Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.

Lead to hit ruthenium-cyclopentadienyl anticancer compounds: Cytotoxicity against breast cancer cells, metabolic stability and metabolite profiling.

The successful choice of hit compounds during drug development programs involves the integration of structure-activity relationship (SAR) studies with pharmacokinetic determinations, including metabolic stability assays and metabolite profiling. A panel of nine ruthenium-cyclopentadienyl (RuCp) compounds with the general formula [Ru(η5-C5H4R)(PPh3)(bipyR')]+ (with R = H, CHO, CH2OH; R' = H, CH3, CH2OH, CH2Biotin) has been tested against hormone-dependent MCF-7 and triple negative MDA-MB-231 breast cancer cells. In general, all compounds showed important cytotoxicity against both cancer cell lines and were able to inhibit the formation of MDA-MB-231 colonies in a dose-dependent manner, while showing selectivity for cancer cells over normal fibroblasts. Among them, four compounds stood out as lead structures to be further studied. Cell distribution assays revealed their preference for the accumulation at cell membrane (Ru quantification by ICP-MS) and the mechanism of cell death seemed to be mediated by apoptosis. Potential structural liabilities of lead compounds were subsequently flagged upon in vitro metabolic stability assays and metabolite profiling. The implementation of this integrated strategy led to the selection of RT151 as a promising hit compound.

Exploiting click-chemistry: backbone post-functionalisation of homoleptic gold(I) 1,2,3-triazole-5-ylidene complexes.

The synthesis of a homoleptic azide-functionalised Au(I) bis-1,2,3-triazole-5-ylidene complex is reported, starting from a backbone-modified 1,2,3-triazolium salt ligand precursor. The incorporated azide handle allows for a straightforward modification of the complex according to click-chemistry protocols without impacting the steric shielding around the metal center, demonstrating the superiority of the presented triazole ligand framework over imidazole based systems. Employing the SPAAC and the CuAAC reactions, post-modification of the complex is facilitated with two model substrates, while retaining very high antiproliferative activity (nanomolar range IC50 values) in A2780 and MCF-7 human cancer cells.

The Effects of Stress on Hippocampal Neurogenesis and Behavior in the Absence of Lipocalin-2.

Lipocalin-2 (LCN2) is an acute phase protein able to bind iron when complexed with bacterial siderophores. The recent identification of a mammalian siderophore also suggested a physiological role for LCN2 in the regulation of iron levels and redox state. In the central nervous system, the deletion of LCN2 induces deficits in neural stem cells proliferation and commitment, with an impact on the hippocampal-dependent contextual fear discriminative task. Additionally, stress is a well-known regulator of cell genesis and is known to decrease adult hippocampal cell proliferation and neurogenesis. Although voluntary running, another well-known regulator of neurogenesis, is sufficient to rescue the defective hippocampal neurogenesis and behavior in LCN2-null mice by promoting stem cells' cell cycle progression and maturation, the relevance of LCN2-regulated hippocampal neurogenesis in response to stress has never been explored. Here, we show a lack of response by LCN2-null mice to the effects of chronic stress exposure at the cellular and behavioral levels. Together, these findings implicate LCN2 as a relevant mediator of neuronal plasticity and brain function in the adult mammalian brain.

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives.

Piano-stool-{CpRu} complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA), N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA), and 3,7-dimethyl-1,3,7-triaza-5-phosphabyciclo[3.3.1]nonane (dmoPTA) were evaluated as drugs against breast cancer. The evaluated compounds include two new examples of this family, the complexes [RuCp(DMSO-κS)(HdmoPTA)(PPh3)](CF3SO3)2 (8) and [RuCp(PPh3)2-µ-dmoPTA-1κP-2κ2N,N'-PdCl2](CF3SO3) (11), which have been synthesized and characterized by NMR, IR, and single-crystal X-ray diffraction. The cytotoxic activity of compounds was evaluated against MDA-MB-231 breast cancer cells, and the three most active complexes were further tested against the hormone-dependent MCF-7 breast cancer cell line. Their cell death mechanism and ruthenium uptake were also evaluated, as well as their binding ability to human serum albumin.

Relações de amizade nos transtornos alimentares: revisão integrativa da literatura / Friendship relationships in eating disorders: an integrative literature review / Relaciones de amistad en los trastornos alimentarios: revisión integradora

Ainda é desconhecido o papel da amizade enquanto constitutiva da rede de apoio social nos transtornos alimentares (TAs). Esta revisão integrativa teve por objetivo analisar a produção científica sobre relações de amizade em pessoas com TAs. Foram consultadas as bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, de 2010 a 2020. Dos 1126 artigos recuperados, 15 preencheram os critérios de elegibilidade. A maioria tem abordagem qualitativa e delineamento transversal, sem indicar referencial teórico. Aspectos qualitativos das relações de amizade foram associados com redução da frequência e intensidade de sintomas quando o vínculo era considerado de boa qualidade. Já amizades que envolviam comentários depreciativos e influências negativas acerca do corpo e hábitos alimentares foram considerados fatores de risco para desencadeamento dos transtornos. Investir na qualidade dos relacionamentos entre pares pode contribuir para fortalecer a rede de proteção social e reduzir a vulnerabilidade psicossocial de adolescentes com risco para desenvolver TAs. (AU)

There is still little knowledge about the role of friendship within the social support network in eating disorders (EDs). This integrative review aimed to analyze the scientific production about friendship relationships in people with EDs. The literature review was conducted using the PubMed/MEDLINE, LILACS, PsycINFO, Web of Science, and EMBASE databases in the period from 2010 to 2020. Among the 1126 articles retrieved, 15 met the eligibility criteria, most with a qualitative approach and cross-sectional design, without indicating a theoretical framework. The qualitative aspects of friendship were associated with a reduced frequency and intensity of symptoms when the bond was considered to be of good quality. On the other hand, friendships that involved derogatory comments and negative influences related to body image and eating habits emerged as potential risk factors for triggering disorders. Investing in the quality of peer relationships can contribute to strengthening the social safety net and reducing the psychosocial vulnerability of adolescents at higher risk for developing EDs. (AU)

El papel de la amistad como constitutiva de la red de apoyo social en los trastornos alimentarios (TAs) es aún desconocido. Este estudio tiene como objetivo analizar la producción científica sobre las relaciones de amistad en personas con TAs. Se consultaron las bases PubMed/MEDLINE, LILACS, PsycINFO, Web of Science e EMBASE, entre 2010 y 2020. De los 1126 artículos recuperados, 15 cumplían los criterios de elegibilidad. La mayoría tiene enfoque cualitativo y diseño transversal, sin indicar el marco teórico. Los aspectos cualitativos de las relaciones de amistad se asociaron con una menor frecuencia/intensidad de los síntomas cuando el vínculo se consideraba de buena calidad. Amistades que implicaban comentarios despectivos e influencias negativas sobre el cuerpo y los hábitos alimentarios se consideraron factores de riesgo. Invertir en la calidad de las relaciones entre pares puede contribuir a reforzar la red de protección social y reducir la vulnerabilidad de adolescentes con riesgo de desarrollar TAs. (AU)

Copper(I)-Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity.

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4 ], in which PP is a phosphane ligand (triphenylphosphane or 1,2-bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4-(methyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti-trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Antitumoral and Antimicrobial Activities of Block Copolymer Micelles Containing Gold Bisdithiolate Complexes.

Gold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]- (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]- were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]-/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]-. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.

Cell Uptake of Steroid-BODIPY Conjugates and Their Internalization Mechanisms: Cancer Theranostic Dyes.

Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11ß-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.

Bridging the Chemical Profile and Biological Activities of a New Variety of Agastache foeniculum (Pursh) Kuntze Extracts and Essential Oil.

This study investigated the phytochemical content of alcoholic extracts and essential oil of a new variety of medicinal plants, Agastache foeniculum (Pursh), which Kuntze adapted for cultivation in Romania, namely "Aromat de Buzau". The essential oil was investigated by GC-MS, while the identification and quantification of various compounds from alcoholic extracts were performed by HPLC-DAD. The total phenol and flavonoid contents of the extracts were evaluated by using standard phytochemical methods. The antioxidant activities of ethanol, methanol extracts, and essential oil of the plant were also assessed against 2,2'-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+), and by ferric reducing power (FRAP) using spectroscopic methods. Cyclic voltammetry was used to evaluate the antioxidant capacity of the essential oil. The concentrations of phenolic compounds were higher in methanolic extract compared to ethanolic extract. A significant correlation was found between total phenol and total flavonoid contents (r = 0.9087). Significant high correlations were also found between the total phenolic compounds and the antioxidant activities of the extracts (r ≥ 0.8600, p < 0.05). In addition, the extracts and essential oil showed good antioxidant and xanthine oxidase inhibitory activities. Estragole was detected as the major constituent of the essential oil (94.89%). The cytotoxic activity of the essential oil was evaluated by the MTT assay. At lower concentrations (1 µg/mL) high cytotoxicity against MCF-7 breast cancer cells was observed but not on the non-tumoral dermal fibroblasts (HDF) which indicated selectivity for cancer cells and suggests the presence of biologically active components that contribute to the observed high cytotoxic effect. Findings from the present study offer new perspectives on the use of A. foeniculum as a potential source of bioactive compounds and a good candidate for pharmaceutical plant-based products.

Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors.

Over the last decades, gold nanoparticles (AuNPs) have proven to be remarkable tools for drug delivery and theranostic applications in cancer treatment. On the other hand, Pt(IV) prodrugs have been employed as an interesting alternative to the more common Pt(II) complexes, such as cisplatin, for cancer chemotherapy. Searching to design an image-guided nanocarrier to deliver selectively Pt(IV) prodrugs to tumors expressing the gastrin releasing peptide receptor (GRPR), we have synthesized small core AuNPs carrying a thiolated DOTA derivative, a GRPR-targeting bombesin analog (BBN[7-14]) and a Pt(IV) prodrug attached to the AuNPs without (AuNP-BBN-Pt1) or with a PEGylated linker (AuNP-BBN-Pt2 and AuNP-BBN-Pt3). In the GRPR+ prostate cancer PC3 cell line, the cytotoxic activity of the designed AuNP-BBN-Pt nanoparticles is strongly influenced by the presence of the PEGylated linker. Thus, AuNP-BBN-Pt1 displayed the lowest IC50 value (9.3 ± 2.3 µM of Pt), which is comparable to that exhibited by cisplatin in the same cell line. In contrast, AuNP-BBN-Pt1 showed an IC50 value of 97 ± 18 µM of Pt in the non-tumoral RWPE-1 prostate cells with a much higher selective index (SI) towards PC3 cells (SI = 10) when compared with cisplatin (SI = 1.3). The AuNPs were also successfully labeled with 67Ga and the resulting 67Ga-AuNP-BBN-Pt were used to assess their cellular uptake in PC3 cells, with AuNP-BBN-Pt1 also displaying the highest cellular internalization. Finally, intratumoral administration of 67Ga-AuNP-BBN-Pt1 in a PC3 tumor-bearing mice showed a prolonged retention of the nanoparticle compared to that of cisplatin, with optimal in vivo stability and 20% of the injected platinum remaining in the tumor after 72 h post-injection. Furthermore, microSPECT imaging studies confirmed the uptake and considerable retention of the 67Ga-labeled AuNPs in the tumors. Overall, these results show the potential of these targeted AuNPs loaded with Pt(IV) prodrugs for prostate cancer theranostics.

Ruthenium(II) polypyridyl complexes with benzothiophene and benzimidazole derivatives: Synthesis, antitumor activity, solution studies and biospeciation.

With the aim to incorporate pharmacophore motifs into the Ru(II)-polypyridyl framework, compounds [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzo[b]thiophene)](CF3SO3)2 (1) and [Ru(II)(1,10-phenantroline)2(2-(2-pyridyl)benzimidazole)](CF3SO3)2 (2) were prepared, characterized and tested for their antitumor potential. The solid-state structure of the compounds was confirmed by single-crystal X-ray diffraction analysis. The solution behavior of both complexes was investigated, namely their solubility, stability, and lipophilicity in physiological mimetic conditions, as well as an eventual uptake by passive diffusion. In vitro anticancer activity of the complexes on ovarian and different colon cancer cells and apoptosis induction by the complexes were studied. A slow transformation process was observed for complex 1 in aqueous solution when exposed to sunlight, while complex 2 undergoes deprotonation (pKa = 7.59). The lipophilicity of this latter complex depends strongly on the pH and ionic strength. In contrast, 1 is rather hydrophilic under various conditions. Complex 1 was highly cytotoxic on Colo-205 human colon (IC50 = 7.87 µM) and A2780 ovarian (IC50 = 2.2 µM) adenocarcinoma cell lines, while 2 displayed moderate anticancer activity (30.9 µM and 18.0 µM, respectively). The complexes induced late apoptosis and necrosis. Only a weak binding of the complexes to human serum albumin, the main transport protein in blood serum, was found. However, a more significant binding to calf thymus DNA was observed in UV-visible titrations and fluorometric dye displacement studies. Detailed analysis of fluorescence lifetime data collected for the latter systems reveals not only the partial intercalation of the complexes, but goes beyond the usual simplified interpretations.

Estratégias de enfrentamento utilizadas por crianças com câncer em tratamento quimioterápico / Estrategias de enfrentamiento utilizadas por niños con cáncer en tratamiento quimioterápico / Coping strategies used by children with cancer in chemotherapy treatment

RESUMO Objetivo: identificar as estratégias de enfrentamento utilizadas por crianças com câncer diante de uma situação difícil antes e após intervenção com jogo de tabuleiro. Método: Trata-se de um estudo de intervenção, realizado no ambulatório de quimioterapia de um centro de tratamento especializado em oncologia pediátrica de Mato Grosso do Sul. A amostra foi composta por 10 crianças de 7 a 12 anos em tratamento quimioterápico. Para a coleta de dados foi aplicada a escala Kidcope - versão infantil brasileira, antes e após a intervenção com o jogo de tabuleiro "Skuba! Uma aventura no fundo do mar". Para a análise dos dados, utilizou-se estatística descritiva e inferencial. Resultados: as situações difíceis referidas pelas crianças foram de natureza pessoal e envolviam procedimentos invasivos durante o tratamento. Evidenciou-se o uso de estratégias de enfrentamento de evitação, como distração e pensamento mágico. As crianças revelaram, quanto ao uso das estratégias, que tentavam esquecer a situação difícil, através de atividades de distração, como assistir à televisão ou jogar um jogo, e não ficar sozinhas, evitando assim o isolamento social. Conclusão: as estratégias de enfrentamento utilizadas pelas crianças com câncer, mediadas pela intervenção com o jogo de tabuleiro, foram de evitação, com o predomínio da distração.

RESUMEN Objetivo: identificar las estrategias de enfrentamiento utilizadas por niños con cáncer ante una situación difícil antes y después de la intervención con juego de mesa. Método: se trata de un estudio de intervención, realizado en el ambulatorio de quimioterapia de un centro de tratamiento especializado en oncología pediátrica de Mato Grosso do Sul-Brasil. La muestra fue compuesta por 10 niños de 7 a 12 años en tratamiento quimioterápico. Para la recolección de datos se aplicó la escala Kidcope - versión infantil brasileña, antes y después de la intervención con el juego de mesa "¡Skuba! Una aventura en el fondo del mar". Para el análisis de los datos, se utilizó estadística descriptiva e inferencial. Resultados: las situaciones difíciles relatadas por los niños fueron de naturaleza personal e involucraban procedimientos invasivos durante el tratamiento. Se evidenció el uso de estrategias de enfrentamiento de evitación, como distracción y pensamiento mágico. Los niños revelaron, en cuanto al uso de las estrategias, que intentaban olvidar la situación difícil, a través de actividades de distracción, como ver la televisión o jugar un juego, y no quedarse solos, evitando así el aislamiento social. Conclusión: las estrategias de enfrentamiento utilizadas por los niños con cáncer, mediadas por la intervención con el juego de mesa, fueron de evitación, con el predominio de la distracción.

ABSTRACT Objective: to identify coping strategies used by children with cancer in the face of a difficult situation before and after intervention with a board game. Method: this is an intervention study, conducted in the outpatient chemotherapy of a treatment center specialized in pediatric oncology in Mato Grosso do Sul. The sample consisted of 10 children aged 7 to 12 years undergoing chemotherapy. For data collection was applied the Kidcope scale - Brazilian children's version, before and after the intervention with the board game "Skuba! An adventure on the seabed". For data analysis, descriptive and inferential statistics were used. Results: the difficult situations reported by the children were of a personal nature and involved invasive procedures during treatment. The use of avoidance coping strategies, such as distraction and magical thinking, was evidenced. The children revealed, regarding the use of strategies that they tried to forget the difficult situation, through distraction activities, such as watching television or playing a game, and not being alone, thus avoiding social isolation. Conclusion: the coping strategies used by children with cancer, mediated by the intervention with the board game, were avoidance, with the predominance of distraction.

Health-related quality of life in children with cerebral palsy associated with congenital Zika infection / Qualidade de vida relacionada à saúde em crianças com paralisia cerebral associada a síndrome da Zika congênita

Abstract Objective: To describe the health-related quality of life (QOL) in children with cerebral palsy (CP) associated with congenital Zika infection. Methods: Cross-sectional study of a consecutive series of children, followed in a referral multicentric rehabilitation network in Brazil. We invited the caregivers to respond to the Brazilian version of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILDTM) questionnaire. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) 26.0™. We used absolute and relative frequencies for categorical variables and mean and standard deviation for continuous variables. Results: The sample consisted of 193 children, at mean age of 50.3±7.6 months. We observed a predominance of children with cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level V (93.7%). Epilepsy (88.4%) was the most common comorbidity. CPCHILDTM mean scores were activities of daily living (ADL)/personal care 43.2±12.6; positioning, transferring and mobility 33.7±16.5; comfort and emotions 84.4±15.2; communication and social interaction (CoSI) 48.2±24.3; health 70.9±17.1; and overall quality of life (OQOL) 72.1±17.1. Total score was 54.8±11.3. Conclusions: Among children with cerebral palsy (CP) related to congenital Zika syndrome, the quality of life (QOL) scores were very similar to other populations with cerebral palsy (CP). The activities of positioning, transferring and mobility had the greatest impact on health-related quality of life (QOL). Rehabilitation strategies and public policies should prioritize aspects related to mobility for this population.

RESUMO Objetivo: Descrever a qualidade de vida relacionada à saúde em crianças com paralisia cerebral associada à infecção congênita pelo zika. Métodos: Estudo transversal de série consecutiva de casos de crianças acompanhadas em uma rede multicêntrica de reabilitação no Brasil. Convidamos o(s) cuidador(es) a responder à versão brasileira do Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILDTM). A análise estatística foi realizada com o pacote estatístico Statistical Package for the Social Sciences (SPSS) 26.0™. Para variáveis categóricas, foram utilizadas frequências absolutas e relativas e, para variáveis contínuas, média e desvio padrão. Resultados: Cento e noventa e três crianças, com idade média de 50,3±7,6 meses, foram incluídas. Observou-se predomínio de crianças com paralisia cerebral Gross Motor Function Classification System (GMFCS) nível V (93,7%). Epilepsia (88,4%) foi a comorbidade mais comum. As pontuações médias do CPCHILDTM foram: atividades de vida diária/cuidados pessoais 43,2±12,6; posicionamento, transferência e mobilidade 33,7±16,5; conforto e emoções 84,4±15,2; comunicação e interação social 48,2±24,3; saúde 70,9±17,1; e qualidade de vida geral 72,1±17,1. A pontuação total foi 54,8±11,3. Conclusões: Entre as crianças com paralisia cerebral relacionada à síndrome do zika congênita, as atividades de posicionamento, transferência e mobilidade tiveram maior impacto na qualidade de vida relacionada à saúde, semelhantemente a outras etiologias de paralisia cerebral. As estratégias de reabilitação e as políticas públicas devem priorizar os aspectos relacionados à mobilidade dessa população.

Crianças e adolescentes com necessidades especiais de saúde: o cuidado nos serviços de atenção domiciliar / Niños y adolescentes con necesidades especiales de salud: cuidado en los servicios de atención a domicilio / Children and adolescents with special healthcare needs: care in home care services

RESUMO Objetivo descrever o cuidado prestado às crianças com necessidades especiais de saúde nos Serviços de Atenção Domiciliar do estado de Mato Grosso do Sul. Métodos pesquisa quantitativa, descritiva e exploratória. Os participantes do estudo foram profissionais dos Serviços de Atenção Domiciliar do Mato Grosso do Sul. A coleta de dados se deu com a aplicação de dois formulários on-line, no período de 2019 a 2020. Um dos formulários tinha dados descritivos dos serviços e seus atendimentos; o outro se voltava para a validação de protocolo de fluxo de atenção domiciliar às crianças. Para análise de dados, utilizou-se a estatística descritiva. Resultados houve uma predominância de 25 crianças com paralisia cerebral, sendo que a maioria foi classificada como média complexidade, de acordo com a complexidade e as demandas de cuidados. Os profissionais realizam orientações, procedimentos e avaliação, além de serem responsáveis pelo treinamento da família. Os serviços não possuem protocolo de fluxo para atendimento das crianças. Conclusão Implicações para Prática embora os serviços apresentem capacidade de ampliação do atendimento e utilizem o Plano Terapêutico Singular, avanços na assistência às crianças e famílias ainda se fazem necessários. Recomenda-se a elaboração de protocolos de fluxo e propostas organizativas que auxiliem os profissionais em sua prática.

RESUMEN Objetivo Descrever a atención prestada a niños con necesidades especiales de salud en los Servicios de Atención Domiciliaria del Estado de Mato Grosso do Sul. Métodos investigação cuantitativa, descritiva e exploratoria. Los participantes del estudio fueron profesionales de los servicios de atención domiciliaria de Mato Grosso do Sul. La recolección de datos ocurrió a través de la aplicación de dos formularios en línea, de 2019 a 2020, uno con datos descriptivos de los servicios y su atención y el otro para la validación del protocolo para el flujo de atención domiciliaria a los niños. Se utilizó estadística descriptiva para el análisis de datos. Resultados hubo un predominio de 25 niños con parálisis cerebral. La mayoría clasificó como mediana complejidad de acuerdo a la complejidad y demandas de atención. The professionals carry out lineamientos, procedures, evaluation and are responsible for training the family. Los servicios no cuentan con un protocolo de flujo para la atención de niños. Conclusion Implications for Practice Although the services have the capacity to expand care and use the Singular Therapeutic Plan, advances in the care of the child and the family are still needed. The development of flow protocols and organizational proposals that help professionals in their practice are recommended.

ABSTRACT Objective to describe the care provided to children with special health needs in the Home Care Services of the State of Mato Grosso do Sul - Brazil. Methods research, descriptive and exploratory. Study participants were professionals from home care services in Mato Grosso do Sul. Data collection took place through the application of two online forms, from 2019 to 2020, one containing descriptive data of the services and their care and the other for validation of the home care flow protocol for children. It was used for data analysis and descriptive statistics. Results there was a predominance of 25 children with brain flexibility. Most classified as complex average according to the complexity and demands of care. Professionals and guidelines, procedures, assessment are responsible for training the family. The services do not have a flow protocol for the care of children. Conclusion Implications for Practice Services Present ability to deliver care and use the care plan and single use, advances in child care and solutions may still be presented. There is a practice of elaborating flow protocols and organization proposals that help professionals in their.

Telas na infância: postagens de especialistas em grupos de cuidadores no facebook / Screens in childhood: posts of specialists in caretakers' groups in the facebook / Pantallas en la infancia: las publicaciones de expertos en grupos de cuidadores en facebook

Apesar das crescentes investigações sobre uso de telas na infância, essa é uma temática complexa e ainda recente, que traz diversos desafios para pesquisadores e cuidadores. Comunidades virtuais em redes sociais são utilizadas por mães e pais para esclarecer dúvidas e receber conselhos acerca da parentalidade e saúde infantil, podendo, simultaneamente, assumir uma função prescritiva e normativa quanto ao seu modo de agir. Sendo assim, este artigo pretende compreender como o uso de telas na infância vem sendo abordado por especialistas em grupos de mães e pais no Facebook. Foi realizado um estudo qualitativo envolvendo 49 postagens de especialistas, sobretudo psicólogos e educadores, extraídas de cinco grupos públicos de mães e pais nessa rede social. Os textos das publicações foram verificados por meio de análise temática e discutidos com base no referencial teórico psicanalítico. Os resultados mostraram que os especialistas destacam os possíveis prejuízos do uso de telas na infância, além de fornecer orientações aos pais sobre como lidar com sua presença no cotidiano das crianças e de suas famílias. Concluiu-se que apesar dos grupos de cuidadores no Facebook serem uma ferramenta de divulgação de informações acerca do uso de telas na infância, cabe não naturalizar a presença de especialistas nesses espaços virtuais criados por pais e mães, interpondo-se nos saberes e nas trocas horizontalizadas entre os cuidadores.(AU)

Although investigations on the use of screens in childhood are increasing, this is a complex and recent topic, which poses several challenges for researchers and caregivers. Virtual communities in social networks are used by mothers and fathers to clarify doubts and receive advice regarding parenting and child health, at times, simultaneously, assuming a prescriptive and normative role on their way of acting. Therefore, this study aimed to understand how the use of screens in childhood has been approached by experts in groups of mothers and fathers on Facebook. A qualitative study was carried out involving 49 posts from specialists, mainly psychologists and educators, extracted from five public groups of mothers and fathers in this social network. The publications' texts were verified via thematic analysis and discussed based on the psychoanalytical theoretical framework. The results showed that experts highlight the possible damage of the use of screens in childhood, in addition to providing guidance to parents on how to deal with the presence of digital technology in the daily lives of children and families. It was concluded that, although caregivers' groups on Facebook are a tool for disseminating information about the use of screens in childhood, it is important not to naturalize the presence of specialists in these virtual spaces created by fathers and mothers, interposing in the horizontally interchanges that occur between the caregivers.(AU)

A pesar de las crecientes investigaciones sobre el uso de pantallas en la infancia, este es un tema complejo y aún reciente, que plantea varios desafíos para investigadores y cuidadores. Las comunidades virtuales en las redes sociales son utilizadas por madres y padres para aclarar dudas y recibir consejos sobre educación y salud infantil, pudiendo, al mismo tiempo, asumir un rol prescriptivo y normativo sobre su forma de actuar. Por lo tanto, este estudio tuvo como objetivo comprender cómo el uso de las pantallas en la infancia ha sido abordado por especialistas en grupos de madres y padres en Facebook. Se realizó un estudio cualitativo a partir de 49 publicaciones de especialistas, principalmente de psicólogos y educadores, extraídas de cinco grupos públicos de madres y padres en esta red social. Se realizó en los textos de las publicaciones un análisis temático y se utilizó el marco teórico psicoanalítico. Los resultados mostraron que los expertos destacan posibles daños que provoca el uso de pantallas en la infancia, además de orientar a los padres sobre cómo afrontar esta presencia de la tecnología digital en el día a día de los niños y sus familias. Se concluyó que, a pesar de que los grupos de cuidadores en Facebook son una herramienta de difusión de información sobre el uso de pantallas en la infancia, es importante no naturalizar la presencia de especialistas en estos espacios virtuales creados por padres y madres que se interpone entre los saberes e intercambios horizontales de los cuidadores.(AU)

O desbravar de novos caminhos: itinerário terapêutico de famílias de crianças e adolescentes com câncer / Abriendo nuevos caminos: el itinerario terapéutico de las familias de niños y adolescentes con cáncer / Breaking new paths: therapeutic itinerary of families of children and adolescents with cancer

Objetivos: descrever o itinerário terapêutico de crianças/adolescentes com câncer e suas famílias. Método: estudo descritivo qualitativo realizado com 11 mães e uma avó de crianças/adolescentes em tratamento de câncer, guiado pelo referencial teórico do Modelo de Sistemas de Cuidados à Saúde. Os dados foram coletados no período de março a setembro de 2019, por meio de entrevistas semiestruturadas e audiogravadas, submetidas à análise de conteúdo de Morse e Field. Resultados: para a família, o caminho percorrido durante todo o processo de busca pelo diagnóstico e pela cura se configurou em sofrimento e sentimentos ambíguos. Ao longo do itinerário terapêutico, cada família estabeleceu seu modo de agir, perceber, se comunicar, de se relacionar e tomar decisões. Considerações finais: conhecer o itinerário terapêutico de famílias de crianças/adolescentes com câncer pode nortear intervenções de enfermagem assertivas e subsidiar a elaboração de estratégias que aprimorem o diagnóstico precoce da doença, favorecendo o melhor prognóstico.

Objetivos: describir el itinerario terapéutico de niños/adolescentes con cáncer y sus familias. Método: se trata de un estudio descriptivo cualitativo realizado entre 11 madres y una abuela de niños/adolescentes bajo tratamiento de cáncer, guiado por el referencial teórico del Modelo de Sistemas de Cuidados de la Salud. Los datos se recopilaron durante el período comprendido entre marzo y septiembre de 2019, mediante entrevistas semiestructuradas y audio-grabadas, sometidas al análisis de contenido de Morse y Field. Resultados: para la familia, el camino recorrido a lo largo del proceso de búsqueda de un diagnóstico y una cura se caracterizó por el sufrimiento y los sentimientos ambiguos. A lo largo del itinerario terapéutico, cada familia estableció su propia forma de actuar, percibir, comunicarse, relacionarse y tomar decisiones. Conclusión: conocer el itinerario terapéutico de las familias de niños/adolescentes con cáncer puede orientar las intervenciones asertivas de la enfermería y subsidiar el desarrollo de estrategias que mejoren el diagnóstico precoz de la enfermedad de una manera más precisa.

Objective: to describe the therapeutic itinerary of children/adolescents with cancer and their families. Method: qualitative descriptive study carried out with 11 mothers and one grandmother of children/adolescents undergoing cancer treatment, guided by the theoretical framework of the Health Care Systems Model. Data were collected from March to September 2019, through semi-structured and audio-recorded interviews, submitted to Morse and Field content analysis. Results: for the family, the path taken throughout the process of searching for diagnosis and cure was characterized by suffering and ambiguous feelings. Throughout the therapeutic itinerary, each family established their way of acting, perceiving, communicating, relating and making decisions. Final considerations: knowing the therapeutic itinerary of families of children/adolescents with cancer can guide assertive nursing interventions and support the development of strategies that improve the early diagnosis of the disease, favoring a better prognosis

Câncer infantojuvenil: conhecimentos de famílias de crianças atendidas na atenção primária à saúde / Childhood cancer: knowledge of families of children assisted in primary health care / Cáncer infantil: conocimiento de familias de niños atendidos en la atención primaria de salud

Objetivo: identificar o conhecimento das famílias de crianças atendidas na Atenção Primária à Saúde sobre os sinais e sintomas do câncer infantojuvenil. Método: estudo descritivo, qualitativo realizado com 14 familiares de crianças atendidas na Atenção Primária à Saúde. Os dados foram coletados por meio de entrevista semiestruturada realizada por intermédio de um aplicativo de mensagens simultâneas e analisados seguindo as etapas preconizadas pela Análise Qualitativa de Conteúdo. Resultados: a partir da análise dos dados, foi possível elencar duas categorias analíticas conhecimentos e percepções das famílias sobre câncer infantojuvenil e necessidades de informações sobre o câncer infantojuvenil. Conclusão: o envolvimento das famílias nas consultas de puericultura e o compartilhamento de informações por parte dos profissionais são recursos que podem facilitar o reconhecimento de sinais e sintomas de alerta para o câncer infantojuvenil, principalmente na Atenção Primária à Saúde

Objective: to identify the knowledge of the families of children assisted in Primary Health Care about the signs and symptoms of cancer in children. Method: descriptive, qualitative study carried out with 14 family members of children and adolescents assisted in Primary Health Care. Data were collected through semi-structured interviews conducted through a simultaneous messaging application and analyzed following the steps recommended by Qualitative Content Analysis. Results: it was possible to list two central categories: knowledge and perceptions of families about childhood cancer and information needs about childhood cancer. Conclusion: the involvement of families in childcare consultations and the sharing of information by professionals are resources that can facilitate the recognition of warning signs and symptoms for childhood cancer, especially in Primary Health Care

Objetivos: identificar el conocimiento de las familias de niños atendidos en la Atención Primaria de Salud sobre los signos y síntomas del cáncer en niños. Método: estudio descriptivo, cualitativo, realizado con 14 familiares de niños atendidos en la Atención Primaria de Salud. Los datos fueron recolectados a través de entrevistas semiestructuradas realizadas a través de una aplicación de mensajería simultánea y analizados siguiendo los pasos recomendados por el Análisis Cualitativo de Contenido. Resultados: fue posible enumerar dos categorías centrales: conocimientos y percepciones de las familias sobre el cáncer infantil y necesidades de información sobre el cáncer infantil. Conclusión: la participación de las familias en las consultas de puericultura y el intercambio de información por parte de los profesionales son recursos que pueden facilitar el reconocimiento de signos y síntomas de alarma del cáncer infantil, especialmente en la Atención Primaria de Salud

Interdisciplinary training for the family approach in primary healthcare / Formación interdisciplinaria para el enfoque familiar en la atención primaria de salud / A formação interdisciplinar para a abordagem familiar na atenção primária à saúde

ABSTRACT Objective: To reflect on the interdisciplinary training of health team professionals to work with the family in Primary Healthcare, considering the complexity of the family phenomenon in their health and illness experiences. Method: A reflection article in which the need to incorporate new concepts for training professionals to work with the family in Primary Healthcare is discussed. Results: The theoretical articulation between the Patient- and Family-Centered Care Model, Interprofessional Education and Primary Healthcare is fundamental to guide interdisciplinary training in health, aiming at including the family as the protagonist of the care of its members and active in the teaching and learning process of the healthcare professionals. Conclusion: It becomes necessary to promote changes in the training model of health professionals to incorporate collaborative practice with the family.

RESUMEN Objetivo: reflexionar sobre la formación interdisciplinar de los profesionales del equipo de salud para el trabajo con la familia en la Atención Primaria de Salud, considerando la complejidad del fenómeno familiar en sus vivencias de salud y enfermedad. Método: artículo de reflexión en el que se discute la necesidad de incorporar nuevos conceptos para la formación de profesionales para el trabajo con la familia en la Atención Primaria de Salud. Resultados: la articulación teórica entre el Modelo de Atención Centrado en el Paciente y la Familia, la Educación Interprofesional y la Atención Primaria de Salud es fundamental para orientar la formación interdisciplinaria en salud, visando incluir a la familia como protagonista del cuidado de sus miembros y activa en el proceso de enseñanza- aprendizaje de los profesionales. Conclusión: es necesario promover cambios en el modelo de formación de los profesionales de la salud para la incorporación de la práctica colaborativa con la familia.

RESUMO Objetivo: refletir sobre a formação interdisciplinar dos profissionais da equipe de saúde para atuar com a família na Atenção Primária à Saúde, considerando a complexidade do fenômeno família em suas experiências de saúde e doença. Método: artigo de reflexão em que se discute a necessidade de incorporar novas concepções para a formação dos profissionais para atuar com a família na Atenção Primária à Saúde. Resultados: a articulação teórica entre o Modelo do Cuidado Centrado no Paciente e na Família, a Educação Interprofissional e a Atenção Primária à Saúde é fundamental para nortear a formação interdisciplinar em saúde, visando a inclusão da família como protagonista do cuidado de seus membros e ativa no processo de ensino-aprendizagem dos profissionais. Conclusão: torna-se necessário promover mudanças no modelo de formação dos profissionais de saúde para a incorporação da prática colaborativa junto à família.