Single-domain antibodies applied as antiviral immunotherapeutics.

Viral infections have been the cause of high mortality rates throughout different periods in history. Over the last two decades, outbreaks caused by zoonotic diseases and transmitted by arboviruses have had a significant impact on human health. The emergence of viral infections in different parts of the world encourages the search for new inputs to fight pathologies of viral origin. Antibodies represent the predominant class of new drugs developed in recent years and approved for the treatment of various human diseases, including cancer, autoimmune and infectious diseases. A promising group of antibodies are single-domain antibodies derived from camelid heavy chain immunoglobulins, or VHHs, are biomolecules with nanometric dimensions and unique pharmaceutical and biophysical properties that can be used in the diagnosis and immunotherapy of viral infections. For viral neutralization to occur, VHHs can act in different stages of the viral cycle, including the actual inhibition of infection, to hindering viral replication or assembly. This review article addresses advances involving the use of VHHs in therapeutic propositions aimed to battle different viruses that affect human health.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects.

OBJECTIVE: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. METHOD: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. RESULTS: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007.  Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. CONCLUSIONS: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects

Abstract Objective: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. Method: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. Results: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007. Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. Conclusions: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Apalutamide and autophagy inhibition in a xenograft mouse model of human prostate cancer.

BACKGROUND: Apalutamide (APA) is a next-generation androgen receptor antagonist for the treatment of advanced prostate cancer. We have previously shown that upregulation of autophagy is one of the mechanisms by which prostate cancer (PC) cells survive APA anti-tumor treatment in vitro. Therefore, we investigated the characteristics of the autophagic response to APA treatment, alone and in combination with autophagy inhibition, in an in vivo model. METHODS: Tumor cells were injected into previously castrated nude mice. Four groups of mice bearing LNCaP xenografts were treated with daily intraperitoneal (i.p.) injections of vehicle (control), APA (10 mg/kg), APA (10 mg/kg) + Chl (Chloroquine, 10 mg/kg) or Chl (10 mg/kg). The animals of each treatment group (3/treatment) were kept for the duration of 2 and 3 weeks. At the end of the experiments, the animals were sacrificed and all samples assessed for tumor weight and size, histological analysis, immunoblotting (WES) and immunofluorescence. RESULTS: The tumor weight was significantly reduced in mice treated with APA + Chl (203.2 ± 5.0, SEM, P = 0.0066) compared to vehicle control (380.4 ± 37.0). Importantly, the combined treatment showed a higher impact on tumor weight than APA (320.4 ± 45.5) or Chl (337.9 ± 35) alone. The mice treated with the combination of APA + Chl exhibited a reduced expression of ATG5 (autophagy-related five protein), Beclin 1 and LC3 punctuations and an increase in P62 as visualized by immunofluorescence and WES. In addition, Ki-67 nuclear staining was detected in all samples however reduced in APA + Chl (58%) compared to vehicle control (100%). The reduction in Ki-67 protein was associated with an increase in caspase 3 and endothelial CD31 protein expression. CONCLUSION: These data demonstrate that a treatment with APA + Chl leads to reduced autophagy levels and to tumor suppression compared to the APA monotherapy. Hence, the increased antitumor effect of APA in combination with autophagy inhibitors might provide a new therapeutic approach potentially translatable to patients.

Resistance to diseases of sour, sweet and wild passion fruit genotypes

The cultivation of passion fruit is important for Brazil, since the country is currently the largest producer and consumer of fruit in the world. However, the fields of passion fruit still face important problems due to the incidence and severity of diseases in the field. Thus, the present study aimed to assess resistance to bacterial and fungal diseases in 13 genotypes of sour, sweet and wild passion fruit, in field conditions in the Distrito Federal, Brazil. For this, a field experiment was installed in a randomized block design, with four replications and 13 treatments (genotypes). The characteristics of incidence, severity and degree of resistance for bacteriosis, septoriosis, scab and anthracnose diseases were evaluated in 5 fruits per plot of each genotype. Genetic parameters of the evaluated traits were also estimated. High heritability values and CVg/Cve ratio were observed for most of the evaluated characteristics. The genotypes presented mean values of incidence and severity of bacteriosis, septoriosis, scab and anthracnose different among them, and the one that presented the best results in the degree of resistance for all diseases was F1 (MAR20 # 24 x ECL7 P1 R4).

Agronomic assessment of 32 sour passionfruit genotypes in federal district

The production of passion fruit is important in Brazil. In order to contribute to the development of the most promising cultivars of passion fruit, this study aimed to evaluate the agronomic performance of 32 genotypes of passion fruit in Federal District of Brazil, and to estimate genetic parameters for use in breeding programs. Thirty-two genotypes were used in a randomized block design, with eight plants per plot and four replications. The experiment was conducted in field. Twenty-eight harvests were performed, and the variables analyzed were: productivity estimated, total number of fruits per hectare, average fruit weight and these characteristics following classification of fruits in five categories. The genotypes that presented the highest total yield estimated were MAR20 # 23, AR 01 and PLANTA 7. For industrial purposes, genotypes MAR 20 # 21 and BRS Gigante Amarelo were superior. For fresh consumption, the genotypes with the best performance were PLANT 7, AR 01 and MSC. Total productivity estimated and total number of fruits per hectare in the first-class classification showed high values of heritability and CVg/CVe ratio. These results indicate a favorable condition for selection.

Camelid Single-Domain Antibodies for the Development of Potent Diagnosis Platforms.

The distinct biophysical and pharmaceutical properties of camelid single-domain antibodies, referred to as VHHs or nanobodies, are associated with their nanometric dimensions, elevated stability, and antigen recognition capacity. These biomolecules can circumvent a number of diagnostic system limitations, especially those related to the size and stability of conventional immunoglobulins currently used in enzyme-linked immunosorbent assays and point-of-care, electrochemical, and imaging assays. In these formats, VHHs are directionally conjugated to different molecules, such as metallic nanoparticles, small peptides, and radioisotopes, which demonstrates their comprehensive versatility. Thus, the application of VHHs in diagnostic systems range from the identification of cancer cells to the detection of degenerative disease biomarkers, viral antigens, bacterial toxins, and insecticides. The improvements of sensitivity and specificity are among the central benefits resulting from the use of VHHs, which are indispensable parameters for high-quality diagnostics. Therefore, this review highlights the main biotechnological advances related to camelid single-domain antibodies and their use in in vitro and in vivo diagnostic approaches for human health.

Impact of short-term Dutasteride treatment on prostate-specific membrane antigen expression in a mouse xenograft model.

BACKGROUND: Dutasteride has been shown to increase expression of the prostate-specific membrane antigen (PSMA) in prostate cancer cells in previous in vitro studies. This 5-alpha-reductase inhibitor is commonly used for the treatment of symptomatic benign prostatic enlargement. The modulation of PSMA expression might affect PSMA-based prostate cancer imaging and therapy. AIM: The purpose of this work was to further analyze concentration-dependent effects of Dutasteride on PSMA expression in a mouse xenograft model. METHODS AND RESULTS: Four groups of mice bearing LNCaP xenografts were treated for 14 days with daily intraperitoneal injections of either vehicle control or different concentrations of Dutasteride (0.1, 1, 10 mg/kg). Total expression of PSMA, androgen receptor (AR), and caspase-3 protein was analyzed using immunoblotting (WES). In addition, PSMA, cleaved caspase-3 and Ki-67 expression was assessed and quantified by immunohistochemistry. Tumor size was measured by caliper on day 7 and 14, tumor weight was assessed following tissue harvesting. The mean PSMA protein expression in mice increased significantly after treatment with 1 mg/kg (10-fold) or 10 mg/kg (sixfold) of Dutasteride compared to vehicle control. The mean fluorescence intensity significantly increased by daily injections of 0.1 mg/kg Dutasteride (1.6-fold) as well as 1 and 10 mg/kg Dutasteride (twofold). While the reduction in tumor volume following treatment with high concentrations of 10 mg/kg Dutasteride was nonsignificant, no changes in AR, caspase-3, cleaved caspase-3, and Ki-67 expression were observed. CONCLUSION: Short-term Dutasteride treatments with concentrations of 1 and 10 mg/kg significantly increase the total PSMA protein expression in a mouse LNCaP xenograft model. PSMA fluorescence intensity increases significantly even using lower daily concentrations of 0.1 mg/kg Dutasteride. Further investigations are needed to elucidate the impact of Dutasteride treatment on PSMA expression in patients.

ALVEOLAR RECRUITMENT MANEUVERS FOR CHILDREN WITH CANCER AND ACUTE RESPIRATORY DISTRESS SYNDROME: A FEASIBILITY STUDY.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) can be a devastating condition in children with cancer and alveolar recruitment maneuvers (ARMs) can theoretically improve oxygenation and survival. The study aimed to assess the feasibility of ARMs in critically ill children with cancer and ARDS. METHODS: We retrospectively analyzed 31 maneuvers in a series of 12 patients (median age of 8.9 years) with solid tumors (n=4), lymphomas (n=2), acute lymphoblastic leukemia (n=2), and acute myeloid leukemia (n=4). Patients received positive end-expiratory pressure from 25 up to 40 cmH20, with a delta pressure of 15 cmH2O for 60 seconds. We assessed blood gases pre- and post-maneuvers, as well as ventilation parameters, vital signs, hemoglobin, clinical signs of pulmonary bleeding, and radiological signs of barotrauma. Pre- and post-values were compared by the Wilcoxon test. RESULTS: Median platelet count was 53,200/mm3. Post-maneuvers, mean arterial pressure decreased more than 20% in two patients, and four needed an increase in vasoactive drugs. Hemoglobin levels remained stable 24 hours after ARMs, and signs of pneumothorax, pneumomediastinum, or subcutaneous emphysema were absent. Fraction of inspired oxygen decreased significantly after ARMs (FiO2; p=0.003). Oxygen partial pressure (PaO2)/FiO2 ratio increased significantly (p=0.0002), and the oxygenation index was reduced (p=0.01), but all these improvements were transient. Recruited patients' 28-day mortality was 58%. CONCLUSIONS: ARMs, although feasible in the context of thrombocytopenia, lead only to transient improvements, and can cause significant hemodynamic instability.

Fruit quality of wild, sweet and yellow passion fruit genotypes in Distrito Federal, Brazil

Despite the importance of passion fruit for the Brazilian fruit market, there are still many agronomic and fruit quality problems to be solved, in order to increase this crop performance. The objective of this study was to evaluate the quality of twelve genotypes of wild, sweet and yellow passion fruit, aiming to identify promising materials considering fruit quality, in Federal District, Brazil. An experiment was carried out at the Água Limpa Farm of the Universidade de Brasília (UnB) from 2016 to 2018, in a randomized block design, with 12 treatments, 4 replicates and 6 plants/plot. At the harvesting time, six fruits per plot were randomly collected for the following physicochemical analysis: fruit mass, pulp mass with and without seeds, length/longitudinal diameter, width/transverse diameter, length/width ratio, husk thickness, predominant color of the pulp (L*, C*, h*), number of seeds, seed size, total soluble solids content, total titratable acidity, total soluble solids/total titratable acidity ratio and pH. High heritability values ​​and relation of genetic/environment variation coefficients ratio were observed for most of the characteristics evaluated. The genotypes of yellow passion fruit MAR20#21 P2 x FB 200 P1 R2 and MAR20#19 ROXO R4 x ECRAM P3 R3 showed the best characteristics of fruit mass and pulp mass with seed. All the genotypes studied showed values ​​of total soluble solids above 11ºBrix. Positive and significant correlation was observed between fruit mass and length/width ratio, indicating that oblong fruits have higher fruit mass.

Alveolar recruitment maneuvers for children with cancer and acute respiratory distress syndrome: a feasibility study / Manobras de recrutamento alveolar em crianças com câncer e síndrome do desconforto respiratório agudo: um estudo de viabilidade

ABSTRACT Objective: Acute respiratory distress syndrome (ARDS) can be a devastating condition in children with cancer and alveolar recruitment maneuvers (ARMs) can theoretically improve oxygenation and survival. The study aimed to assess the feasibility of ARMs in critically ill children with cancer and ARDS. Methods: We retrospectively analyzed 31 maneuvers in a series of 12 patients (median age of 8.9 years) with solid tumors (n=4), lymphomas (n=2), acute lymphoblastic leukemia (n=2), and acute myeloid leukemia (n=4). Patients received positive end-expiratory pressure from 25 up to 40 cmH20, with a delta pressure of 15 cmH2O for 60 seconds. We assessed blood gases pre- and post-maneuvers, as well as ventilation parameters, vital signs, hemoglobin, clinical signs of pulmonary bleeding, and radiological signs of barotrauma. Pre- and post-values were compared by the Wilcoxon test. Results: Median platelet count was 53,200/mm3. Post-maneuvers, mean arterial pressure decreased more than 20% in two patients, and four needed an increase in vasoactive drugs. Hemoglobin levels remained stable 24 hours after ARMs, and signs of pneumothorax, pneumomediastinum, or subcutaneous emphysema were absent. Fraction of inspired oxygen decreased significantly after ARMs (FiO2; p=0.003). Oxygen partial pressure (PaO2)/FiO2 ratio increased significantly (p=0.0002), and the oxygenation index was reduced (p=0.01), but all these improvements were transient. Recruited patients' 28-day mortality was 58%. Conclusions: ARMs, although feasible in the context of thrombocytopenia, lead only to transient improvements, and can cause significant hemodynamic instability.

RESUMO Objetivo: A síndrome do desconforto respiratório agudo (SDRA) pode ser uma condição devastadora em crianças com câncer e as manobras de recrutamento alveolar (MRA) podem melhorar a oxigenação e a sobrevida. O objetivo foi avaliar a viabilidade das MRA em crianças gravemente doentes com câncer e SDRA. Métodos: Analisamos retrospectivamente 31 manobras em 12 pacientes (idade mediana de 8,9 anos), com tumores sólidos (n=4), linfomas (n=2) e leucemias linfoide (n=2) e mieloide agudas (n=4). Os pacientes receberam pressão expiratória final positiva de 25 a 40 cmH20, com delta de pressão de 15 cmH2O por 60 segundos. Gasometrias foram analisadas pré e pós-manobras, bem como os parâmetros de ventilação, sinais vitais, hemoglobina, sinais clínicos de sangramento pulmonar e sinais radiológicos de barotrauma. Valores foram comparados com o teste de Wilcoxon. Resultados: A contagem mediana de plaquetas era de 53.200/mm3. Após as manobras, em dois pacientes, a pressão arterial média declinou mais de 20%, e quatro necessitaram de aumento de drogas vasoativas. A hemoglobina permaneceu estável 24 horas após a MRA, sem sinais de pneumotórax, pneumomediastino ou enfisema subcutâneo. Houve diminuição significativa nas frações inspiradas de oxigênio (FiO2; p=0,003). A relação pressão arterial de oxigênio (PaO2)/FiO2 aumentou (p=0,002), e o índice de oxigenação caiu (p=0,01), mas essas melhoras foram transitórias. A mortalidade em 28 dias foi de 58%. Conclusões: As MRA, embora viáveis no contexto da trombocitopenia, levam apenas a melhorias transitórias e podem causar instabilidade hemodinâmica significativa.

Pulmonary Function in Long-Term Survivors of Childhood and Adolescence Osteosarcoma: Case Report / Função Pulmonar em Sobreviventes de Osteossarcoma da Infância e Adolescência: Relato de Caso / Función Pulmonar en Sobrevivientes de Osteosarcoma en la Infancia y la Adolescencia: Relato de Caso

Introduction: Chemotherapy used in osteosarcoma have the potential to cause lung damage. The objectives were to analyze lung volumes and capacities, and respiratory muscle strength of patients treated with chemotherapy and surgery for osteosarcoma. The study was designed as a prospective case-series of patients, through the analysis of spirometry,impulse, oscillometry, and manovacuometry tests. Case report: In twenty-one patients, the median age at diagnosis was 15 years, and at inclusion, 30 years. The median disease-free survival time was 10 years. Eight different chemotherapeutic agents were used: cisplatin, doxorubicin, methotrexate, carboplatin, ifophosphamide, epidoxorubicin, cyclophosphamide and etoposide. There were test abnormalities in 14 patients (66.6%), with mild obstructive disorders on spirometry in three patients (14.3%), and obstructive patterns on oscillometry in seven patients (33.3%). On spirometry, the mean ± standard deviation (SD) values of forced vital capacity (FVC) were 91.9%±12.2; for forced expiratory volume in one second (FEV1) were 87.4%±12.2 and FEV1/FVC ratios, 95.4%±7.9. On oscillometry, mean ± SD values for resistance at 5 Hz were 126.2%±36.2; for resistance at 20 Hz, 128.4%±32.4; reactance at 5 Hz, -0.75±0.68 kPa/L/s; for resonant frequency, 15.6±4.2 Hz. Nine patients (42.8%) had reduced maximum pressures on the manovacuometry: Maximum Expiratory Pressure (MEP) were reduced in eight patients, and inspiratory (MIP) in three. The mean ± SD MIP was 89.4±29.5; MEP, 88±37.7. Conclusion: Mild abnormalities in pulmonary function tests in this series of patients were observed years after treatment for osteosarcoma

Introdução: A quimioterapia usada no osteossarcoma tem potencial para causar danos aos pulmões. Os objetivos deste trabalho foram analisar os volumes e capacidades pulmonares e a força respiratória de pacientes tratados com quimioterapia e cirurgia para osteossarcoma, em uma série prospectiva de casos, em um hospital pediátrico oncológico, por meio da análise de espirometria, oscilometria de impulso e manovacuometria. Relato de caso: Em 21 pacientes, a mediana de idade ao diagnóstico foi de 15 anos e na inclusão de 30 anos. O tempo médio de sobrevida livre de doença foi de dez anos. Houve alterações nos exames em 14 pacientes (66,6%), com distúrbios obstrutivos leves na espirometria em três pacientes (14,3%) e padrões obstrutivos na oscilometria em sete pacientes (33,3%). Na espirometria, os valores de média ± desvio padrão (DP) da capacidade vital forçada (CVF) foram 91,9%±12,2; para o volume expiratório forçado no primeiro segundo (VEF1) foram 87,4%±12,2 e as relações VEF1/CVF, 95,4%±7,9. Na oscilometria, os valores médios ± DP para resistência em 5 Hz foram 126,2%±36,2; para resistência a 20 Hz, 128,4% ± 32,4; reatância a 5 Hz, -0,75 ± 0,68 kPa/L/s; para frequência de ressonância, 15,6±4,2 Hz. Na manovacuometria, nove pacientes (42,8%) apresentaram redução nas pressões: as pressões expiratórias máximas (PEmáx) foram reduzidas em oito pacientes e as inspiratórias (PImáx) em três. A média ± DP da PImáx foi 89,4±29,5; PEmáx, 88±37,7. Conclusão: Observaram-se alterações leves nos testes de função pulmonar anos após o tratamento do osteossarcoma

Introducción: La quimioterapia utilizada en osteosarcoma puede causar daño a los pulmones. Los objetivos de este trabajo fueron analizar los volúmenes y capacidades pulmonares y la fuerza respiratoria en pacientes tratados para osteosarcoma, en una serie prospectiva de casos, en un hospital de oncología pediátrica, mediante el análisis de espirometría, oscilometría de impulsos y manuvacuometría. Relato de caso: En 21 pacientes, la mediana de edad al diagnóstico fue de 15 años y en la inclusión de 30 años. La supervivência media libre de enfermedad fue de diez años. Hubo alteraciones en los exámenes en 14 pacientes (66,6%), con alteraciones obstructivas leves en la espirometría en tres (14,3%), y obstrucción en la oscilometría en siete (33,3%). En espirometría, las medias ± desviación estándar (DE) de la capacidad vital forzada (CVF) fueron 91,9%±12,2; para el volumen espiratorio forzado en el primer segundo (VEF1) fue 87,4%±12,2 y el cociente VEF1/CVF fue 95,4%±7,9. En oscilometría, los valores medios ± DE para la resistencia a 5 Hz fueron 126,2%±36,2; para resistencia a 20 Hz, 128,4%±32,4; reactancia a 5 Hz, -0,75±0,68 kPa/L/s; para la frecuencia de resonancia, 15,6±4,2 Hz. En manuvacuometría, nueve pacientes (42,8%) mostraron una reducción de las presiones: las presiones espiratorias máximas (PEmáx) se redujeron en ocho pacientes y las presiones inspiratorias (PImáx) en tres. La media ± DE del PImáx fue 89,4 ± 29,5; PEmáx, 88±37,7. Conclusión: Se observaron ligeros cambios en las pruebas de función pulmonar años después del tratamiento del osteosarcoma

Genetic parameters estimate for plant characters of a particular carrot population in two different agroecologic cultivation systems / Parâmetros genéticos estimados para caracteres de planta de uma população particular de cenoura em dois sistemas de cultivo agroecológico diferentes

Carrots are among the most planted vegetables in Brazil, which represents importance in the national market. This crop can be grown in conventional and agroecological systems, and studies to improve productivity, disease resistance and root quality in agroecological cropping systems are important. The aim of the present work was to estimate genetic parameters that provide a breeding strategy in the search for the development of new varieties of carrot adapted to the conditions of Distrito Federal's agroecology cultivation. Considering data from tests performed in areas of agroecology cultivation (Natural Agriculture-NA and Organic Agriculture-OA), the following characteristics were evaluated: incidence of leaf blight-LB, incidence of root cracking-CRACK, root length-COMP, format of root tip-TP, format of root shoulder-TO, measure of the color of the a* xylem parameter-a*X, measure of the color of the a* phloem parameter-a*F. Traits were evaluated in 100 half-sib progenies derived from Brasília cultivar, using a completely randomized block design. For the characters COMP, a*X, a*F, TP and TO, the treatment X environment interaction was significant according to the results from test F. The values of the individual variance analyses presented significant effect for the following characteristics: COMP, a*X, TP, TO, LB for NA system, and COMP, a*X, a*F, TP for OA system. In NA system, the values of heritability estimates-ha² for the plant characters fluctuated from 65.66 to 25.52% and, in the OA system, the ha² of the characters a*X, was 81.13%. Estimates of genetic gain per cycle for the characters a*X and a*F were lower in NA system than the estimates observed in OA system.

A cenoura está entre as hortaliças mais plantadas no Brasil, o que representa importância no mercado nacional. Essa cultura pode ser cultivada em sistemas convencionais e agroecológicos, sendo importante o desenvolvimento de estudos para melhorar características de produtividade, resistência a doenças e qualidade de raiz em sistemas com base agroecológica de cultivo. O objetivo do presente trabalho foi estimar parâmetros genéticos que fornecem uma estratégia de melhoramento na busca pelo desenvolvimento de novas variedades de cenoura adaptadas às condições do cultivo agroecológico do Distrito Federal. Considerando dados de testes realizados em áreas de cultivo agroecológico (Agricultura Natural - NA e Agricultura Orgânica - OA), foram avaliadas as seguintes características: incidência de queima das folhas - LB, incidência de rachadura radicular - RACH, comprimento de raiz - COMP, formato de raiz -TP, formato do ombro -TO, medida da cor do parâmetro a * do xilema ­ a*X, medida da cor do parâmetro a *do floema ­ a*F. As características foram avaliadas em 100 progênies de meios-irmãos derivadas da cultivar Brasília, usando um delineamento de blocos inteiramente casualizados. Para os caracteres COMP, a*X, a*F, TP e TO, a interação tratamento X ambiente foi significativa de acordo com os resultados do teste F. Os valores das análises de variância individuais apresentaram efeito significativo para as seguintes características: COMP, a*X, TP, TO, LB para o sistema NA e COMP, a*X, um a*F, TP para o sistema OA. No sistema NA, os valores de estimativa de herdabilidade - ha² para os caracteres da planta variaram de 65,66 a 25,52% e, no sistema OA, o ha² da característica a*X foi de 81,13%. As estimativas de ganho genético por ciclo para os caracteres a*X e a*F foram menores no sistema NA do que as estimativas observadas no sistema OA.

Morphoagronomic characterization of sweet potato accessions from the germplasm bank of Embrapa hortaliças / Caracterização morfológica de acessos de batata-doce mantidos no banco de germoplasma da Embrapa Hortaliças

Studies on the determination of genetic divergence among genotypes are important tools in breeding programs, contributing to the identification of parents with considerable productive potential. However, little is known about the combinatorial capacity of sweet potato (Ipomoea batatas) accessions and its adaptation to the different regions of Brazil. The objective of this study was to evaluate the morpho-agronomic traits from 102 sweet potato accessions from the Germplasm Bank of Embrapa Hortaliças. The experiment was laid out as an augmented block design comprised of 102 treatments. Nineteen above ground traits were measured using descriptors for the respective parts. Estimated values of broad sense heritability were high for the traits mean branch length (95.75%), immature leaf color (85.06%), and predominant branch color (90.57%). Coefficients of environmental variation were below 30.00% for all variables, except for branch weight (51.62%). The 102 clones analyzed presented broad genetic variability for the different traits evaluated, especially for branch weight, and branch length, and mature leaf color.

Estudos de determinação de divergência genética entre genótipos são ferramentas de grande importância em programas de melhoramento, auxiliando na identificação de genitores com considerável potencial produtivo. No entanto, pouco ainda se sabe sobre a capacidade combinatória de acessos de batata-doce (Ipomoea batatas) e sobre a adaptação a diferentes regiões do Brasil. O objetivo deste trabalho foi avaliar características agronômicas de 102 acessos de batata-doce mantidos no Banco de Germoplasma da Embrapa Hortaliças. O experimento foi instalado utilizando o delineamento em blocos aumentados, com 102 tratamentos. Foram mensuradas 19 características da parte aérea utilizando-se descritores das respectivas partes. Os valores das estimativas de herdabilidade no sentido amplo foram altos para as características comprimento médio das ramas (95,75%), cor da folha imatura (85,06%) e cor predominante da rama (90,57%). Os coeficientes de variação foram inferiores a 30 % para todas as variáveis, exceto para peso das ramas (51.62%). Os 102 clones analisados apresentaram ampla variabilidade genética para as diferentes características avaliadas, principalmente para peso das ramas, comprimento das ramas e cor da folha madura

Effects of a 12-week resistance and aerobic exercise program on muscular strength and quality of life in breast cancer survivors: Study protocol for the EFICAN randomized controlled trial.

BACKGROUND: The number of people living with the side effects of breast cancer treatment (eg, loss of muscular mass and muscular strength, upper-limb mobility and disability, lymphedema, cardiac toxicity, and reduced quality of life) is increasing yearly. These consequences can be improved through exercise, specially combining resistance and aerobic training. Previous exercise trials have not been consistent in applying training principles and standardized reporting, and this partly explains the variability in obtained results. The aim of this study is to assess the effect of a 12-week supervised resistance exercise program combined with home-based aerobic exercise, compared with home-based aerobic exercise only, on muscular strength and several aspects of health-related quality of life in breast cancer survivors. To maximize transparency, replicability, and clinical applicability, the intervention is described following the consensus on exercise reporting template. METHODS: This study is a parallel-group randomized controlled trial in which 60 female breast cancer survivors, who have completed central treatments of the disease in the last 5 years, will be randomly assigned to either an experimental group that will perform a total of 24 progressive resistance training sessions for 12 weeks (ie, 2 weeks of individual training and 10 weeks of micro-group training) and will be requested to undertake 10,000 steps/d, or a control group that will be requested to undertake 10,000 steps/d, only. Outcomes will be evaluated at baseline and at week 12. Primary outcome measure is peak isometric muscular strength of the lower- and upper-body, assessed with several exercises through an electromechanical dynamometer. Secondary outcomes include cardiorespiratory fitness, upper-joint mobility and disability, health-related quality of life, cancer-related fatigue, depression, life satisfaction, and presence of lymphedema. DISCUSSION: This study aims to investigate the extent to which a 12-week supervised and progressive resistance exercise program, in addition to home-based aerobic physical activity, might improve muscular strength and health-related quality of life in breast cancer survivors. The comprehensive description of the intervention will likely contribute to enhancing exercise prescription in this population. TRIAL REGISTRATION NUMBER: ISRCTN14601208.

The management of academic supervision in the More Doctors for Brazil Project by higher education institutions / A gestão da supervisão acadêmica no Projeto Mais Médicos para o Brasil por instituições de educação superior / La gestión de la supervisión académica en el Proyecto Más Médicos para Brasil por las instituciones de educación superior

ABSTRACT The More Doctors Program is a strategic set of actions for the Brazilian National Health System (SUS) aiming at improvements in medical education, professional qualification and retention of doctors in unassisted areas. Among these actions, we highlight the Project More Doctors for Brazil (PMMB), responsible for the emergency supply of doctors. It was conceived as a response to the shortage of professionals in primary care across the country, an extremely important aspect in this set of strategies for SUS. The professional improvement proposed by PMMB has mobilized public higher education institutions to participate as supervisory institutions. They are responsible for supervising the activities developed by doctors and for strengthening the continuing education policy through teaching-service integration actions. This article aims to report on the experience of managing academic supervision in light of the challenge of the implementation of PMMB.

RESUMO O Programa Mais Médicos (PMM) consagra-se como um conjunto estratégico de ações para o Sistema Único de Saúde (SUS), visando ao aprimoramento da formação médica, à qualificação profissional e à fixação de médicos em regiões desassistidas. Destacamos, dentre essas ações do programa, o Projeto Mais Médicos para o Brasil (PMMB), responsável pelo provimento emergencial de médicos. Este foi concebido como resposta à carência de profissionais na Atenção Básica em Saúde do país, aspecto de destaque nesse conjunto de estratégias para o SUS. O aperfeiçoamento proposto pelo PMMB mobilizou as instituições públicas de educação superior a atuar como instituições supervisoras (IS). Essas instituições atuam na supervisão das atividades desenvolvidas pelos médicos e no fortalecimento da política de educação permanente com ações de integração ensino-serviço. Este estudo objetiva relatar a experiência na gestão da supervisão acadêmica diante do desafio de implantação do PMMB.

RESUMEN El Programa Más Médicos se consagra como un conjunto estratégico de acciones para el Sistema Único de Salud (SUS) teniendo como objetivo el perfeccionamiento de la formación médica, de la calificación profesional y el establecimiento de médicos en regiones no asistidas. Entre esas acciones del Programa, subrayamos el Proyecto Más Médicos para Brasil (PMMB), responsable por la provisión de médicos en situación de emergencia. El mismo fue concebido como respuesta a la carencia de profesionales en la Atención Básica de Salud del país, aspecto de destaque en ese conjunto de estrategias para el SUS. El perfeccionamiento propuesto por el PMMB movilizó a las instituciones públicas de educación superior para que actuaran como Instituciones Supervisoras (IS). Estas instituciones actúan en la supervisión de las actividades desarrolladas por los médicos y en el fortalecimiento de la política de educación permanente con acciones de integración enseñanza-servicio. Este estudio tiene el objetivo de relatar la experiencia en la gestión de la Supervisión Académica ante el desafío de implantación del PMMB.

Ornamental potential of sweet potato accessions / Potencial ornamental de acessos de batata-doce

Sweet potato [Ipomoea batatas (L.) Lam.] is a multipurpose plant due to the different uses for its roots, leaves, and branches. The objective of this study was to evaluate the ornamental potential of sweet potato accessions from the Germplasm Bank of Embrapa Hortaliças, Brasilia, DF, Brazil. The morphological characterization and evaluation of the ornamental potential used five accessions with distinct leaf shape (CNPH 980, CNPH 1205, CNPH 895, CNPH 796, CNPH 1284) and 12 qualitative and quantitative descriptors [plant type (PT), leaf lobe type (LLT), immature leaf color (ILC), leaf lobe number (LLN), branch color (BC), shape of central leaf lobe (SCLL), petiole pigmentation (PP), mature leaf size (MLS), mature leaf color (MLC), leaf shape (LS), branch yield (BY), and root yield (RY)]. In the evaluation of the ornamental potential, each criterion was scored from 10 (minimum) to 100 (maximum). Leaf lobe number was the trait that pleased the evaluators the most, and the greater the number of lobes, the greater was the ornamental potential. CNPH 980, CNPH 1205, and CNPH 1284 stood out for this trait. CNPH 1284 (almost divided leaf type) had the greatest score and was considered, by the evaluators, as the accession with the most harmonious aesthetics, indicating a great ornamental potential for the consumer market. All accessions studied presented considerable ornamental potential and could be used in floral arrangements or garden beds.

A batata-doce [Ipomoea batatas (L.) Lam.] é uma planta com diferentes aptidões de uso das suas raízes, folhas e hastes. O objetivo deste trabalho foi avaliar o potencial ornamental de acessos de batata-doce oriundas do banco de germoplasma mantidos na Embrapa Hortaliças, Brasília, DF, Brasil. Para a caracterização morfológica e avaliação do potencial ornamental, foram escolhidos cinco acessos com formatos de folhas diferentes (CNPH 980, CNPH 1205, CNPH 895, CNPH 796, CNPH 1284) e utilizados doze descritores qualitativos e quantitativos [tipo de planta (TP), tipo de lóbulo da folha (TLF), cor da folha imatura (CFI), número de lóbulos por folha (NLF), cor das ramas (CR), formato do lóbulo central (FLC), pigmento no pecíolo (PP), tamanho da folha madura (TFM), cor da folha madura (CFM), formato da folha (FF), produção de ramas (BY) e produção de raízes (RY)]. Na avaliação do potencial ornamental, cada critério foi pontuado por meio de notas variando de 10 (mínimo) a 100 (máximo). A característica número de lóbulos da folha foi a que mais agradou os avaliadores. Observou-se que quanto mais lóbulos, maior o potencial ornamental, sendo que os acessos CNPH 980, CNPH 1205 e CNPH 1284 se destacaram para essa característica. CNPH 1284, com folhas no formato quase dividido, obteve a maior nota e foi considerado como o acesso com a estética mais harmoniosa, indicando grande potencial ornamental para o mercado consumidor, na opinião dos avaliadores. Os cinco acessos estudados apresentaram considerável potencial ornamental, podendo ser usados como forragem, complementos para arranjos florais ou como jardineiras.

Effect of organic silicon, methylsulfonylmethane, and glucosamine sulfate in mandibular bone defects in rats.

Organic silicon (OS), glucosamine sulfate (GS), and methylsulfonylmethane (MSM) have been related to bone and connective tissue health and have been considered as basic therapy for osteoarthrosis disorders. Therefore, the aim was to analyze the effect of the association of these three components in mandibular bone defects in rats. Nine rats were used for histocompatibility test. In each animal was implanted the composition (70% OS, 15% GS, 15% MSM) and gutta percha (control) under the dorsal subcutaneous tissue. The samples were collected at 7, 14, and 21 days post-surgery and inflammatory events analyzed. In sequence, the composition was engrafted in mandibular bone defects of nine rats; bone defects without treatment were the control group. Analyses were performed at 7, 14, and 28 days post-surgery and samples were evaluated by scanning electron microscopy (SEM). For the histocompatibility test, both groups had a moderate inflammatory process at 7 days post-surgery and mild inflammatory process at 14 and 21 days. But in SEM analysis, the composition promotes an extensive reabsorption in cortical and crest alveolar bone, and great tooth root reabsorption. In conclusion, although the composition had positive result in the histocompatibility test, its direct application in mandibular bone defects caused intense resorption.

Polyacrylic acid coated and non-coated iron oxide nanoparticles are not genotoxic to human T lymphocytes.

The use of iron oxide nanoparticles (ION) for diagnostic and therapeutic purposes requires a clear favorable risk-benefit ratio. This work was performed with the aim of studying the ability of polyacrylic acid (PAA)-coated and non-coated ION to induce genotoxicity in human T lymphocytes. For that purpose, their influence on cell cycle progression and on the induction of chromosome aberrations was evaluated. Blood samples collected from healthy human donors were exposed to PAA-coated and non-coated ION, at different concentrations, for 48h. The obtained results showed that, for all culture conditions, the tested ION are not genotoxic and do not influence the cell cycle arrest. Their possible cumulative effect with the iron-dependent genotoxic agent BLM was also evaluated. Blood samples collected from healthy human donors were exposed to ION, at different concentrations, for 48h, in the presence of a pre-determined toxic concentration of BLM. The obtained results showed that, for all culture conditions, the tested ION do not potentiate the clastogenic effects of BLM.