Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias.

We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.

Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: The approval of Bruton tyrosine kinase (BTK) inhibitors in patients with previously untreated chronic lymphocytic leukaemia (CLL) was based on trials which compared ibrutinib with alkylating agents in patients considered unfit for fludarabine, cyclophosphamide, and rituximab, the most effective chemoimmunotherapy in CLL. We aimed to assess whether ibrutinib and rituximab is superior to fludarabine, cyclophosphamide, and rituximab in terms of progression-free survival. METHODS: This study is an interim analysis of FLAIR, which is an open-label, randomised, controlled, phase 3 trial in patients with previously untreated CLL done at 101 UK National Health Service hospitals. Eligible patients were between 18 and 75 years of age with a WHO performance status of 2 or less and disease status requiring treatment according to International Workshop on CLL criteria. Patients with greater than 20% of their CLL cells having the chromosome 17p deletion were excluded. Patients were randomly assigned (1:1) by means of minimisation (Binet stage, age, sex, and centre) with a random element in a web-based system to ibrutinib and rituximab (ibrutinib administered orally at 420 mg/day for up to 6 years; rituximab administered intravenously at 375 mg/m2 on day 1 of cycle 1 and at 500 mg/m2 on day 1 of cycles 2-6 of a 28-day cycle) or fludarabine, cyclophosphamide, and rituximab (fludarabine 24 mg/m2 per day orally on day 1-5, cyclophosphamide 150 mg/m2 per day orally on days 1-5; rituximab as above for up to 6 cycles). The primary endpoint was progression-free survival, analysed by intention to treat. Safety analysis was per protocol. This study is registered with ISRCTN, ISRCTN01844152, and EudraCT, 2013-001944-76, and recruiting is complete. FINDINGS: Between Sept 19, 2014, and July 19, 2018, of 1924 patients assessed for eligibility, 771 were randomly assigned with median age 62 years (IQR 56-67), 565 (73%) were male, 206 (27%) were female and 507 (66%) had a WHO performance status of 0. 385 patients were assigned to fludarabine, cyclophosphamide, and rituximab and 386 patients to ibrutinib and rituximab. After a median follow-up of 53 months (IQR 41-61) and at prespecified interim analysis, median progression-free survival was not reached (NR) with ibrutinib and rituximab and was 67 months (95% CI 63-NR) with fludarabine, cyclophosphamide, and rituximab (hazard ratio 0·44 [95% CI 0·32-0·60]; p<0·0001). The most common grade 3 or 4 adverse event was leukopenia (203 [54%] patients in the fludarabine, cyclophosphamide, and rituximab group and 55 [14%] patients in the ibrutinib and rituximab group. Serious adverse events were reported in 205 (53%) of 384 patients receiving ibrutinib and rituximab compared with 203 (54%) of 378 patients receiving fludarabine, cyclophosphamide, and rituximab. Two deaths in the fludarabine, cyclophosphamide, and rituximab group and three deaths in the ibrutinib and rituximab group were deemed to be probably related to treatment. There were eight sudden unexplained or cardiac deaths in the ibrutinib and rituximab group and two in the fludarabine, cyclophosphamide, and rituximab group. INTERPRETATION: Front line treatment with ibrutinib and rituximab significantly improved progression-free survival compared with fludarabine, cyclophosphamide, and rituximab but did not improve overall survival. A small number of sudden unexplained or cardiac deaths in the ibrutinib and rituximab group were observed largely among patients with existing hypertension or history of cardiac disorder. FUNDING: Cancer Research UK and Janssen.

Venetoclax ramp-up strategies for chronic lymphocytic leukaemia in the United Kingdom: a real world multicentre retrospective study.

This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp-up in 170 patients with chronic lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high-risk patients, four occurred at 20 mg dose and three at the 6-h time-point. Inpatient versus outpatient TLS rates within the high-risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high-risk cohorts. These observations require confirmation in larger studies.

Fisioterapia em crianças com paralisia cerebral no Brasil: uma revisão de escopo.

OBJETIVO: Identificar e avaliar os estudos publicados sobre fisioterapia em crianças e adolescentes brasileiros com paralisia cerebral (PC), usando o modelo da Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF). MÉTODO: Artigos em inglês e português publicados até outubro de 2020, sem restrição de data, foram pesquisados em diferentes bases bibliográficas. Foram extraídos dados sobre as características do estudo, métricas do periódico, características da amostra, domínios da CIF explorados a partir dos componentes e desfechos das intervenções. Para caracterizar as evidências, os estudos foram classificados de acordo com os níveis de evidência do Centro de Medicina Baseada em Evidência de Oxford. RESULTADOS: Noventa e quatro estudos foram incluídos. Crianças com PC espástica e com menores limitações nas habilidades motoras grossas foram as mais reportadas; 67% dos estudos apresentaram baixos níveis de evidência e foram publicados em periódicos sem fator de impacto. As três intervenções mais frequentes foram o conceito neuroevolutivo Bobath/terapia do neurodesenvolvimento, a terapia com vestes e a estimulação transcraniana por corrente contínua. Os componentes das intervenções exploraram estruturas e funções do corpo (73,4%), atividade (59,6%) e ambiente (2,1%). Entretanto não exploraram a participação (0%). Os desfechos investigados abordaram atividade (79,8%), estruturas e funções do corpo (67,0%), participação (1%) e ambiente (0%). INTERPRETAÇÃO: Os estudos de intervenções fisioterapêuticas para crianças e adolescentes brasileiros com PC, apresentam maior foco em minimizar deficiências em estruturas e funções do corpo e limitações de atividades. São necessários mais estudos, com melhor nível de evidência e foco ampliado para a participação e os fatores ambientais.

Physical therapy in children with cerebral palsy in Brazil: a scoping review.

AIM: To identify and assess published studies concerning physical therapy in Brazilian children and adolescents with cerebral palsy (CP) using the International Classification of Functioning, Disability and Health (ICF) framework. METHOD: Articles in English and Portuguese published until October 2020, with no date restrictions, were searched in several different databases. Study characteristics, journal metrics, sample characteristics, and ICF domains explored intervention components and outcomes were extracted. Studies were classified according to the Oxford Centre for Evidence-Based Medicine hierarchy levels to characterize the evidence. RESULTS: Ninety-four studies were included. Spastic CP with fewer limitations in gross motor abilities was the most reported; 67% of the studies had low levels of evidence and were published in journals without an impact factor. The three most frequent interventions were neurodevelopmental treatment, suit therapy, and transcranial direct current stimulation. Intervention components explored body functions and structures (73.4%), activity (59.6%), environment (2.1%). They did not explore participation (0%). The outcomes investigated addressed activity (79.8%), body functions and structures (67.0%), and participation (1.1%), but not environment (0%). INTERPRETATION: Studies of physical therapy for Brazilian children and adolescents with CP focused on reducing impairments and activity limitations. Studies with higher levels of evidence and an expanded focus on participation and environmental factors are necessary.

Analysis of Informative Content on Cerebral Palsy Presented in Brazilian-Portuguese YouTube Videos.

Aims: To describe the characteristics of the most accessed YouTube videos in Brazilian-Portuguese on cerebral palsy (CP), and to analyze content of informational videos about this topic.Methods: This was a cross-sectional study. Searching on YouTube website was conducted by two independent examiners between November and December 2019, using the keywords "Paralisia Cerebral" sorted by videos' number of views. Videos that did not present content related to CP or duplicate videos were excluded. The interaction parameters and content characteristics of the included videos were extracted. To access the trustworthiness and quality of informational videos, the modified Discern checklist and the Global Quality Score was used.Results: Following the eligibility criteria 90 videos were included. Fifty-three (53) were classified as experiential videos and 37 as informational videos. Informational videos presented multi-topics about different aspects of CP. This group of videos presented moderate trustworthiness due to the lack of scientific evidence content. Informational videos had good quality and generally good flow.Conclusion: YouTube presented a large number of videos about CP in Brazilian-Portuguese. Informational videos are useful for patients and healthcare providers; however, it is necessary to included information about scientific evidence, as a strategy to facilitate and promote knowledge translation.

Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma.

The proteasome inhibitor, bortezomib, potentially increases cell sensitivity to chemotherapy. This study was performed to determine the overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) compared to CHOP + bortezomib chemotherapy in mantle cell lymphoma (MCL) patients at first relapse. Forty-six patients were randomly assigned to standard dose CHOP ± bortezomib 1·6 mg/m(2) given on a 21-d cycle for up to eight cycles of treatment. Median age was 71 years (CHOP arm) and 69 years (CHOP-bortezomib arm). Median Eastern Cooperative Oncology Group performance status was 1 (CHOP) and 0 (CHOP-bortezomib) with 65% and 52%, respectively, having a disease stage of IV. ORR was 47·8% (CHOP) and 82·6% (CHOP-bortezomib). Complete response rate was 21·7% (CHOP) vs. 34·8% (CHOP-bortezomib); partial response rate was 26·1% (CHOP) vs. 47·8% (CHOP-bortezomib). Median OS was 11·8 months (CHOP) and 35·6 months (CHOP-bortezomib) (P = 0·01, Hazard ratio [HR] 0·37 [95% confidence interval (CI) 0·16-0·83)] and there was a non-significant improvement in PFS: 8·1 months (CHOP) and 16·5 months (CHOP-bortezomib) [P = 0·12, HR 0·60 (95% CI 0·31-1·15)]. Severe (≥grade 3) sensory neuropathy was similar in both arms (4·3% CHOP vs. 6·5% CHOP-bortezomib). We conclude that the addition of bortezomib to CHOP chemotherapy for relapsed MCL significantly improves outcome with a manageable increase in toxicity.

Translation and measurement properties of the Portuguese-Brazil version of the Hammersmith Infant Neurological Examination (HINE-Br).

OBJECTIVE: The current study aimed to translate the Hammersmith Infant Neurological Examination (HINE) into Brazilian Portuguese and analyze the reliability of the translated version for a population of Brazilian infants. METHODS: This was a methodological study, approved by the Ethics Committee, carried out between June 2020 and May 2021. HINE is a standardized clinical neurological examination used for the early detection of cerebral palsy. The quantitative section, "neurological examination", contains 26 items scored from 0 to 3 points, divided into five categories: cranial nerve function, posture, movements, muscle tone and reflexes, and reactions. The HINE translation followed four steps: translation, synthesis, back-translation, and evaluation by an expert committee. To verify the reliability of the HINE-Br (Portuguese-Brazil version) two independent examiners evaluated 43 infants, between 3 and 22 months of age. Internal consistency was verified by Cronbach's Alpha coefficient and interrater reliability by the intraclass correlation coefficient (ICC). RESULTS: The translated version was similar to the original version and a few semantic and idiomatic adjustments were necessary. Appropriate internal consistency (Alpha=0.91) was found for the 26 items of the HINE-Br, as well as strong interrater reliability for the total score (ICC2.1=0.95), and also for the five categories (ICC2.1=0.83-0.95). CONCLUSIONS: The HINE-Br presents adequate rates of internal consistency and interrater reliability, and can be used for the evaluation of children at risk for cerebral palsy, between 3 and 24 months of age, by pediatricians and pediatric physical therapists.

Abnormal serum free light chain ratio predicts poor overall survival in mantle cell lymphoma.

Serum free light Chain (sFLC) ratios have been correlated with survival outcomes in Hodgkin and non-Hodgkin lymphoma subtypes. This study was undertaken to investigate the prognostic impact of abnormal sFLC ratios in mantle cell lymphoma (MCL). two patient cohorts were analysed for sFLC parameters: a preliminary retrospective cohort and a uniformly treated cohort of 20 relapsed/refractory MCL patients, enrolled in a phase II clinical trial of single agent lenalidomide treatment. 52% of patients had an abnormality of one or more sFLC parameter (71% of the first cohort and 40% of the second cohort). In cohort two, a high baseline SFLC ratio correlated with poorer overall survival (OS) compared to a low/normal ratio (median OS: 1·4 months vs. 19 months respectively; P = 0·001). For patients presenting with an elevated sFLC ratio at trial entry a rise of >35% in the sFLC ratio correlated with disease progression and a sFLC ratio of >2× normal at trial entry correlated with aggressive disease. These data are the first to show a clear clinical correlation between sFLC ratios and survival outcomes in a uniformly treated cohort of MCL patients. We suggest that these markers may be useful in managing patients with MCL in the future.

Symptomatic Thyroglossal Duct Cyst Presenting With Synchronous and Localized Tongue Base Extranodal Mantle Cell Lymphoma. A Unique Case Report Demonstrating Lymphoma Colonization of Cyst Wall, Potentially Relating to a Persistent Embryological Foramen Cecum Remnant.

A 77-year-old male presented with a progressively enlarging midline neck mass. On further investigation he was found to have synchronous thyroglossal duct cyst and extranodal mantle cell lymphoma (MCL) localized to the base of tongue. Both pathologies were managed simultaneously with a surgical approach and the patient remained in clinical remission at the time of publication without indication for systemic oncological treatment. Histology revealed primary extranodal nonblastoid MCL forming a base of tongue mass, with colonization of the thyroglossal duct cyst. Lymphoma was also found in the epithelium of a crypt-like tract traversing one of the tongue base tumor sections. This tract was anatomically and histologically consistent with documented descriptions of the foramen cecum. This case report illustrates a previously undescribed temporal, clinical, and histological association between a base of tongue MCL and symptomatic thyroglossal duct cyst. We provide evidence for a potential causal relationship for the presentation of the thyroglossal duct cyst as a result of oropharyngeal MCL, in the absence of clinical and histological evidence of disseminated disease, directly infiltrating from its tongue base origin to the infrahyoid neck region, potentially via an embryologic foramen cecum remnant. We also highlight the crucial role of the histopathologist in multidisciplinary clinicopathological discussion in demonstrating how fundamental embryological and microanatomical relationships can unite apparently separate diseases.

Antimutagenic potential of Solanum lycocarpum against induction of chromosomal aberrations in V79 cells and micronuclei in mice by doxorubicin.

Solanum lycocarpum A. St. Hil. (Solanaceae) is a hairy shrub or small much-branched tree of the Brazilian Cerrado. S. lycocarpum fruits are commonly used in traditional medicine in powder form or as folk preparations for the treatment of diabetes and obesity, as well as for controlling cholesterol levels. The aim of the present study was to chemically characterize the hydroalcoholic extract (SL) of S. lycocarpum by determination of total flavonoids and total poyphenols and quantification of steroidal alkaloids, as well as to evaluate its mutagenic and/or antimutagenic potential on V79 cells and Swiss mice using chromosomal aberrations and bone marrow micronucleus assays, respectively. Three concentrations of SL (16, 32, and 24 µg/mL) were used for the evaluation of its mutagenic potential in V79 cells and four doses (0.25, 0.50, 1.0, and 2.0 g/kg body weight) were used for Swiss mice. In the antimutagenicity assays, the different concentrations of SL were combined with the chemotherapeutic agent doxorubicin (DXR). HPLC analysis of SL gave contents of 6.57 % ± 0.41 of solasonine and 4.60 % ± 0.40 of solamargine. Total flavonoids and polyphenols contents in SL were 0.04 and 3.60 %, respectively. The results showed that not only SL exerted no mutagenic effect, but it also significantly reduced the frequency of chromosomal aberrations induced by DXR in both V79 cells and micronuclei in Swiss mice at the doses tested.

Assessment of the mutagenic activity of extracts of brazilian propolis in topical pharmaceutical formulations on Mammalian cells in vitro and in vivo.

Propolis possesses various biological activities such as antibacterial, antifungal, anti-inflammatory, anesthetic and antioxidant properties. A topically applied product based on Brazilian green propolis was developed for the treatment of burns. For such substance to be used more safely in future clinical applications, the present study evaluated the mutagenic potential of topical formulations supplemented with green propolis extract (1.2, 2.4 and 3.6%) based on the analysis of chromosomal aberrations and of micronuclei. In the in vitro studies, 3-h pulse (G(1) phase of the cell cycle) and continuous (20 h) treatments were performed. In the in vivo assessment, the animals were injured on the back and then submitted to acute (24 h), subacute (7 days) and subchronic (30 days) treatments consisting of daily dermal applications of gels containing different concentrations of propolis. Similar frequencies of chromosomal aberrations were observed for cultures submitted to 3-h pulse and continuous treatment with gels containing different propolis concentrations and cultures not submitted to any treatment. However, in the continuous treatment cultures treated with the 3.6% propolis gel presented significantly lower mitotic indices than the negative control. No statistically significant differences in the frequencies of micronuclei were observed between animals treated with gels containing different concentrations of propolis and the negative control for the three treatment times. Under the present conditions, topical formulations containing different concentrations of green propolis used for the treatment of burns showed no mutagenic effect in either test system, but 3.6% propolis gel was found to be cytotoxic in the in vitro test.

An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.

Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.

Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes.

Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1G93A model of ALS. BMMCs were isolated from non-transgenic, age matched animals and administered intravenously (IV), intramuscularly (IM), and intravenously and intramuscular concomitantly (IV + IM). BMMC therapy had no significant beneficial effects when injected IV or IM, but delayed disease progression when these two routes were used concomitantly. BMMC IV + IM treatment reduced the number of microglia cells in the spinal cord and partially protected of neuromuscular-junction innervation, but had no effect in preventing motor-neuron loss. This study showed that injection of BMMC IV + IM had better results when compared to each route in isolation, highlighting the importance of targeting multiple anatomical regions in the treatment of ALS.

Translation and measurement properties of the Portuguese-Brazil version of the Hammersmith Infant Neurological Examination (HINE-Br) / Tradução e propriedades de medida da versão Português-Brasil do Hammersmith Infant Neurological Examination (HINE-Br)

ABSTRACT Objective: The current study aimed to translate the Hammersmith Infant Neurological Examination (HINE) into Brazilian Portuguese and analyze the reliability of the translated version for a population of Brazilian infants. Methods: This was a methodological study, approved by the Ethics Committee, carried out between June 2020 and May 2021. HINE is a standardized clinical neurological examination used for the early detection of cerebral palsy. The quantitative section, "neurological examination", contains 26 items scored from 0 to 3 points, divided into five categories: cranial nerve function, posture, movements, muscle tone and reflexes, and reactions. The HINE translation followed four steps: translation, synthesis, back-translation, and evaluation by an expert committee. To verify the reliability of the HINE-Br (Portuguese-Brazil version) two independent examiners evaluated 43 infants, between 3 and 22 months of age. Internal consistency was verified by Cronbach's Alpha coefficient and interrater reliability by the intraclass correlation coefficient (ICC). Results: The translated version was similar to the original version and a few semantic and idiomatic adjustments were necessary. Appropriate internal consistency (Alpha=0.91) was found for the 26 items of the HINE-Br, as well as strong interrater reliability for the total score (ICC2.1=0.95), and also for the five categories (ICC2.1=0.83-0.95). Conclusions: The HINE-Br presents adequate rates of internal consistency and interrater reliability, and can be used for the evaluation of children at risk for cerebral palsy, between 3 and 24 months of age, by pediatricians and pediatric physical therapists.

RESUMO Objetivo: Traduzir o Hammersmith Infant Neurological Examination (HINE) para o português brasileiro e analisar a confiabilidade da versão traduzida em lactentes brasileiros. Métodos: Estudo metodológico, aprovado por Comitê de Ética, realizado entre junho de 2020 e maio de 2021. O HINE é um exame clínico neurológico padronizado, utilizado para detecção precoce de paralisia cerebral. A seção quantitativa, "exame neurológico", contém 26 itens pontuados de 0 a 3, divididos em 5 categorias: função dos nervos cranianos; postura; movimentos; tônus muscular e reflexos; e reações. A tradução do HINE seguiu quatro etapas: tradução; síntese; retrotradução; e avaliação por um comitê de especialistas. Dois examinadores independentes avaliaram 43 lactentes, entre 3 e 22 meses, utilizando a versão HINE-Br (versão em português brasileiro), para verificar sua confiabilidade. A consistência interna foi verificada pelo coeficiente Alpha de Cronbach e a confiabilidade interexaminadores pelo coeficiente de correlação intraclasse (CCI). Resultados: A versão traduzida foi semelhante à versão original e poucos ajustes semânticos e idiomáticos foram necessários. Encontrou-se consistência interna adequada (Apha=0,91) para os 26 itens do HINE-Br, bem como forte confiabilidade interexaminadores para o escore total (CCI2,1=0,95) e também para as cinco categorias (CCI2,1=0,83-0,95). Conclusões: O HINE-Br apresenta índices adequados de consistência interna e confiabilidade interexaminadores, podendo ser utilizada para avaliação de crianças com risco de apresentar paralisia cerebral, entre 3 e 24 meses de idade, por pediatras e fisioterapeutas infantis.

Ursolic acid and oleanolic acid suppress preneoplastic lesions induced by 1,2-dimethylhydrazine in rat colon.

Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenoid compounds found in plants used in the human diet and in medicinal herbs, in the form of aglycones or as the free acid. These compounds are known for their hepatoprotective, anti-inflammatory, antimicrobial, hypoglycemic, antimutagenic, antioxidant, and antifertility activities. In the present study, we evaluated the effects of UA and OA on the formation of 1,2-dimethyl-hydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon of the male Wistar rat. The animals received subcutaneous (sc) injections of DMH (40 mg/kg body weight) twice a week for two weeks to induce ACF. UA, OA and a mixture of UA and OA were administered to the rats five times a week for four weeks by gavage at doses of 25 mg/kg body weight/day each, during and after DMH treatment. All animals were sacrificed in week 5 for the evaluation of ACF. The results showed a significant reduction in the frequency of ACF in the group treated with the triterpenoid compounds plus DMH when compared to those treated with DMH alone, suggesting that UA and OA suppress the formation of ACF and have a protective effect against colon carcinogenesis.

Antimutagenicity of rosmarinic acid in Swiss mice evaluated by the micronucleus assay.

Rosmarinic acid (RA) is a natural phenolic compound which presents different biological activities such as antitumor, antibacterial, anti-inflammatory, hepatoprotective and cardioprotective properties. In view of its important biological activities, the study of the effects of RA on genetic material becomes relevant. Thus, the objective of the present study was to evaluate the mutagenic and/or antimutagenic potential of RA on peripheral blood cells of Swiss mice using the micronucleus assay. Three doses of RA (50, 100 and 200 mg/kg body weight, b.w.) were used for the evaluation of its mutagenic potential. In the antimutagenicity assays, the different concentrations of RA were combined with the chemotherapeutic agent doxorubicin (DXR, 15 mg/kg b.w.). Peripheral blood samples were collected 24, 48 and 72 h after treatment for the evaluation of micronucleated polychromatic erythrocytes (MNPCEs). The results of the mutagenicity assays showed no increase in the frequency of micronuclei in animals treated with different concentrations of RA when compared to the negative controls. Treatment with different concentrations of RA combined with DXR revealed a significant reduction in the frequency of micronuclei compared to animals treated with DXR only. Although the mechanisms underlying the protective effect of RA are not completely understood, the putative antioxidant activity of RA might explain its effect on DXR mutagenicity.

Efeito da intervenção motora domiciliar centrada na família para a funcionalidade de indivíduos com Duchenne / Effect of family-centered home motor intervention on the functioning of individuals with Duchenne

RESUMO O objetivo foi investigar o impacto de um Programa de Intervenção Motora Domiciliar (PIMD), com a abordagem centrada na família, na funcionalidade de indivíduos com Distrofia Muscular de Duchenne (DMD). Foi realizado uma série de casos, entre novembro de 2020 a junho de 2021 e aplicado a função motora grossa dos membros superiores e inferiores antes e após o PIMD, durante 16 sessões. Permaneceram seis crianças entre 12-13 (±2,90) anos de idade; 9,14 (±0,90) anos para perda de deambulação e 6,38 (±1,06) anos para idade de diagnóstico. A Medida da Função Motora inicial foi 47,8 (±20,13) e final, 56 (±20,53); na Escala de Vignos, inicial foi 7 (±1,73) e final, 6,4 (±1,95); na Escala de Brooke, inicial foi 2,0 (±1,30) e final, 2,2 (±1,22); na Performance of the Upper Limb, inicial foi 28,29 (±11,94) e final, 35 (±13,28). Na criança deambuladora, a média do escore de North Star Ambulatory Assessment (NSAA) total inicial foi 25 e final, 27. Portanto, o PIMD pode ser uma alternativa para prolongar a funcionalidade do curso clínico da DMD, em períodos sem intervenção presencial. A telerreabilitação é uma estratégia promissora, entretanto, é necessário treinamento da equipe de cuidados à saúde e o envolvimento dos pais.

ABSTRACT The objective was to investigate the impact of a Home Motor Intervention Program (PIMD), with a family-centered approach, on the functionality of individuals with Duchenne Muscular Dystrophy (DMD). A series of cases was carried out between November 2020 and June 2021 and applied to the gross motor function of the upper and lower limbs before and after PIMD, during 16 sessions. Six children between 12-13 (±2.90) years of age remained; 9.14 (±0.90) years for loss of ambulation and 6.38 (±1.06) years for age at diagnosis. The initial Motor Function Measure was 47.8 (±20.13) and final, 56 (±20.53); on the Vignos Scale, initial was 7 (±1.73) and final, 6.4 (±1.95); on the Brooke Scale, initial was 2.0 (±1.30) and final, 2.2 (±1.22); in the Performance of the Upper Limb, initial was 28.29 (±11.94) and final, 35 (±13.28). In the ambulatory child, the initial total North Star Ambulatory Assessment (NSAA) mean score was 25 and the final score was 27. Therefore, PIMD can be an alternative to prolong the functionality of the clinical course of DMD, in periods without face-to-face intervention. Telerehabilitation is a promising strategy, however, training of the health care team and parental involvement is required.