Aplicativo para rastreio de fragilidade: ferramenta de cuidado ao idoso na Atenção Primária à Saúde / Application for screening frailty: elderly care tool in Primary Health Care

Objetivo: Desenvolver aplicativo de rastreio de fragilidade em idosos na Atenção Primária à Saúde e validar, semanticamente, com profissionais de saúde. Método: Estudo metodológico, realizado de fevereiro a março de 2021, por meio de validação semântica, com 75 enfermeiros e 44 médicos da Estratégia Saúde da Família dos 25 municípios da 2ª Região de Saúde do Estado da Paraíba e construção de aplicativo móvel denominado APS para Idosos Frágeis, para uso em sistema Android, com linguagem de programação HTML, Java Script, CSS, PHP, Framework IONIC e modelo de produção MVC. Resultado: Entre as 42 variáveis presentes no instrumento de validação semântica foram selecionadas 20 variáveis para compor o aplicativo, formado por quatro Dimensões: Fisiológica, Funcional, Biopsicossocial, Cognitiva. Conclusão: O aplicativo possibilita a avaliação multidimensional do idoso na Atenção Primária à Saúde. Entende-se que o diagnóstico precoce da fragilidade proporciona estabilização do quadro clínico, diminuindo risco de hospitalização, morte e encaminhamentos para atenção especializada.

Objectives: To develop an application for screening frailty in the elderly in Primary Health Care and to validate it semantically with health professionals. Methods: Methodological study, carried out from February to March 2021, through semantic validation. With the participation of 75 nurses and 44 doctors of the Family Health Strategy from the 25 Municipalities of the Second Health Region of the State of Paraíba. In addition to the construction of a mobile application called Primary Health Care for frail elderly, for use on an Android system, with the programming language HTML, Java Script, CSS, PHP, Framework IONIC and MVC production model. Results: Among the 42 variables present in the semantic validation instrument, 20 variables were selected to compose the application, formed by four Dimensions: Physiological, Functional, Biopsychosocial, Cognitive. Conclusion: The application enables the multidimensional assessment of the elderly in primary health care. It was identified that the early diagnosis of frailty provides stabilization of the clinical condition, reducing the risk of hospitalization, death and referrals to specialized care.

A Systematic Review of CrossFit® Workouts and Dietary and Supplementation Interventions to Guide Nutritional Strategies and Future Research in CrossFit®.

CrossFit® is a high-intensity functional training method consisting of daily workouts called "workouts of the day." No nutritional recommendations exist for CrossFit® that are supported by scientific evidence regarding the energetic demands of this type of activity or dietary and supplement interventions. This systematic review performed in accordance with PRISMA guidelines aimed to identify studies that determined (a) the physiological and metabolic demands of CrossFit® and (b) the effects of nutritional strategies on CrossFit® performance to guide nutritional recommendations for optimal recovery, adaptations, and performance for CrossFit® athletes and direct future research in this emerging area. Three databases were searched for studies that investigated physiological responses to CrossFit® and dietary or supplementation interventions on CrossFit® performance. Various physiological measures revealed the intense nature of all CrossFit® workouts of the day, reflected in substantial muscle fatigue and damage. Dietary and supplementation studies provided an unclear insight into effective strategies to improve performance and enhance adaptations and recovery due to methodological shortcomings across studies. This systematic review showed that CrossFit® is a high-intensity sport with fairly homogenous anaerobic and aerobic characteristics, resulting in substantial metabolic stress, leading to metabolite accumulation (e.g., lactate and hydrogen ions) and increased markers of muscle damage and muscle fatigue. Limited interventional data exist on dietary and supplementation strategies to optimize CrossFit® performance, and most are moderate to very low quality with some critical methodological limitations, precluding solid conclusions on their efficacy. High-quality work is needed to confirm the ideal dietary and supplemental strategies for optimal performance and recovery for CrossFit® athletes and is an exciting avenue for further research.

Sonography of the distal femoral epiphysis in the etiological diagnosis of congenital hypothyroidism.

The etiology of congenital hypothyroidism (CH) is often difficult to identify, owing mainly to limitations in currently available diagnostic tests. Characteristics of the distal femoral epiphyseal (DFE) ossification center may provide important information and help identify some causes of CH. We analyzed the contribution of DFE ultrasonography in the investigation of 11 young infants with positive screening for CH. DFE ultrasonography emerged as a simple test that helped indicate the period of onset of CH and, when associated with clinical history, hormone levels, and thyroid ultrasonography, contributed to suggest the etiology of CH.

Genistein protects hematopoietic stem cells against G-CSF-induced DNA damage.

Granulocyte colony-stimulating factor (G-CSF) has been used to treat neutropenia in various clinical settings. Although clearly beneficial, there are concerns that the chronic use of G-CSF in certain conditions increases the risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The most striking example is in severe congenital neutropenia (SCN). Patients with SCN develop MDS/AML at a high rate that is directly correlated to the cumulative lifetime dosage of G-CSF. Myelodysplastic syndrome and AML that arise in these settings are commonly associated with chromosomal deletions. We have demonstrated in this study that chronic G-CSF treatment in mice results in expansion of the hematopoietic stem cell (HSC) population. In addition, primitive hematopoietic progenitors from G-CSF-treated mice show evidence of DNA damage as demonstrated by an increase in double-strand breaks and recurrent chromosomal deletions. Concurrent treatment with genistein, a natural soy isoflavone, limits DNA damage in this population. The protective effect of genistein seems to be related to its preferential inhibition of G-CSF-induced proliferation of HSCs. Importantly, genistein does not impair G-CSF-induced proliferation of committed hematopoietic progenitors, nor diminishes neutrophil production. The protective effect of genistein was accomplished with plasma levels that are attainable through dietary supplementation.

Thymoma originating in a giant thymolipoma: a rare intrathoracic lesion.

Thymolipoma is a rare, slow-growing, benign tumor that arises from the anterior mediastinum and corresponds to 2% to 9% of all thymic neoplasms. We present the case of a 49-year-old man who had a large heterogeneous mass with areas of soft tissue and fat tissue located on the anterior mediastinum and right hemithorax. After resection, histologic analysis confirmed the diagnosis of a giant thymolipoma containing solid components that corresponded to thymomas B1, B2, and B3. We discuss the occurrence of an atypical variant of thymolipoma containing three types of thymomas inside.

Modalidades de violência vivenciadas por mulheres atendidas numa Unidade de Saúde da Família Integrada / Terms of violence experienced by women attended at a Unit of Health of Integrated Family

Objetivo: investigar as modalidades de violência de gênero praticadas contra as mulheres cadastradas naatenção básica. Método: estudo exploratório, com abordagem quantitativa. Os dados foram coletados portécnica de entrevista numa Unidade de Saúde da Família Integrada em João Pessoa/PB/Nordeste do Brasilcom 400 mulheres. A análise estatística descritiva foi realizada pelo cálculo de medidas de tendência centrale de dispersão. O projeto de pesquisa foi aprovado pelo Comitê de Ética e Pesquisa, sob o protocolo nº006/10.Resultados: 59% das mulheres alegaram ter sofrido algum tipo de violência de gênero, na qual a psicológicaprevaleceu, representando 42,8% dos casos, seguida pela violência sexual com 27,3%, patrimonial com 25,8% efísica com 19%. Conclusão: a violência de gênero ocorre com frequência no cotidiano de usuárias dos serviçosde saúde e tem um enfrentamento deficiente. Faz-se necessário que os serviços sejam mais efetivos naprevenção, detecção e apoio às vítimas de violência.

G-CSF activation of AKT is not sufficient to prolong neutrophil survival.

Neutrophils play an important role in the innate immune response against bacterial and fungal infections. They have a short lifespan in circulation, and their survival can be modulated by several cytokines, including G-CSF. Previous studies have implicated AKT as a critical signaling intermediary in the regulation of neutrophil survival. Our results demonstrate that G-CSF activation of AKT is not sufficient to prolong neutrophil survival. Neutrophils treated with G-CSF undergo apoptosis, even in the presence of high levels of p-AKT. In addition, inhibitors of AKT and downstream targets failed to alter neutrophil survival. In contrast, neutrophil precursors appear to be dependent on AKT signaling pathways for survival, whereas high levels of p-AKT inhibit proliferation. Our data suggest that the AKT/mTOR pathway, although important in G-CSF-driven myeloid differentiation, proliferation, and survival of early hematopoietic progenitors, is less essential in G-CSF suppression of neutrophil apoptosis. Whereas basal AKT levels may be required for the brief life of neutrophils, further p-AKT expression is not able to extend the neutrophil lifespan in the presence of G-CSF.

Repercussões psicoemocionais da violência doméstica: perfil de mulheres na atenção básica / Psycho-emotional repercussions of domestic violence: the profile of women on basic healthcare

Objetivou-se com esta pesquisa investigar o perfil sociodemográfico e as repercussões psicoemocionais da violência no âmbito doméstico de mulheres atendidas em um serviço de saúde. Pesquisa de caráter exploratório-descritivo com abordagem quantitativa, desenvolvida na Unidade de Saúde da Família Cidade Verde Integrada, João Pessoa-PB. Foram entrevistadas 400 mulheres em janeiro e fevereiro de 2010, através de entrevista semiestruturada. Dessas, 211 mulheres (52,75%) foram identificadas com história de violência doméstica que compuseram a amostra do estudo. Como perfil das vítimas de violência, tivemos prevalência da faixa etária adulta (78,67%), casadas (45,04%), com renda de até dois salários (72,03%), ensino médio completo (33,17%), cor morena/parda (46,44%), religião católica (50,13%) e 56,87% não trabalhavam. As principais repercussões psicoemocionais foram tristeza, raiva e depressão. Os serviços de saúde devem servir como locais de alerta na detecção de eventos violentos, promovendo ações que facilitem a identificação do problema e seu enfrentamento.

Vigilância do crescimento infantil: conhecimento e práticas de enfermeiros da atenção primária à saúde / Surveillance to infant growth: knowledge and practice of nurses’ primary health care

Este estudo objetivou verificar os conhecimentos e práticas de enfermeiros da Estratégia Saúde da Família quanto à vigilância do crescimento de lactentes nas consultas de puericultura e informações maternas. Pesquisa quantitativa transversal realizada entre maio e junho de 2009, mediante questionário com enfermeiros e entrevista com mães em João Pessoa, Paraíba, Brasil. Para análise utilizou-se o software EPI INFO e o programa SPSS. Os enfermeiros realizaram a consulta direcionada ao crescimento e desenvolvimento infantil, porém, apenas 37,8% tinham conhecimento geral sobre o crescimento infantil, 64,4% erraram questão sobre linhas da curva do crescimento na caderneta da criança, também se observou contradição entre as informações fornecidas pelas mães e enfermeiros quanto à orientação para o desenvolvimento infantil. Diante disso, identificou-se a necessidade de atualização dos enfermeiros sobre conteúdos relacionados à saúde da criança, para realizarem a vigilância do crescimento infantil de forma integral.

Prognostic significance of leukopenia at the time of diagnosis in acute myeloid leukemia.

We investigated the clinical significance of leukopenia at the time of diagnosis in a cohort of 225 patients with newly diagnosed acute myeloid leukemia (AML) at a single institution. Leukocyte count was treated as a continuous variable and, using a receiver operating characteristic curve (ROC), a cutoff of 3,600/µL had the best sensitivity and specificity for remission (complete remission [CR]), relapse-free survival [RFS], and overall survival [OS]). In a multivariable model, leukopenia at diagnosis had no effects on CR (hazard ratio [HR] = 2.02; confidence interval [CI], 0.9-4.3; P = .07), RFS (HR = 0.93; CI, 0.5-1.5; P = .8), or OS (HR = 1.05; CI, 0.7-1.5; P = .7). No differential expression of cell surface molecules (CD34, c-Kit, CXCR4, PECAM, VLA2, VLA-, VLA4, VLA5, and FLT3) was observed on simultaneously obtained marrow and blood blasts in the high- vs. low-leukocyte groups. We conclude that leukopenia at diagnosis carries no prognostic significance in AML.

PKR activation by a non-coding RNA expressed in lymphocytes of mice bearing B16 melanoma.

In recent years, non-coding RNAs (ncRNAs) have become an exciting area of research. It has been demonstrated that ncRNAs play an important role in the regulation of gene expression in eukaryotic cells. However, little is known about ncRNAs in lymphocytes. In this study, we investigated the presence of ncRNAs in lymphocytes of C57BL/6 mice bearing B16 melanoma by using the differential display reverse transcription-PCR (DD-RT-PCR). PKR is a serine/threonine kinase containing two RNA-binding domains within the N-terminal region. We took advantage of the ability of RNAs to bind PKR in order to identify ncRNAs of lymphocytes activated during tumor development. Thus, RNAs that co-immunoprecipitated with PKR were reversed transcribed, re-amplified, cloned, sequenced and the secondary structure was determined. The ability of transcripts obtained by in vitro transcription to activate PKR was also examined. We detected a highly structured transcript of 220 nt with no open reading frame (ORF) which is able to activate PKR, and it is only expressed in lymphocytes of C57BL/6 mice bearing B16 melanoma. Therefore, the 220 nt transcript may be included in the class of ncRNAs that act by modifying protein activity and our data suggest that regulation of gene expression in activated lymphocytes by this ncRNA could be mediated by PKR through the activation of the transcription factor NF-kappaB.

Activation of the RNA-dependent protein kinase (PKR) of lymphocytes by regulatory RNAs: implications for immunomodulation in HIV infection.

It has been known for decades that exogenous RNAs are able to induce cytotoxic T lymphocytes (CTLs) and immunological reactivity to a wide variety of antigens. The molecular events responsible for these effects remain unclear for more than two decades. It has been decided to revisit this phenomenon in the light of new concepts that are just emerging in Molecular Biology, such as the regulation of gene expression by noncoding RNAs, named regulatory RNAs. The immunological effects observed in lymphocytes treated with RNAs obtained from lymph nodes of immunized animals with different types of antigens including synthetic peptides of the human immunodeficiency virus type 1 (HIV-1) have been investigated. Our recent results showed that regulatory RNAs are involved in this phenomenon, which is due to the activation of the RNA-dependent protein kinase (PKR) by regulatory RNAs with subsequent activation of the transcription factor NF-kappaB. The RNA-dependent protein kinase (PKR) is a serine/threonine kinase and contains two RNA-binding domains (RBD-I and RBD-II) within the N-terminal region. PKR is activated by viral double-stranded RNA (dsRNA) and highly structured single-stranded RNAs. This review will focus on the structure and functions of PKR including its role in HIV-1 infection. Special emphasis will be placed on a regulatory RNA, named p9-RNA, isolated from lymphocytes of animals immunized with the synthetic peptide p9 (pol: 476-484) of HIV-1. It was found that the regulatory p9-RNA induces CTLs and production of IFN-gamma. These findings showed for the first time that transcriptional control of gene expression by a regulatory RNA can be mediated by PKR through the activation of the transcription factor NF-kappaB. A model for the mechanism of action of the regulatory p9-RNA responsible for the production of IFN-gamma is proposed. Elucidating the molecular mechanism of p9-RNA may contribute to determining the rationale for the use of this regulatory RNA as an immunomodulator in HIV-infected patients.

A point mutation in the RNA-binding domain I results in decrease of PKR activation in acute lymphoblastic leukemia.

RNA-dependent protein kinase (PKR) mediates the antiviral activity of interferon and also has implications in cell growth, differentiation, and apoptosis. On the other hand, the tumor suppressor function of PKR is still controversial. PKR is a serine/threonine kinase that contains two RNA-binding domains (RBD-I and RBD-II) and RBD-I is critical for its activation. Site-directed mutagenesis studies indicated that a single amino acid substitution in RBD-I is sufficient to abolish the interaction of human PKR with RNA. Also, PKR mutants that are unable to bind RNA are inactive in vitro and have no antiproliferative activity in vivo. There have been no reports of mutations in the RNA-binding domains of PKR of tumor cells taken directly from patients. We investigated the presence of mutations in the RBD-I and RBD-II of PKR gene in children with acute lymphoblastic leukemia (ALL). The RNA extracted from bone marrow samples of 15 patients with ALL (5 patients T-lineage; 10 patients B-lineage) was used for to synthesize cDNA and amplify the sequences corresponding to RBD-I and RBD-II. The PCR products were subsequently cloned and sequenced. A point mutation was detected in the RBD-I of PKR from a patient with ALL of T-cell lineage that is located at cDNA nt 50 A --> G (17 Tyr-->Cys). We also found that activation of a PKR mutant by the polyinosinic acid:polycytidylic acid (poly I:C) is impaired when compared with the wild-type PKR. Additional work is required to elucidate whether this point mutation plays a role in the formation and/or maintenance of leukemic cells. To our knowledge, this study is the first example of detection of a mutation in the RBD-I of PKR gene from tumor cells taken directly from patients.

Regulatory RNA induces the production of IFN-gamma, but not IL-4 in human lymphocytes: role of RNA-dependent protein kinase (PKR) and NF-kappaB.

Previous results with p9-RNA, obtained from lymph nodes of animals immunized with the peptide p9 of HIV-1, suggested that its effects on lymphocytes could be mediated by RNA-dependent protein kinase (PKR). Here we report that p9-RNA activates PKR leading to the degradation of the inhibitor I-kappaB alpha and the concomitant nuclear factor kappa B (NF-kappaB) activation. The fractionation of p9-RNA by affinity chromatography indicates that the poly A(+) p9-RNA is the fraction responsible for PKR activation. We also found that p9-RNA induces the production of interferon-gamma (IFN-gamma), but not interleukin (IL-4) since only IFN-gamma gene promoter contains NF-kappaB binding site. This study provides the first evidence that transcriptional control of gene expression by regulatory RNAs can be mediated by PKR through NF-kappaB activation. A model for the mechanism of action of poly A(+) p9-RNA is proposed.

Antitumor activity induced by regulatory RNA: possible role of RNA-dependent protein kinase and nuclear factor-kappaB.

Regulatory RNAs are noncoding RNAs that can regulate gene expression. Our previous results showed that regulatory RNAs can induce the production of interleukin-1, interleukin-2, interleukin-8, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and Fas ligand (FasL). These cytokines and FasL are involved in host defense mechanisms against tumors. B16-F10 melanoma cells are highly metastatic to the lungs and we showed that lymphocytes treated with the regulatory B16-RNA reduce significantly the number of metastatic nodules. We also found that B16-RNA activates RNA-dependent protein kinase (PKR) and the active B16-RNA fraction is polyadenylated with a sedimentation coefficient of 18S. Our findings suggest that the antitumor activity of B16-RNA is mediated by PKR through activation of the transcription factor NF-kappaB. Thus, B16-RNA may act as a regulatory RNA and may regulate gene expression at transcriptional level. This study provides the rationale for the use of B16-RNA as an immunomodulator in melanoma.

Evidence for the involvement of the RNA-dependent protein kinase (PKR) in the induction of human cytotoxic T lymphocytes against a synthetic peptide of HIV-1 by regulatory RNA.

Exogenous RNA molecules can be incorporated into eukaryotic cells and can exert a variety of biological effects. We have previously showed that exogenous RNAs obtained from lymphoid organs of animals immunized with synthetic peptides of HIV-1 are able to induce cell-mediated immune responses. In this study, animals were immunized with a synthetic peptide (pol: 476-484) of HIV-1, referred to as p9, which is a cytotoxic T lymphocyte (CTL) epitope. The RNA extracted from the lymphoid organs of animals immunized with p9 was termed p9-RNA. We have demonstrated that p9-RNA is active in inducing human CTL. The p9-RNA was also able to activate the RNA-dependent protein kinase (PKR) of human lymphocytes. The polyA(+) p9-RNA was the fraction responsible for the activation of this protein kinase. We also found that p9-RNA activates the transcription factor nuclear kappa B (NF-kappaB) by inducing the degradation of its inhibitor I-kappaB. Thus, these findings suggest that p9-RNA may act as a regulatory RNA and that the induction of CTL activity by p9-RNA could be mediated by PKR through NF-kappaB activation. It is known that CTL activity plays an important role in host defense against HIV-1 infection. Elucidating the molecular mechanism of p9-RNA could contribute to determining the basis for the use of p9-RNA as an immunomodulator in HIV-infected patients.

Activation of RNA-dependent protein kinase and nuclear factor-kB by regulatory RNA from lipopolysaccharide-stimulated macrophages: implications for cytokine production.

Our previous results showed that L-RNA, extracted from lipopolysaccharide-stimulated macrophages, induces interleukin-1, interleukin-8 and tumor necrosis factor-alpha (TNF-alpha) in resident macrophages. It was demonstrated the promoter of these cytokine genes contain nuclear factor-kB (NF-kappa B) binding sites. We hypothesized that this effect of L-RNA is mediated by RNA-dependent protein kinase (PKR) through NF-kappa B activation. We found that L-RNA activates PKR and induces NF-kappa B activation through degradation of its inhibitor I-kappa B alpha. These data support the idea that L-RNA acts as a regulatory RNA. A model for the mechanism of action of L-RNA is proposed.