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Introduction: Brazil is a developing and an Upper Middle Income, categorized by the World Bank. Therefore, it is a country that needs a special vision for children with oncological diseases who require Pediatric Palliative Care. This study aimed to understand the specificities of services that provide oncology services in comparison to those that do not provide oncological care. Methods: This is a descriptive, cross-sectional, and online survey study. A questionnaire was created by a multidisciplinary group of leaders from the Brazilian Pediatric Palliative Care Network and then the survey was distributed using a snowball strategy. Results: Of the 90 services that answered the questionnaire, 40 (44.4%) attended oncologic patients. The Southeast represented most of the services (57.57%), followed by the Northeast, with 18.89% (17 services), the South with 12.22% (11 services), and the Center West with 8.89% (8 services). No differences were observed in access to opioid prescriptions between the services. It was observed that those services that attended oncologic patients had a tendency to dedicate more time to Pediatric Palliative Care. Discussion: The distribution of services that cover oncology and those that do not, are similar in the different regions of Brazil. In Brazil, there are difficulties in accessing opioids in pediatrics: access to opioid prescriptions without differences revealed that even pediatric oncologists might have difficulty with this prescription, and this should improve. It is concluded that education in Pediatric Palliative Care is the key to improvements in the area.
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A polyethylene (PE) film surface modification method is proposed via benzoic acid (BA) alkylation grafting to improve the surface affinity to polar substances. The procedure involves sequentially spraying AlCl3 and BA onto the heat-softened PE surface. The occurrence of the alkylation reaction was evaluated through comparative chemical, morphological, and thermal analyses. It was demonstrated that the grafting reaction of BA onto the PE film surface took place, limited to the surface layer, while preserving the bulk properties of PE. The reaction resulted in the formation of aluminum benzoate complexes, which improved the surface affinity to polar compounds. The impact of grafting on the surface properties of PE was further assessed by comparing the behavior of PE films treated with BA and untreated PE films when painted with watercolors. The PE film grafted with BA exhibited increased affinity towards watercolors, providing strong evidence of a change in surface polarity from hydrophobic to hydrophilic. These findings indicate that the proposed methodology effectively renders the PE surface paintable, even with non-toxic water-based inks, making it suitable for applications such as packaging.
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The interface between pediatric palliative care (PPC) and inborn metabolic diseases (IMD) remains incipient, though these conditions fill the state of art of complex chronic diseases, eligible to this health approach. We analyzed the medical records of PPC clinic during the years 2001 to 2021 and the IMD outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC and IMD. Among outpatients, 14% were diagnosed with IMD, which were referred to the PPC service earlier compared to Non-IMD cases. The Group 3 (complex molecules) was the most frequent (64.7%), following by Group 1 representing by small molecules (21.6%), the latter having a lower median age at diagnosis when compared to the former (0.7 vs. 5.2 years, p = 0.001). The sphingolipidoses were the pathologies most frequent in our cohort, in line with what was observed in the literature. There were no differences between IMD groups in terms of diagnosis and PPC referral age, however in Non-IMD conditions, the age of diagnosis were earlier than IMD. Nevertheless, IMD group showed lower age of referral to PPC. The IMD comprises large fraction of outpatients in the PPC setting, thus further studies are needed in this field.
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Lanthanide-doped up-converting nanoparticles (UCNPs) have emerged as promising biomedical tools in recent years. Most research efforts were devoted to the synthesis of inorganic cores with the optimal physicochemical properties. However, the careful design of UCNPs with the adequate surface coating to optimize their biological performance still remains a significant challenge. Here, we propose the functionalization of UCNPs with four distinct types of surface coatings, which were compared in terms of the provided colloidal stability and resistance to degradation in different biological-relevant media, including commonly avoided analysis in acidic lysosomal-mimicking fluids. Moreover, the influence of the type of particle surface coating on cell cytotoxicity and endocytosis/exocytosis was also evaluated. The obtained results demonstrated that the functionalization of UCNPs with poly(isobutylene-alt-maleic anhydride) grafted with dodecylamine (PMA-g-dodecyl) constitutes an outstanding strategy for their subsequent biomedical application, whereas poly(ethylene glycol) (PEG) coating, although suitable for colloidal stability purposes, hinders extensive cell internalization. Conversely, surface coating with small ligand were found not to be suitable, leading to large degradation degrees of UCNPs. The analysis of particle' behavior in different biological media and in vitro conditions here performed pretends to help researchers to improve the design and implementation of UCNPs as theranostic nanotools.
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Endocitosis , Nanopartículas , Propiedades de Superficie , Endocitosis/efectos de los fármacos , Humanos , Nanopartículas/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Polietilenglicoles/químicaRESUMEN
Background: The pediatric palliative care (PPC) sets up an interdisciplinary approach of chronic complex diseases throughout birth to adolescence. It encompasses countless contrasts in development and diagnosis scopes, which make this area a challenge to nonpediatric practitioners. Objective: We sought to assess the most prevalent diseases in follow-up of the PPC team. Methods: We analyzed the medical records of PPC clinic during the years 2001 and 2021 and the diagnosis of outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC. Results: The most prevalent diseases were epidermolysis bullosa (36.9%), followed by neurological Inherited Errors of Metabolism (IEM) diseases (19.0%), IEM diseases (14.3%), dysmorphological and chromosomal disorders (8.5%), skeletal disorders mainly osteogenesis imperfecta (6.9%), and liver transplantation conditions (5.5%) (p < 0.001). The less frequent conditions were external causes, such as neonatal insults or traffic accidents (2.8%), cancer (1.7%), congenital cardiopathies (1.4%), congenital infectious diseases (1.1%), gastrointestinal and hepatic conditions (0.8%), and rheumatological conditions (0.3%). The patients were older at diagnosis (6.9 years) and at PPC referral (13.2 years) than patients with epidermolysis bullosa and skeletal disorders and dysmorphological and chromosomal disorders were younger on referral. Conclusion: There are a lot of complex chronic conditions which could benefit from palliative care in pediatric setting. However, epidemiological and symptomatological assessment of the health service is necessary to provide an appropriate care to the country's reality.
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Trastornos de los Cromosomas , Epidermólisis Ampollosa , Recién Nacido , Adolescente , Niño , Humanos , Cuidados Paliativos , Brasil/epidemiología , Hospitales , Enfermedad CrónicaRESUMEN
BACKGROUND: Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. OBJECTIVE: To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. METHODS: Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. RESULTS: 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). STUDY LIMITATIONS: Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). CONCLUSION: Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.
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Epidermólisis Ampollosa , Secuenciación del Exoma , Humanos , Masculino , Femenino , Brasil , Niño , Preescolar , Epidermólisis Ampollosa/genética , Epidermólisis Ampollosa/patología , Adolescente , Colágeno Tipo VII/genética , Biopsia , Adulto Joven , Adulto , Mutación , Lactante , Piel/patología , Persona de Mediana Edad , Queratina-5/genéticaRESUMEN
Head and neck squamous cell carcinoma (HNSCC) exhibits considerable variability in patient outcome. It has been reported that SOX2 plays a role in proliferation, tumor growth, drug resistance, and metastasis in a variety of cancer types. Additionally, SOX9 has been implicated in immune tolerance and treatment failures. SOX2 and SOX9 induce treatment failure by a molecular mechanism that has not yet been elucidated. This study explores the inverse association of SOX2/SOX9 and their distinct expression in tumors, influencing the tumor microenvironment and radiotherapy responses. Through public RNA sequencing data, human biopsy samples, and knockdown cellular models, we explored the effects of inverted SOX2 and SOX9 expression. We found that patients expressing SOX2LowSOX9High showed decreased survival compared to SOX2HighSOX9Low. A survival analysis of patients stratified by radiotherapy and human papillomavirus brings additional clinical relevance. We identified a gene set signature comprising newly discovered candidate genes resulting from inverted SOX2/SOX9 expression. Moreover, the TGF-ß pathway emerges as a significant predicted contributor to the overexpression of these candidate genes. In vitro findings reveal that silencing SOX2 enhances tumor radioresistance, while SOX9 silencing enhances radiosensitivity. These discoveries lay the groundwork for further studies on the therapeutic potential of transcription factors in optimizing HNSCC treatment.
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ABSTRACT Objective: To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes. Methods: Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied. Results: 33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30-36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2-304) and 25 days (13-58), respectively. Conclusions: Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.
RESUMO Objetivo: Descrever a população de recém-nascidos com síndrome de Patau (T13) e Edwards (T18) portadores de cardiopatias congênitas, que permaneceram em Unidades de Terapia Intensiva (UTI) de um complexo hospitalar quaternário, com relação a conduta cirúrgica ou não, cuidados paliativos e seus desfechos. Métodos: Série de casos de pacientes internados entre janeiro de 2014 a dezembro de 2018, com análise dos prontuários de portadores de T13 ou T18 que permaneceram internados em UTI que recebem neonatos nesse hospital quaternário. Utilizou-se análise estatística descritiva. Resultados: Foram identificados 33 prontuários para análise — 27 T18 (81,8%) e seis T13 (18,2%); 64% do sexo feminino e 36% do sexo masculino. Oito foram prematuros, nascidos com 30 a 36 semanas (24,2%), e apenas quatro nasceram com mais de 2500 g (12,1%). Quatro pacientes foram submetidos a cirurgia cardíaca e um deles foi a óbito. A mortalidade intra-hospitalar foi de 83% para T13 e 59% para T18. A maioria apresentava outras malformações e foi submetida a outras cirurgias. Cuidados paliativos foram oferecidos a 54% dos pacientes. A mediana do tempo de hospitalização para T18 e T13 foi respectivamente de 29 dias (variação: 2-304) e 25 dias (13-58). Conclusões: Pacientes com T13 e T18 cursam com alta morbimortalidade e longa permanência hospitalar em UTI. São necessários estudos multicêntricos para melhor análise de aspectos importantes para a criação de protocolos que, buscando proporcionalidade terapêutica, tragam melhor qualidade de vida para os pacientes e suas famílias.
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Abstract Background Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. Results 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). Study limitations Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). Conclusion Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.
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OBJECTIVE: To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes. METHODS: Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied. RESULTS: 33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30-36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2-304) and 25 days (13-58), respectively. CONCLUSIONS: Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.
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Trastornos de los Cromosomas , Lactante , Humanos , Masculino , Recién Nacido , Femenino , Síndrome de la Trisomía 18 , Trastornos de los Cromosomas/epidemiología , Síndrome de la Trisomía 13 , Cuidados Paliativos , Calidad de Vida , Recien Nacido Prematuro , Hospitales , Trisomía , Estudios RetrospectivosRESUMEN
Objetivo: Analisar a prática da episiotomia em uma maternidade de alto risco e seus fatores associados. Método: Trata-se de um estudo transversal que analisou um total de 333 fichas obstétricas anexadas aos prontuários de puérperas de uma maternidade de alto risco no período de janeiro a dezembro de 2021. Os dados foram coletados de agosto a dezembro do ano de 2022. A análise foi realizada de forma descritiva, utilizando-se o teste Qui-Quadrado a fim de comparar e delinear as proporções dos grupos de amostras de interesse. Resultados: Em 5,41% (18) das parturientes, realizou-se episiotomia; 66,67% (12) tinham histórico de síndrome hipertensiva na gestação; 55,56% (10) encontravam-se na faixa etária de 20-29 anos; das parturientes, 94,44% (17) pariram em posição litotômica; 94,44% (17) eram primíparas, sem acompanhante na hora do parto, 88,89% (16); e 66,11% (11) tiveram assistência prestada por profissional médico. Conclusão: Muitas são as barreiras a serem enfrentadas para promover e ressaltar o protagonismo da mulher durante o processo de parir, as informações trazidas por este estudo permitiram concluir a continuidade da prática da episiotomia. Com isso, espera-seque o estudo contribua para mudança, readequação e sensibilização das práticas obstétricas profissionais para que ocorra uma transformação desse cenário. Descritores: Episiotomia; Enfermagem Obstétrica; Parto Normal
Objective: To analyze the practice of episiotomy in a high-risk maternity hospital and its associated factorsMethods: This is a cross-sectional study, which analyzed a total of 333 obstetric records attached to the medical records of puerperal women in a high-risk maternity hospital from January to December 2021. Data were collected from August to December 2022. The analysis was performed descriptively, using the Chi-Square test in order to compare and delineate the proportions of the groups of samples interest. Results: In 5.41% (18) of the parturients, an episiotomy was performed, 66.67% (12) had a history of hypertensive syndrome during pregnancy, 55.56% (10) were in the age group of 20-29 years, of the parturients 94.44% (17) gave birth in a lithotomic position; 94.44% (17) were primiparous, unaccompanied at the time of delivery 88.89% (16) and had assistance provided by a medical professional 66.11% (11).Conclusion: There are many barriers to be faced to promote and emphasize the role of women during the process of delivery. The information brought by this study allowed us to conclude the continuity of episiotomy practice. Thus, it is expected that the study will contribute to change, readjustment and sensitization of professional obstetric practices, so that a transformation of this scenario occurs. Descriptors: Episiotomy; Obstetric Nursing. Normal delivery.
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Episiotomía , Parto Normal , Enfermería ObstétricaRESUMEN
Objetivo: Analisar a prática da episiotomia em uma maternidade de alto risco e seus fatores associados. Método: Trata-se de um estudo transversal que analisou um total de 333 fichas obstétricas anexadas aos prontuários de puérperas de uma maternidade de alto risco no período de janeiro a dezembro de 2021. Os dados foram coletados de agosto a dezembro do ano de 2022.A análise foi realizada de forma descritiva, utilizando-se o teste Qui-Quadrado a fim de comparar e delinear as proporções dos grupos de amostras de interesse. Resultados: Em 5,41% (18) das parturientes, realizou-se episiotomia; 66,67% (12) tinham histórico de síndrome hipertensiva na gestação; 55,56% (10) encontravam-se na faixa etária de 20-29 anos; das parturientes, 94,44% (17) pariram em posição litotômica; 94,44% (17) eram primíparas, sem acompanhante na hora do parto, 88,89% (16); e 66,11% (11) tiveram assistência prestada por profissional médico. Conclusão: Muitas são as barreiras a serem enfrentadas para promover e ressaltar o protagonismo da mulher durante o processo de parir, as informações trazidas por este estudo permitiram concluir a continuidade da prática da episiotomia. Com isso, espera-seque o estudo contribua para mudança, readequação e sensibilização das práticas obstétricas profissionais para que ocorra uma transformação desse cenário. Descritores: Episiotomia; Enfermagem Obstétrica; Parto Normal.
Objective: To analyze the practice of episiotomy in a high-risk maternity hospital and its associated factorsMethods: This is a cross-sectional study, which analyzed a total of 333 obstetric records attached to the medical records of puerperal women in a high-risk maternity hospital from January to December 2021. Data were collected from August to December 2022. The analysis was performed descriptively, using the Chi-Square test in order to compare and delineate the proportions of the groups of samples of interest.Results: In 5.41% (18) of the parturients, an episiotomy was performed, 66.67% (12) had a history of hypertensive syndrome during pregnancy, 55.56% (10) were in the age group of 20-29 years, of the parturients 94.44% (17) gave birth in a lithotomic position; 94.44% (17) were primiparous, unaccompanied at the time of delivery 88.89% (16) and had assistance provided by a medical professional 66.11% (11). Conclusion: There are many barriers to be faced to promote and emphasize the role of women during the process of delivery. The information brought by this study allowed us to conclude the continuity of episiotomy practice. Thus, it is expected that the study will contribute to change, readjustment and sensitization of professional obstetric practices, so that a transformation of this scenario occurs. Descriptors: Episiotomy; Obstetric Nursing; Normal delivery.
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Episiotomía , Parto Normal , Enfermería ObstétricaRESUMEN
Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.
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Neoplasias de la Mama , Nanocáscaras , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/metabolismo , Proteínas Proto-Oncogénicas c-akt , Oro , Receptor ErbB-2/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , ARN Interferente Pequeño , Línea Celular TumoralRESUMEN
Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανß3 y ανß5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.
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The application of high throughput synthesis methodologies in the generation of active pharmaceutical ingredients (APIs) currently requires the use of automated and easily scalable systems, easy dispensing of supported reagents in solution phase organic synthesis (SPOS), and elimination of purification and extraction steps. The recyclability and recoverability of supported reagents and/or catalysts in a rapid and individualized manner is a challenge in the pharmaceutical industry. This objective can be achieved through a suitable compartmentalization of these pulverulent reagents in suitable devices for it. This work deals with the use of customized polypropylene permeable-capsule devices manufactured by 3D printing, using the fused deposition modeling (FDM) technique, adaptable to any type of flask or reactor. The capsules fabricated in this work were easily loaded "in one step" with polymeric reagents for use as scavengers of isocyanides in the work-up process of Ugi multicomponent reactions or as compartmentalized and reusable catalysts in copper-catalyzed cycloadditions (CuAAC) or Heck palladium catalyzed cross-coupling reactions (PCCCRs). The reaction products are different series of diversely substituted isatins, which were tested in cancerous cervical HeLa and murine 3T3 Balb fibroblast cells, obtaining potent antiproliferative activity. This work demonstrates the applicability of 3D printing in chemical processes to obtain anticancer APIs.
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In this work, we prepared highly swelling, stimuli-responsive hydrogels capable of the highly efficient adsorption of inorganic pollutants. The hydrogels were based on hydroxypropyl methyl cellulose (HPMC) grafted with acrylamide (AM) and 3-sulfopropyl acrylate (SPA) and were synthesized via the growth (radical polymerization) of the grafted copolymer chains on HPMC, which was activated by radical oxidation. These grafted structures were crosslinked to an infinite network by a small amount of di-vinyl comonomer. HPMC was chosen as a cheap hydrophilic and naturally sourced polymer backbone, while AM and SPA were employed to preferentially bond coordinating and cationic inorganic pollutants, respectively. All the gels displayed a pronounced elastic character, as well as considerably high values of stress at break (several hundred %). The gel with the highest fraction of the ionic comonomer SPA (with an AM/SPA ratio = 0.5) displayed the highest equilibrium swelling ratio (12,100%), the highest volume response to temperature and pH, and the fastest swelling kinetics, but also the lowest modulus. The other gels (with AM/SPA = 1 and 2) displayed several times higher moduli but more modest pH responses and only very modest temperature sensitivity. Cr(VI) adsorption tests indicated that the prepared hydrogels removed this species from water very efficiently: between 90 and 96% in one step. The hydrogels with AM/SPA ratios of 0.5 and 1 appeared to be promising regenerable (via pH) materials for repeated Cr(VI) adsorption.
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OBJECTIVE: The aim of this study was to identify the characteristics of services in Brazil that compound the Brazilian Pediatric Palliative Care (PPC) Network. METHODS: An online survey was conducted among representatives from PPC services. A total of 90 services from Brazil completed the online survey and answered a questionnaire about the service's characterization, health professionals working in PPC, access to opioid prescription and education, and research in PPC. RESULTS: In total, 80 services (88.9%) were created after 2010, 52 (57.9%) were in the southeast region, 56 (62.2%) were in public hospitals, 63 (70%) had up to 100 beds, and 57 (63.3%) were at the tertiary level. Notably, 88 (97.8%) had a physician in the team and 68 (75.5%) dedicated part-time to PPC. Also, 33 (36.7%) revealed concern with the care of health professionals and 36 (40%) reported difficulty or no access to opioid prescription. Research studies were reported to be conducted in 29 (32.2%) services. CONCLUSIONS: This mapping points out to a concentration of PPC services in the southeast region, with part-time professional dedication, and the need to improve professionals' care. Difficulty in opioid access was reported. It is necessary to extend PPC participation to other Brazilian regions, increase time dedicated to PPC, improve professionals' care and improve access to opioid prescription.
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Cuidados Paliativos , Médicos , Niño , Humanos , Brasil , Analgésicos Opioides/uso terapéutico , Encuestas y CuestionariosRESUMEN
Abstract Objective: The aim of this study was to identify the characteristics of services in Brazil that compound the Brazilian Pediatric Palliative Care (PPC) Network. Methods: An online survey was conducted among representatives from PPC services. A total of 90 services from Brazil completed the online survey and answered a questionnaire about the service's characterization, health professionals working in PPC, access to opioid prescription and education, and research in PPC. Results: In total, 80 services (88.9%) were created after 2010, 52 (57.9%) were in the southeast region, 56 (62.2%) were in public hospitals, 63 (70%) had up to 100 beds, and 57 (63.3%) were at the tertiary level. Notably, 88 (97.8%) had a physician in the team and 68 (75.5%) dedicated part-time to PPC. Also, 33 (36.7%) revealed concern with the care of health professionals and 36 (40%) reported difficulty or no access to opioid prescription. Research studies were reported to be conducted in 29 (32.2%) services. Conclusions: This mapping points out to a concentration of PPC services in the southeast region, with part-time professional dedication, and the need to improve professionals' care. Difficulty in opioid access was reported. It is necessary to extend PPC participation to other Brazilian regions, increase time dedicated to PPC, improve professionals' care and improve access to opioid prescription.
RESUMO Objetivo: Identificar as características dos serviços que compõem a Rede Brasileira de Cuidados Paliativos Pediátricos (CPP). Métodos: Estudo do tipo survey online entre representantes de serviços de CPP. O total de 90 serviços do Brasil participaram da pesquisa e responderam a um questionário sobre a caracterização do serviço, os profissionais de saúde que nele atuam, o acesso à prescrição de opioides e a educação e pesquisa em CPP. Resultados: Oitenta serviços (88,9) foram criados após 2010, 52 (57,9%) estão na Região Sudeste, 56 (62,2%) em hospitais públicos, 63 (70%) têm até cem leitos e 57 (63,3%) estão no nível terciário. Oitenta e oito serviços (97,8%) tinham um médico na equipe e, em 68 (75,5%), os profissionais dedicavam parte de seu tempo aos CPP. Trinta e três serviços (36,7%) revelaram preocupação com o atendimento aos profissionais de saúde. Trinta e seis (40%) relataram dificuldade ou nenhum acesso à prescrição de opioides. Foi reportada a realização de pesquisas em 29 (32,2%). Conclusões: Este mapeamento aponta para a concentração dos serviços de CPP na Região Sudeste, com dedicação parcial dos profissionais, e para a necessidade de cuidar deles. Foi relatada dificuldade no acesso aos opioides. É necessário estender a participação na rede de CPP para outras regiões do Brasil, aumentar o tempo dedicado aos CPP pelos profissionais e cuidar destes, além de melhorar o acesso à prescrição de opioides.
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Triatoma melanica is a sylvatic vector species in Brazil. In We aimed to characterize the Trypanosoma cruzi discrete typing units (DTUs), the parasitic loads, and the blood meal sources of insects collected in rocky outcrops in rural areas in the state of Minas Gerais. An optical microscope (OM) and kDNA-PCR were used to examine natural infection by T. cruzi, and positive samples were genotyped by conventional multilocus PCR. Quantification of the T. cruzi load was performed using qPCR, and the blood meal sources were identified by Sanger sequencing the 12S rRNA gene. A total of 141 T. melanica were captured. Of these, ~55% (61/111) and ~91% (63/69) were positive by OM and KDNA-PCR, respectively. We genotyped ~89% (56/63) of the T. cruzi-positive triatomines, with TcI (~55%, 31/56) being the most prevalent DTU, followed by TcIII (~20%, 11/56) and TcII (~7%, 4/56). Only TcI+TcIII mixed infections were detected in 10 (~18%) specimens. A wide range of variation in the parasitic loads of T. melanica was observed, with an overall median value of 104 parasites/intestine, with females having higher T. cruzi loads than N2, N4, and N5. TcII showed lower parasitic loads compared to TcI and TcIII. The OM positive diagnosis odds ratio between T. cruzi infection when the parasite load is 107 compared to 103 was approximately 29.1. The most frequent blood meal source was Kerodon rupestris (~58%), followed by Thrichomys apereoides (~18%), Wiedomys cerradensis (~8%), Galactis cuja (~8%) and Gallus gallus (~8%). Our findings characterize biological and epidemiological aspects of the sylvatic population of T. melanica in the study area, highlighting the need to extend surveillance and control to this vector.
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Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.