFS), investigada em uma amostra calculada de 298 pessoas idosas, selecionadas aleatoriamente por meio de sorteio. Utilizou-se a Regressão de Poisson, com variância robusta e intervalos de confiança de 95%, para estimar as razões de prevalência e definir o modelo ajustado. Todas as análises levaram em consideração os pesos. Resultados Verificou-se que 35,1% da amostra apresentou fragilidade. A prevalência de fragilidade foi associada a ter 75 anos ou mais, inatividade física, risco nutricional, deficit cognitivo, percepção negativa da saúde, usar 5 ou mais medicamentos e ter/histórico de câncer, queda no último ano, morar sozinho, segurança de bairro insatisfatória e ser da etnia/cor não branca. Conclusão Verificou-se o perfil de alerta para rastreio da fragilidade, que poderá auxiliar na prática clínica dos profissionais das US da população de estudo e, ainda, considera a necessidade de implantação e fortalecimento de programas de atenção à saúde da pessoa idosa e atuação de matriciamento e/ou grupos de apoio multiprofissional à Saúde da Família.
Abstract Objective To estimate the prevalence of frailty syndrome and its association with socioeconomic, demographic and health variables, in elderly people treated at two Health Units in the city of Rio Branco, Acre, from October 2016 to June 2017. Method The prevalence of frailty was measured using the Edmonton Frail Scale (EFS), and associations were tested with selected variables. Poisson regression, with robust variance and 95% confidence intervals, was used to estimate the prevalence ratios and define the adjusted model. All analyzes took into account the sample weights and were performed using SPSS version 20. Results It was found that 35.1% of the sample showed fragility. The prevalence of frailty was associated with being 75 years old or more, physical inactivity, nutritional risk, cognitive deficit, negative health perception, using 5 or more medications and having/history of cancer, falls in past year, living alone, unsatisfactory neighborhood safety and being of ethnicity/non-white color. Conclusion The alert profile for screening for frailty was verified, which may assist in the clinical practice of FHS professionals in the study population, and also considers the need to implement and strengthen eldely's health care programs and performance of the Family Health Support Centers.
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Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence of diabetes is increasing, a concomitant increase in CAN is expected and will reduce quality of life and increase mortality. Autonomic dysfunction is associated with reduced baroreflex sensitivity and impairment of sympathetic and parasympathetic modulation. Various autonomic function tests are used to diagnose CAN, a condition without adequate treatment. It is important to consider the control of glucose level and blood pressure as key factors for preventing CAN progression. However, altered biomarkers of inflammatory and endothelial function, increased purinergic receptor expression, and exacerbated oxidative stress lead to possible targets for the treatment of CAN. The present review describes the molecular alterations seen in CAN, diagnosis, and possible alternative treatments.
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Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-α, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.