Combination Therapy as a Promising Way to Fight Oral Cancer.

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.

Comparison Between Surgical and Conservative Treatment for AOSpine Type A3 and A4 Thoracolumbar Fractures without Neurological Deficit: Prospective Observational Cohort Study / Comparação entre tratamento cirúrgico e conservador para fraturas toracolombares AOSpine tipo A3 e A4 sem déficit neurológico: Estudo de coorte prospectivo observacional

Abstract Objective To compare the clinical results between conservative (CS) and surgical treatment (CXS) of A3 and A4 fractures without neurological deficit. Methods Prospective observational study of patients with thoracolumbar fractures type A3 and A4. These patients were separated between the surgical and conservative groups, and evaluated sequentially through the numeric rating scale (NRS), Roland-Morris disability questionnaire (RMDQ), EuroQol-5D (EQ-5D) quality of life questionnaire, and Denis work scale (DWS) up to 2.5 years of follow-up. Results Both groups showed significant improvement, with no statistical difference in pain questionnaires (NRS: CXS 2.4 ± 2.6; CS 3.5 ± 2.6; p> 0.05), functionality (RMDQ: CS 7 ± 6.4; CXS 5.5 ± 5.2; p> 0.05), quality of life (EQ-5D), and return to work (DWS). Conclusion Both treatments are viable options with equivalent clinical results. There is a tendency toward better results in the surgical treatment of A4 fractures.

Resumo Objetivo Comparar os resultados clínicos entre os tratamentos conservador (CS) e cirúrgico (CXS) das fraturas A3 e A4 sem déficit neurológico. Métodos Estudo prospectivo observacional de paciente com fraturas toracolombares tipo A3 e A4. Esses pacientes foram separados entre os grupos cirúrgico e conservador e avaliados sequencialmente através da escala numérica de dor (NRS), do questionário de incapacidade de Roland-Morris (RMDQ), do EuroQol-5D (EQ-5D) e da escala de trabalho de Denis (DWS) até 2,5 anos de acompanhamento. Resultados Ambos os grupos apresentaram melhora significante, sem diferença estatística nos questionários de dor (NRS: CXS 2,4 ± 2,6; CS 3,5 ± 2,6; p> 0,05), funcionalidade (RMDQ: CS 7 ± 6,4; CXS 5,5 ± 5,2; p> 0,05), qualidade de vida (EQ-5D) e retorno ao trabalho (DWS). Conclusão Ambos os tratamentos são opções viáveis e com resultados clínicos equivalentes. Há uma tendência a melhores resultados no tratamento cirúrgico das fraturas A4.

Epidemiological patterns of adolescent idiopathic scoliosis in a spinal center in curitiba / Epidemiologia da escoliose idiopática do adolescente de um centro especializado em curitiba / Epidemiología de la escoliosis idiopática en adolescentes en un centro especializado en curitiba

ABSTRACT: Objective: Evaluation of the profile of the population with adolescent idiopathic scoliosis (AIS) treated at a center specializing in spine surgery in Curitiba-PR. Methods: Prospective multicenter study, being analyzed, at the moment, only data from the center in question. All patients referred from the basic health service for evaluation of deformity underwent panoramic radiography of the total spine to evaluate the curvature using the Cobb method, evaluation of skeletal maturity using the Risser classification, and the classification of scoliosis using the Lenke classification. Clinical photographs of all patients and an assessment of the quality of life using the SRS-30 questionnaire were also taken. Results: Thirty patients with scoliosis and a mean age of 14.63 ± 3 years were evaluated. Prevalence of female:male 1.5:1. Patients had a mean Cobb of 45.96°, and most were close to Risser 4 skeletal maturity (48.3%). 60% had a thoracic curve (Lenke 1), and 13.3% had a double curve (Lenke 3 or 6). 63.3% of cases had a delay in medical care, taking an average of 18 months between referral and consultation with a specialist. 60% of patients were referred for surgical treatment after the first appointment. Conclusion: The population sample of this center follows the literature. A Cobb >40° in the first consultation with a specialist and a high referral rate to surgery suggest the failure of early diagnosis and the need for public policies for better knowledge and assistance for adolescent idiopathic scoliosis. Level of Evidence IV; Descriptive Epidemiological Study.

RESUMO: Objetivo: Avaliação do perfil da população com escoliose idiopática do adolescente (EIA) atendida no centro especializado em cirurgia de coluna em Curitiba-PR. Métodos: Estudo multicêntrico prospectivo, sendo analisados, no momento, somente os dados do centro em questão. Todos os pacientes encaminhados do serviço de saúde básica para avaliação de deformidade foram submetidos a radiografia panorâmica de coluna total para avaliação da curvatura através do método de Cobb, avaliação da maturidade esquelética pela classificação de Risser e classificação da escoliose por Lenke. Foram, também, realizadas fotos clínicas de todos os pacientes e avaliação da qualidade de vida pelo questionário SRS-30. Resultados: Foram avaliados 30 pacientes com escoliose e idade média de 14,63 ± 3 anos. Prevalência de sexo feminino:masculino 1,5:1. Os pacientes apresentavam Cobb médio 45,96° e a maioria estava próxima da maturidade esquelética Risser 4 (48,3%). 60% apresentavam curva torácica (Lenke 1) e 13,3% dupla curva (Lenke 3 ou 6). 63,3% dos casos apresentaram atraso na assistência médica, demorando em média 18 meses entre o encaminhamento e a consulta com especialista. 60% dos pacientes foram encaminhados para tratamento cirúrgico após a primeira consulta com um especialista. Conclusão: A amostra populacional deste centro encontra-se consoante a literatura. Pelo Cobb >40° na primeira consulta com o especialista e a alta taxa de encaminhamento para cirurgia, fica demonstrado a falha do diagnóstico precoce e necessidade de políticas públicas para melhor conhecimento e assistência da escoliose idiopática do adolescente. Nível de evidência: IV; Estudo Epidemiológico Descritivo.

RESUMEN: Objetivo: Evaluación del perfil de la población con escoliosis idiopática del adolescente (EIA) tratada en un centro especializado en Curitiba-PR. Métodos: Estudio multicéntrico prospectivo, analizándose, por el momento, únicamente los datos del centro en cuestión. A todos los pacientes derivados del servicio básico de salud para evaluación de deformidad se les realizó radiografía panorámica de columna total para evaluación de la curvatura mediante el método de Cobb, evaluación de la madurez esquelética mediante la clasificación de Risser y clasificación de escoliosis mediante la clasificación de Lenke. También se tomaron fotografías clínicas de todos los pacientes y evaluación de la calidad de vida mediante el cuestionario SRS-30. Resultados: Se evaluaron 30 pacientes con escoliosis y edad media de 14,63 ± 3 años. Prevalencia femenino:masculino 1,5:1. Los pacientes tenían un Cobb medio de 45,96° y la mayoría estaba cerca de la madurez esquelética Risser 4 (48,3%). El 60% tenía curva torácica (Lenke 1) y el 13,3% tenía doble curva (Lenke 3 o 6). El 63,3% de los casos tuvo retraso en la atención médica, transcurriendo en promedio 18 meses entre la derivación y la consulta con un especialista. El 60% de los pacientes fueron derivados para tratamiento quirúrgico después de la primera cita. Conclusión: La muestra poblacional de este centro está de acuerdo con la literatura. Por Cobb > 40° en la primera consulta con un especialista y una alta tasa de derivación a cirugía, se sugiere el fracaso del diagnóstico precoz y la necesidad de políticas públicas para mejorar el conocimiento y la asistencia de la escoliosis idiopática del adolescente. Nivel de Evidencia IV; Estudio Epidemiológico Descriptivo.

Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction.

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness.

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems.

The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.

LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model.

Cationic anticancer peptides have exhibited potent anti-proliferative and anti-inflammatory effects in neoplastic illness conditions. LyeTx I-b is a synthetic peptide derived from Lycosa erythrognatha spider venom that previously showed antibiotic activity in vitro and in vivo. This study focused on the effects of LyeTxI-b on a 4T1 mouse mammary carcinoma model. Mice with a palpable tumor in the left flank were subcutaneously or intratumorally injected with LyeTx I-b (5 mg/kg), which significantly decreased the tumor volume and metastatic nodules. Histological analyses showed a large necrotic area in treated primary tumors compared to the control. LyeTxI-b reduced tumor growth and lung metastasis in the 4T1 mouse mammary carcinoma model with no signs of toxicity in healthy or cancerous mice. The mechanism of action of LyeTx I-b on the 4T1 mouse mammary carcinoma model was evaluated in vitro and is associated with induction of apoptosis and cell proliferation inhibition. Furthermore, LyeTx I-b seems to be an efficient regulator of the 4T1 tumor microenvironment by modulating several cytokines, such as TGF-ß, TNF-α, IL-1ß, IL-6, and IL-10, in primary tumor and lung, spleen, and brain. LyeTx I-b also plays a role in leukocytes rolling and adhesion into spinal cord microcirculation and in the number of circulating leukocytes. These data suggest a potent antineoplastic efficacy ofLyeTx I-b.

Carcinoma ductal in situ associado à fibroadenoma: relato de caso / Carcinoma ductal in situ arising in a fibroadenoma: report of a rare case

Apesar de fibroadenoma ser uma das lesões mais comuns da mama, sua correlação a alteração maligna é rara.1,2,3,5,7 Quando ocorre tem apresentação clínica similar a dos fibroadenomas típicos, diagnóstico anatomopatológico em geral pós-cirúrgico e tratamento conforme do carcinoma do mesmo tipo histológico isolado.1,2,3,4,6 Apresentamos caso de mulher de 52 anos, apresentando em propedêutica investigativa nódulo em mama direita. Core-biopsy sugeriu carcinoma ductal in situ desenvolvido dentro de fibroadenoma, confirmado em análise anatomopatológica pósoperatória. Tratamento e seguimento se deu conforme já estabelecido pela literatura para carcinoma in situ. Devido baixa incidência, há poucas evidências científicas quanto ao diagnóstico, tratamento e prognóstico desse tipo de lesão. Portanto, apresentar à comunidade científica casos de carcinoma inclusos a fibroadenoma se faz relevante.

Although fibroadenoma is one of the most common lesions of the breast, its correlation with malignant changes is rare. When it occurs, the clinical presentation is similar to typical fibroadenomas, anatomopathological diagnosis is after surgery and treatment goes according to the carcinoma histological type. A case of a 52-year-old woman is presented, with an impalpable nodule in the right breast, diagnosed from screening exams. Corebiopsy suggested carcinoma ductal in situ developed within fibroadenoma, confirmed in the postoperative anatomopathological analysis. Treatment and follow-up followed as established in the literature for carcinoma in situ. Due the low incidence, there are poor scientific evidence regarding the diagnosis, treatment and prognosis of this type of injury. Therefore, presenting cases of Carcinoma ductal in situ arising in a fibroadenoma to the scientific community is so relevant.

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research.

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell-cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

Assessing the cytotoxic/genotoxic activity and estrogenic/antiestrogenic potential of essential oils from seven aromatic plants.

Alternative therapies with new drugs are needed because the clinical efficacy of conventional chemotherapy is often reduced due to collateral effects. Many natural products of plant origin, including essential oils (EOs) have proved to be effective in prevention and therapy of several diseases such as bacterial infections, chronic diseases and cancer. In the present study, we investigated some biological activities of EOs extracted from seven plants: Rosmarinus officinalis, Salvia somalensis, Thymus vulgaris, Achillea millefolium, Helichrysum italicum, Pistacia lentiscus, Myrtus communis. In particular, we evaluated the cytotoxic and genotoxic activity using the cytochalasin B-blocked micronucleus assay (CBMN) in human peripheral lymphocytes, cytotoxicity in a human ovarian carcinoma cell line (A2780), and the estrogenic/antiestrogenic activity using a yeast strain expressing the human estrogen receptor alpha (ERα). Our results show that most EOs can have a strong cytotoxic and a slight/moderate genotoxic effect on human peripheral lymphocytes, and also a pronounced cytotoxic effect in A2780 cells. In addition, some EOs seem to have a marked antiestrogenic activity that could potentially perturb the estrogen-dependent tissues.

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice.

BACKGROUND: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. METHODS: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. RESULTS: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. CONCLUSIONS: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity.

Efeitos sistêmicos da mobilização precoce em pacientes adultos internados na unidade de terapia intensiva: revisão atualizada / Systemic effects of early mobilization in adult patients admitted to the intensive care unit: updated review

Introdução: Nos últimos anos, com o avanço tecnológico e da medicina, a sobrevida dos pacientes internados nas unidades de terapia intensiva (UTI) tem aumentado consideravelmente. No entanto, muitos desses pacientes permanecem imóveis e restritos ao leito causando diversas consequências deletérias associadas à imobilidade prolongada. Objetivo: Elucidar os efeitos sistêmicos da mobilização precoce em pacientes adultos internados na UTI. Métodos: Trata-se de uma revisão realizada nas bases de dados eletrônica: Pubmed, Scielo e Web of Science. Foram selecionados artigos indexados publicados entre o período de 2012 a 2017. Foram encontrados 9 estudos relevantes a essa revisão. Resultados: De forma geral, essa prática proporcionou aumento da força muscular, aumento da pressão inspiratória máxima, redução na produção de citocinas pró-inflamatórias e do estresse oxidativo, menor permanência na ventilação mecânica (VM), menor tempo de internação hospitalar e maior qualidade de vida. Conclusão: A fisioterapia torna-se essencial no desenvolvimento da mobilização precoce, contribuindo para a melhora da funcionalidade e da qualidade de vida do paciente tanto no meio hospitalar quanto pós-alta.

Introduction: In recent years, with advances in technology and medicine, the survival of patients admitted to intensive care units (ICU) has increased considerably. However, many of these patients remain immobile and restricted in the beds causing several deleterious consequences associated with prolonged immobility. Objective: To elucidate the systemic effects of early mobilization in adult patients hospitalized in the ICU. Methods: This is a review carried out in the electronic databases: PubMed, Scielo and Web of Science. We selected indexed articles between 2012 and 2017. We found 9 studies relevant to this review. Results: In general, this practice increased muscle strength, increased maximal inspiratory pressure, reduced production of proinflammatory cytokines and oxidative stress, shorter mechanical ventilation (MV), shorter hospital stay and higher quality of life. Conclusion: Physical therapy becomes essential in the development of early mobilization, contributing to improve the functionality and quality of life of the patient both in hospital and post-discharge.

Thalidomide in plasma cell balanitis refractory to conventional topical treatment

Abstract: Zoon's plasma cell balanitis is a chronic genital inflammatory dermatosis that affects uncircumcised men, especially the elderly. It's characterized by painless erythematous plaques of orange hue, located on the glans penis and foreskin. Circumcision is the most effective treatment; however, it can be hard for patients to accept. As an alternative, topical calcineurin inhibitors are used, with good response. This article reports the case of a 32-year-old patient, HIV carrier, diagnosed with Zoon's plasma cell balanitis. Treatment with topical tacrolimus was administered, without improvement. A 6-week course of thalidomide resulted in complete remission of the lesions, without recurrence after eight months of follow-up.

Assistance provided by physical therapists from primary health care to patients after stroke / Assistência do fisioterapeuta da atenção primária a indivíduos pós-acidente vascular cerebral

Abstract Introduction: Motor impairments, which are prevalent in stroke subjects, require physical therapy (PT) rehabilitation. In primary care in the Brazilian Public Health System, PT are part of the Núcleo de Apoio à Saúde da Família (NASF). Objective: To describe the PT assistance provided to stroke patients in a primary healthcare center. Methods: The records of all stroke patients (n = 44; 69.23 ± 13.12 years) identified by the health professionals were analyzed. Using keyword recognition, frequency analysis of the services offered by the PT was performed. Subjects were classified according to the Modified Rankin Scale. Results: In the 44 records, 45.5% had a description of the assistance provided by any professional of the NASF and 36.4% of the PT care. PT care was provided at the subject's home (94.2%) and at the healthcare center (5.8%). The PT practices were identified as: orientation (93.8%), evaluation (87.5%), exercises (50%), follow-up (37.5%), referral to another service or to undergrad PT students (18.8%), and referral to other NASF professionals (12.5%). Most of the subjects were classified as having mild/moderate disability. Conclusion: The minority of records had registration of attendance by the NASF PT. The majority of the sessions occurred at the subject's home, which reveals a practice focused on individual care. The orientation was common, which illustrates that in primary care there is a focus on empowerment for health self-improvement. Follow-up was not common, despite clinical guidelines state that stroke subjects should be monitored at least once a year by the rehabilitation team.

Resumo Introdução: Deficiências motoras são prevalentes após o Acidente Vascular Cerebral (AVC), necessitando de atendimento fisioterápico (AF). Na atenção básica (AB) do Sistema Único de Saúde, os fisioterapeutas fazem parte do Núcleo de Apoio à Saúde da Família (NASF). Objetivo: Descrever o perfil da RF do NASF aos indivíduos pós-AVC usuários da AB. Métodos: Os prontuários de todos indivíduos pós-AVC (n=44) foram analisados. Com o reconhecimento de palavras-chave, realizou-se análise de frequência das condutas do AF. Em seguida, os indivíduos foram avaliados quanto à auto-percepção de saúde e incapacidade (Escala Modificada de Rankin). Resultados: A maioria avaliou sua saúde como razoável ou ruim (61%) e 31,8% apresentaram incapacidade severa. Apesar disso, apenas 45,5% dos prontuários apresentava registro de assistência do NASF, sendo o AF o mais frequente: 36,4% receberam AF, com um total de 35 atendimentos. Desses, 94,2% foram em domicílio, contemplando as seguintes condutas: orientação (93,8% dos casos), avaliação (87,5%), tratamento (50%), acompanhamento (37,5%), encaminhamento a outro serviço ou para acadêmicos da fisioterapia (18,8%) e encaminhamento a outro profissional do NASF (12,5%). Conclusão: Apesar de ser o profissional do NASF com atendimento mais frequente, a minoria dos prontuários apresentava registro de AF. Os atendimentos ocorreram, principalmente, em domicílio, revelando que a prática profissional pauta-se em atendimentos individualizados. A grande quantidade de orientação ilustra que a fisioterapia na AB contempla o empoderamento como cuidado à saúde. O acompanhamento foi uma prática pouco frequente, apesar de estabelecido em guias clínicos que indivíduos pós-AVC devem ser acompanhados pelo menos anualmente pela equipe de reabilitação.

Increased level of DNA damage in some organs of obese Zucker rats by γ-H2AX analysis.

In a recent study, we showed that lymphocytes of obese Italian children/adolescents displayed levels of double strand breaks (DSB), assayed as serine 139-phosphorylated histone H2AX (γ-H2AX), about eightfold higher than normal weight controls, and that 30% of this damage-generated micronuclei. These findings suggested that obese children could be at increased risk of obesity-mediated cancer later in life. We therefore aimed to assess the level of γ-H2AX in a genetic animal model of obesity (Zucker rat) to identify a genotoxic/carcinogenic risk in some organs. The DSB marker was studied in 3- to 4-week-old rats and in 9- to 13-week-old rats. Paraffin-embedded sections of heart, thyroid, liver, pancreas, lung, kidney, esophagus, and gut from the fa-/fa- (obese) and the fa+/fa- (lean) control animals were processed for immunohistochemistry detection of γ-H2AX. Pancreas (0.0624 ± 0.0195), lung (0.1197 ± 0.0217), esophagus (0.1230 ± 0.0351), kidney (0.1546 ± 0.0149), and gut (0.1724 ± 0.0352) of 9- to 13-week-old obese rats showed a higher proportion of γ-H2AX-positive nuclei, than their lean counterparts (0.0092 ± 0.0033, 0.0416 ± 0.0185, 0.0368 ± 0.0088, 0.0686 ± 0.0318, and 0.0703 ± 0.0239, respectively). No difference was seen in the 3- to 4-week-old age group with regard to obesity, indicating that the DNA damage increased with older age of the rats. We hypothesize that the organs of the obese animals showing high levels of DSB could represent target tissues for the development of obesity-related cancers. Environ. Mol. Mutagen. 58:477-484, 2017. © 2017 Wiley Periodicals, Inc.

Atuação da fisioterapia no esforço respiratório em crianças hospitalizadas com infecção respiratória aguda: um estudo comparativo / Physical therapy performance in respiratory effort in hospitalized children with acute respiratory infection: a comparative study

Introdução: As infecções respiratórias agudas (IRA) são as causas mais comuns de morbimortalidade na infância. O Boletim de Silverman-Andersen (BSA) é um instrumento utilizado na prática clínica pediátrica para avaliar cinco aspectos do desconforto respiratório e quantificá-los. Objetivo: Comparar a efetividade do tratamento fisioterapêutico com 1 ou 2 sessões diárias durante 2 dias consecutivos, em crianças entre 0 e 3 anos hospitalizadas com IRA, utilizando o BSA. Métodos: Trata-se de um estudo clínico cego realizado com 23 crianças que foram separadas em dois grupos aleatoriamente: o G1, composto por crianças que apenas foram submetidas ao tratamento oferecido pelo hospital e o G2 que, além dessa mesma intervenção, foram submetidas a um segundo atendimento padronizado. Os resultados foram analisados através do programa Prisma versão 5.0. Resultados: Nas análises dos dados da reavaliação de ambos os grupos, foi evidenciada diferença estatisticamente significativa nos escores do Boletim de Silverman Andersen (p = 0,0114). Conclusão: Observou-se que houve melhora do esforço respiratório e das condições clínicas em curto prazo das crianças submetidas a dois atendimentos fisioterapêuticos diários. (AU)

Introduction: Acute respiratory infections (ARI) are the most common causes of morbidity and mortality in childhood. The Bulletin Silverman-Andersen (BSA) is an instrument used in pediatric clinical practice to evaluate five aspects of respiratory distress and quantifies them. Objective: To compare the effectiveness of physical therapy with 1 or 2 sessions daily for 2 consecutive days, in children aged 0 to 3 years hospitalized with ARI using the BSA. Methods: This is a clinical blind randomized study of 23 children who were separated into two groups: the G1, composed of children who were only subjected to the treatment provided by the hospital and the G2 that, beyond such intervention were submitted a second standard care. The results were analyzed using the Prism software, version 5.0. Results: In the analysis of the re-evaluation of data from both groups was evidenced statistically significant difference in Silverman Andersen Bulletin scores (p = 0.0114). Conclusion: It was demonstrating improved respiratory effort and clinical conditions in the short term of children undergoing two daily physical therapy sessions.(AU)

Impacto da cárie dentária, maloclusão e hábitos orais na qualidade de vida relacionada à saúde oral em crianças pré-escolares / Impact of dental caries, malocclusion and oral habits on the oral health-related quality of life of preschool children

RESUMO Introdução As doenças e desordens bucais, bem como hábitos orais, podem causar impacto na qualidade de vida das crianças. Objetivo Associar a cárie dentária, maloclusão e hábitos orais com a qualidade de vida de crianças pré-escolares. Métodos Estudo transversal com 93 crianças de 3 a 5 anos de idade, acometidas, ou não, por lesões de cárie não tratadas. Os responsáveis responderam ao questionário sobre hábitos orais e ao Questionário sobre a Qualidade de Vida Relacionada à Saúde Bucal de Crianças na Idade Pré-escolar (B-ECOHIS). Um odontopediatra avaliou a gravidade das lesões de cárie e a presença de alterações oclusais. O nível de significância utilizado foi de 5%. Resultados O B-ECOHIS evidenciou impacto na qualidade de vida, conforme o aumento da idade, nos domínios dos sintomas, aspectos psicológicos, autoimagem e interação social e de função familiar. A cárie dentária apresentou impacto sobre a qualidade de vida das crianças e de seus familiares, especialmente em relação aos domínios dos sintomas e limitações. Hábitos de respiração oronasal e chupeta também evidenciaram efeitos negativos na qualidade de vida das crianças e de seus familiares. Não foi observada associação entre maloclusão e qualidade de vida relacionada à saúde oral. Conclusão A cárie dentária, os hábitos de sução de chupeta e de respiração oronasal demonstraram impacto negativo na qualidade de vida relacionada à saúde oral das crianças.

ABSTRACT Introduction Oral diseases and disorders as well as oral habits can impact the quality of life of children. Purpose To associate the dental caries, malocclusion and oral habits with the quality of life of preschool children. Methods Cross-sectional study with 93 children from three to five years of age who have or have not been affected by untreated carious lesions. Parents answered the questionnaire on oral habits and quality of life instrument related to oral health denominated Early Childhood Oral Health Impact Scale (B-ECOHIS). A pediatric dentist assessed the severity of the carious lesions and the presence of occlusal disorders. The level of significance used was 5%. Results The B-ECOHIS demonstrated impact on quality of life with increasing age in the fields of symptoms, psychological aspects, self-image and social interaction and family function. Dental caries were shown to have an impact on the quality of life of children and their families, especially in relation the domains of symptoms and limitations. Oronasal breathing and pacifier habits negatively impacted the quality of life of children and their families. There was no association between malocclusion and quality of life related to oral health. Conclusion The dental caries, the pacifier suction habits and oronasal breathing demonstrated negative impact on quality of life related to oral health of children.

Cuidados com a Saúde Autosselecionados pelos Usuários da Atenção Primária / Health Initiatives Self Selected by Users of Primary Healthcare

RESUMO Este estudo descreve as mudanças em cuidados com a saúde que usuários da atenção primária escolheram adotar após participarem de uma ação de educação em saúde sobre cuidados com a saúde e determinar o grau de comprometimento desses usuários com essas mudanças autoestabelecidas. Foi desenvolvida uma ação de educação em saúde com usuários da atenção primária sobre cuidados com a saúde. Os indivíduos foram avaliados imediatamente após esta ação e dois a três meses depois, por meio de um questionário semiestruturado. Os relatos foram analisados pela análise de conteúdo. Entre os participantes, 31% tiveram como objetivo praticar atividade física, 28% melhorar a alimentação, 22,9% cuidar da saúde mental, 12,6% emagrecer, 10,3% cuidar da saúde em geral, 6,9% consumir menos álcool, 4,6% parar de fumar, e 1,15% cuidar do meio ambiente. Após dois a três meses, 8,62% não se lembraram e não cumpriram as metas autoestabelecidas, 22,41% as cumpriram totalmente, e 68,97%, apesar de se lembrarem, não as cumpriram. Desses, 77,5% apontaram como motivo para o não cumprimento a falta de disciplina, 17,5% a falta de tempo e 5% problemas de saúde.

ABSTRACT The aim of this study was to describe changes in self-care to be adopted by users of primary healthcare services in Brazil upon participation in a health education initiative, and to determine their involvement with these changes. A health education initiative was therefore developed with users of primary healthcare services in Brazil, with subjects assessed immediately afterwards and then two to three months apart (by means of a semi-structured questionnaire). Analyzed according to content analysis, reports showed that 31% of participants selected physical activity as a means of improving their health, 28% selected improving food habits, 22.9% improving mental care, 12.6% losing weight, 10.3% healthcare in general, 6.9% drinking less alcohol, 4.6% quitting smoking and 1.15% caring for the environment. After two to three months, 8.62% did not remember which they had selected to improve their health while 22.41% performed the selected initiative and 68.97% remembered their selection without going on to take the actions. Among participants, 77.5% claimed not to have been committed to the actions selected, 17.5% reported not having time and 5% said they suffered from health problems.

Health, function and disability in stroke patients in the community

ABSTRACT Background Stroke patients commonly have impairments associated with reduction in functionality. Among these impairments, the motor impairments are the most prevalent. The functional profile of these patients living in the community who are users of the primary health-care services in Brazil has not yet been established Objective To describe the functional profile of stroke patients who are users of the primary health-care services in Brazil, looking at one health-care unit in the city of Belo Horizonte, Brazil. Method From medical records and home visits, data were collected regarding health status, assistance received following the stroke, personal and environmental contextual factors, function and disability, organized according to the conceptual framework of the International Classification of Functioning, Disability and Health (ICF). Test and instruments commonly applied in the assessment of stroke patients were used. Results Demographic data from all stroke patients who were users of the health-care unit (n=44, age: 69.23±13.12 years and 67±66.52 months since the stroke) participated of this study. Most subjects presented with disabilities, as changes in emotional function, muscle strength, and mobility, risks of falling during functional activities, negative self-perception of quality of life, and perception of the environment factors were perceived as obstacles. The majority of the patients used the health-care unit to renew drug prescriptions, and did not receive any information on stroke from health professionals, even though patients believed it was important for patients to receive information and to provide clarifications. Conclusion Stroke patients who used primary health-care services in Brazil have chronic disabilities and health needs that require continuous health attention from rehabilitation professionals. All of these health needs should be considered by health professionals to provide better management as part of the integral care of stroke patients, as recommended by the clinical practice guidelines for stroke rehabilitation.

Perfil mastigatório em crianças de três a cinco anos de idade / Masticatory profile in children from three to five-years old

RESUMO: Objetivo: descrever o perfil mastigatório em crianças de três a cinco anos de idade, correlacionando-o com a idade cronológica, gênero, hábitos orais, introdução alimentar e aspectos dentários. Métodos: estudo transversal realizado com 60 crianças de ambos os gêneros. Um odontopediatra avaliou o aspecto dentário, seguida da avaliação da mastigação realizada por uma fonoaudióloga, utilizando-se pão francês e o protocolo elaborado para este estudo. A coleta de dados da mastigação foi realizada por meio de registro em vídeo e posterior análise por avaliadores cegos. Os responsáveis responderam o questionário sobre os hábitos orais e introdução alimentar. Resultados: nos 10 itens avaliados na mastigação ocorreu alternância entre o padrão esperado para todas as váriaveis. Foi observada diferença estatística entre a postura de lábios das crianças de três e quatro anos quando comparadas com as de cinco anos de idade (p<0,001). Os movimentos mandibulares predominantes do tipo rotatório evoluíram conforme o aumento da idade (p=0,008). Não foi encontrada associação entre os aspectos dentários e a mastigação das crianças. Foi verificada associação entre: a mastigação de meninas e meninos (p=0,001); a evolução mastigatória conforme a idade (p=0,008); apresentar hábitos orais para o item modo de corte (p=0,003) e ser respirador oronasal foi fator significante para a criança realizar a mastigação de boca aberta (p=0,01) e para realizar os movimentos mandibulares de maceração predominantemente (p=0,04). Conclusão: para a amostra estudada, o modo mastigatório apresentou-se gradativo em sua evolução e aperfeiçoamento. Foi encontrada diferenciação na mastigação conforme a idade, gênero, hábitos orais e modo respiratório.

ABSTRACT: Purpose: to describe the characteristics of the chewing profile in children from 3 to 5-years old, correlating it with the chronological age, gender, oral habits, feeding introduction and dental aspects of them. Methods: transversal study performed with 60 children of both genders. A pediatric dentistry dental aspects evaluated, followed by evaluation of chewing performed by a speech therapist using French bread and the elaborate protocol for this study. Data analysis was carried through visual observation and video recording and late analysis by blind raters. The responsible answered a questionnaire about the oral habits and food introduction. Results: at the 10 items evaluated chewing occurred toggle between the standard expected for all variables. A statistical difference between the posture of lips of three- and four years compared to the five years of age (p<0.001). The predominant mandibular movements of the rotary type evolved with increasing age (p=0.008). No association was found between dental aspects and mastication of children. Association was found between: girls and boys chewing characteristics (p<0.001); mastication evolution according to age (p=0,008); to present oral habits for the item cut so (p=0.003) and was mixed respiratory significant factor in the child hold his mouth open chewing (p=0.01) and to carry out the jaw movements of maceration predominantly (p=0,04). Conclusion: for the studied sample, the chewing so presented itself gradually in its evolution and improvement. Found in chewing differentiation according to age, gender, oral habits and breathing mode.

Medidas antropométricas orofaciais em crianças de três a cinco anos de idade / Anthropometrical orofacial measurement in children from three to five years old

OBJETIVO: obter as medidas antropométricas orofaciais em crianças pré-escolares de três a cinco anos e realizar a correlação com idade cronológica, gênero, raça e hábitos orais. MÉTODOS: estudo transversal com 93 crianças selecionadas por meio de amostra de conveniência consecutiva. Os responsáveis responderam a um questionário sobre os hábitos orais e as crianças foram submetidas a uma avaliação odontológica e antropométrica da face. O nível de significância utilizado foi p<0,05. RESULTADOS: as médias das medidas antropométricas orofaciais foram descritas. Houve diferença estatística nas medidas de altura da face (p<0,001), terço médio da face (p<0,001), canto externo do olho até a comissura labial esquerda/direita (p<0,001) e lábio inferior (p=0,015) nas faixas etárias. O gênero masculino apresentou medidas superiores na altura de face (p=0,003), terço inferior da face (p<0,001), lábio superior (p=0,001) e lábio inferior (p<0,001). Não houve diferença estatisticamente significante na altura do lábio superior em sujeitos não brancos (p=0,03). A presença de hábitos orais não influenciou os resultados. O aleitamento materno exclusivo por seis meses influenciou o aumento da medida de terço médio (p=0,022) e da altura da face (p=0,037). CONCLUSÃO: as médias descritas neste estudo foram superiores aos padrões encontrados em outros estudos. As médias orofaciais aumentaram conforme a idade. Houve superioridade nas medidas para o gênero masculino e para as crianças não brancas, mas não para presença de hábitos orais. .

PURPOSE: to obtain the orofacial anthropometric measurements in preschool children from three to five years old and analyze the connection of these data with chronological age, gender, race, and oral habits. METHODS: this consisted on a transversal study with 93 children selected through consecutive convenience sample. Parents answered a questionnaire about the oral habits and children underwent odontological and orofacial anthropometric evaluation. The significance level was set at <0.05. RESULTS: the averages of orofacial anthropometric measurements were described. There were statistical differences in measures of middle third of the face (p<0.001), lower face (p<0.001), face height (p<0.001) and lower lip (p=0.015) across the age groups. Males showed higher mesures in height of the face (p=0.003), lower face (p<0.001), upper lip (p=0.001) and lower lip (p<0.001) than females. There was no statistically significant difference in the height of the upper lip in non-white subjects (p=0.03). The presence of oral habits did not influence the outcomes. The exclusive breastfeeding for six months influenced the rise of the middle third (p=0.022) and height of the face (p=0.037). CONCLUSION: the measurements described in this study were higher than those found in other studies. The orofacial measurement increased with age. The measures were higher on males and non-white children, but not for the presence of oral habits. .