RESUMO
PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Estudos Prospectivos , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos Alquilantes/efeitos adversosRESUMO
PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/mortalidade , Idoso , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Temozolomida/uso terapêutico , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Fatores Etários , Terapia Combinada , Resultado do Tratamento , Gerenciamento ClínicoRESUMO
The development of packaging materials with new functionalities and lower environmental impact is now an urgent need of our society. On one hand, the shelf-life extension of packaged products can be an answer to the exponential increase of worldwide demand for food. On the other hand, uncertainty of crude oil prices and reserves has imposed the necessity to find raw materials to replace oil-derived polymers. Additionally, consumers' awareness toward environmental issues increasingly pushes industries to look with renewed interest to "green" solutions. In response to these issues, numerous polymers have been exploited to develop biodegradable food packaging materials. Although the use of biopolymers has been limited due to their poor mechanical and barrier properties, these can be enhanced by adding reinforcing nanosized components to form nanocomposites. Cellulose is probably the most used and well-known renewable and sustainable raw material. The mechanical properties, reinforcing capabilities, abundance, low density, and biodegradability of nanosized cellulose make it an ideal candidate for polymer nanocomposites processing. Here we review the potential applications of cellulose based nanocomposites in food packaging materials, highlighting the several types of biopolymers with nanocellulose fillers that have been used to form bio-nanocomposite materials. The trends in nanocellulose packaging applications are also addressed.
Assuntos
Celulose/química , Embalagem de Alimentos , Nanocompostos/química , Biodegradação Ambiental , Biopolímeros/química , Fenômenos QuímicosRESUMO
BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Razão de Chances , Prognóstico , Estudos Prospectivos , Sarcoma de Ewing/mortalidade , Espanha , Taxa de Sobrevida , Taxoides/administração & dosagem , GencitabinaRESUMO
BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Recidiva , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Adulto Jovem , GencitabinaRESUMO
INTRODUCTION: Clinicians still face significant challenge in predicting intra-abdominal injuries in patients admitted to an emergency department for blunt abdominal trauma. This study was thus designed to investigate the value of dipstick urinalysis in patients with blunt abdominal trauma. METHODS: We performed a retrospective, multicenter, cohort study involving patients admitted to the emergency department for abdominal traumas, examined by means of urinary dipstick and abdominal CT scan. The primary endpoint was the correlation between microscopic hematuria detected via dipstick urinalysis (defined by the presence of blood on the dipstick urinalysis but without gross hematuria) and abdominal injury, as evidenced on CT scan. RESULTS: Of the 100 included patients, 56 experienced microscopic hematuria, 17 gross hematuria, and 44 no hematuria. Patients with abdominal injury were more likely to present with hypovolemic shock (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 2.7-26), abdominal wall hematoma (OR: 3.1; 95% CI: 1.2-7.9), abdominal defense (OR: 5.2; 95% CI: 1.8-14.5), or anemia (OR: 3.6; 95% CI: 1.2-10.3). Moreover, dipstick urinalysis was less likely to predict injury, with just 72.2% sensitivity (95% CI: 54.8-85.8), 53.1% specificity (95% CI: 40.2-65.7), and positive and negative predictive values of 46.4% (95% CI: 33.0-60.3) and 77.3% (95% CI: 62.2-88.5), respectively. CONCLUSION: Dipstick urinalysis was neither adequately specific nor sensitive for predicting abdominal injury and should thus not be used as a key assessment component in patients suffering from blunt abdominal trauma, with physical exam and vital sign assessment the preferred choice.
Assuntos
Traumatismos Abdominais/urina , Hematúria/diagnóstico , Sistema Urinário/lesões , Ferimentos não Penetrantes/urina , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico por imagem , Acidentes por Quedas , Acidentes de Trânsito , Adulto , Idoso , Anemia/etiologia , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Choque/etiologia , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagemRESUMO
The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither test can rule out TB; however, a positive test usually triggers preventive treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results and it is unclear how discordant results should be interpreted in terms of TB risk and preventive treatment. To understand the immune processes underlying concordant or discordant TST and QFTGIT results, we analyzed immune responses in children from Palamaner Taluk in India (a TB-endemic region with routine neonatal BCG vaccination) who were referred to a TB case verification ward on suspicion of TB. Two hundred and ten children aged <3 years were classified according to their TST and QFTGIT results, and their immune responses analyzed by dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-γ are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma-induced protein 10 (IP-10) (P=0.001) are differentially expressed between the TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in concordant positive children and results were consistent with elevated expression of genes associated with inflammatory responses. Children with discordant test results displayed a mixed profile with activation of both pro- and anti-inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct but overlapping aspects of host immunity.
Assuntos
Teste Tuberculínico/normas , Tuberculose/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Proteínas de Transporte/sangue , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Interferon gama/sangue , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase Multiplex/normas , Estudos Prospectivos , Receptores de Formil Peptídeo/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Sensibilidade e Especificidade , Tuberculose/imunologia , Regulação para CimaRESUMO
The aim was to investigate the effects of the intra-session exercise order during water-based concurrent training on the neuromuscular adaptations in young women. 26 women (25.1±2.9 years) were placed into 2 groups: resistance prior to (RA) or after (AR) aerobic training. Subjects performed resistance (sets at maximal effort) and aerobic training (exercises at heart rate corresponding to the second ventilatory threshold) twice a week over 12 weeks, performing both exercise types in the same training session. Upper (elbow flexion) and lower-body (knee extension) one-repetition maximum test (1RM) and peak torque (PT) were evaluated. The muscle thickness (MT) of upper (sum of MT of biceps brachii and brachialis) and lower-body (sum of MT of vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris) was determined by ultrasonography. Moreover, the maximal electromyographic activity (EMG) of upper (biceps brachii) and lower-body (sum of EMG of vastus lateralis and rectus femoris) was measured. Both RA and AR groups increased the upper and lower-body 1RM and PT, while the lower-body 1RM increases observed in the RA was greater than AR (43.58±14.00 vs. 27.01±18.05%). RA and AR showed MT increases in all muscles evaluated, while the lower-body MT increases observed in the RA were also greater than AR (10.24±3.11 vs. 5.76±1.88%). There were increases in the maximal EMG of upper and lower-body in both RA and AR, with no differences between groups. Performing resistance prior to aerobic exercise during water-based concurrent training seems to optimize the lower-body strength and hypertrophy.
Assuntos
Adaptação Fisiológica/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Água , Adulto , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Contração Isométrica/fisiologia , Perna (Membro)/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/crescimento & desenvolvimento , Consumo de Oxigênio , Treinamento Resistido/métodos , Torque , UltrassonografiaRESUMO
Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children was examined by dual-color Reverse-Transcriptase Multiple Ligation-dependent Probe-Amplification for the expression of 45 genes and a Bio-Plex assay for the expression of cytokines/chemokines in QuantiFERON supernatants. The study shows that transcription of SEC14L1, GUSB, BPI, CCR7 and TGFß-1 (all P ≤ 0.05) was downregulated in TB disease compared with uninfected controls, while transcription of RAB33A was downregulated in TB disease compared with both latent TB (P < 0.05) and controls (P < 0.01). The transcription of CD4, TGFß-1 (P < 0.01) and the expression of IL-2 (P < 0.01) and IL-13 (P < 0.05) was upregulated in latent TB compared with that in controls. Using the Least Absolute Shrinkage and Selection Operator (lasso) model, RAB33A alone discriminated between TB disease and latent TB (area under the curve (AUC) 77.5%), whereas a combination of RAB33A, CXCL10, SEC14L1, FOXP3 and TNFRSF1A was effective in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFß-1 and IL-2, IL-13 may identify latent TB in children.
Assuntos
Antígenos CD4/metabolismo , Interleucina-13/metabolismo , Interleucina-2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tuberculose/diagnóstico , Proteínas rab de Ligação ao GTP/metabolismo , Vacina BCG/uso terapêutico , Biomarcadores/metabolismo , Antígenos CD4/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Índia , Lactente , Recém-Nascido , Interleucina-13/genética , Interleucina-2/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Crescimento Transformador beta1/genética , Tuberculose/metabolismo , Tuberculose/prevenção & controle , Proteínas rab de Ligação ao GTP/genéticaRESUMO
This study investigated the chronology of neural and morphological adaptations to knee extensor eccentric training and their contribution to strength gains in isometric, concentric and eccentric muscle actions. 20 male healthy subjects performed a 12-week eccentric training program on an isokinetic dynamometer, and neuromuscular evaluations of knee extensors were performed every 4 weeks. After 12 training weeks, significant increases were observed for: isometric (24%), concentric (15%) and eccentric (29%) torques; isometric (29%) and eccentric (33%) electromyographic activity; muscle thickness (10%) and anatomical cross-sectional area (19%). Eccentric and isometric torques increased progressively until the end of the program. Concentric torque and muscle mass parameters increased until the eighth training week, but did not change from this point to the twelfth training week. Eccentric and isometric activation increased at 4 and 8 training weeks, respectively, while no change was found in concentric activation. These results suggest that: 1) the relative increment in concentric strength was minor and does not relate to neural effects; 2) eccentric and isometric strength gains up to 8 training weeks are explained by the increased neural activation and muscle mass, whereas the increments in the last 4 training weeks seem to be associated with other mechanisms.
Assuntos
Adaptação Fisiológica , Joelho/fisiologia , Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Quadríceps/fisiologia , Treinamento Resistido/métodos , Adulto , Eletromiografia , Teste de Esforço , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Dinamômetro de Força Muscular , Músculo Quadríceps/anatomia & histologia , Músculo Quadríceps/diagnóstico por imagem , Fatores de Tempo , Torque , UltrassonografiaRESUMO
INTRODUCTION: Dysphagia is a common post-stroke complication, which may result in serious pulmonary sequelae. Early detection of dysphagia and aspiration risk can reduce morbidity, mortality and length of hospitalization. OBJECTIVES: This study aims to identify association between dysphagia and acute cerebrovascular disease, and evaluate the prevalence and impact of pulmonary complications on readmissions and mortality. MATERIAL AND METHODS: Retrospective observational study based on 250 clinical records of patients with acute cerebrovascular disease: clinical history, neurological examination, imaging and Gugging Swallowing Screen in the first 48h. Patients were followed for 3 months via medical records to estimate 3-month mortality and readmissions. RESULTS: Out of 250 clinical records analyzed, 102 (40.8%) were evaluated for dysphagia. The prevalence of dysphagia was 32.4%. The risk was higher in older patients (p<0.001), in severe stroke (p<0.001) and in the hemorrhagic subtype (p=0.008). An association was found with dysarthria and aphasia (p=0.003; p=0.017). Respiratory tract infections occurred in 14.4% of all patients (GUSS group 11.8% versus no GUSS group 16.2%), and in 75% of those with severe dysphagia (p<0.001). Mortality at 3 months was 24.2% in dysphagic patients, especially high in the severe dysphagia group (75%, p<0.001). CONCLUSIONS: The type of cerebrovascular disease, NIHSS and GCS scores, age, dysarthria, and aphasia were significant associated factors to dysphagia. The prevalence of respiratory tract infections was higher in patients with no GUSS record, and no statistical significance was observed in related readmissions. Mortality at 3 months was superior in the severe dysphagia group.
Assuntos
Afasia , Transtornos de Deglutição , Infecções Respiratórias , Acidente Vascular Cerebral , Humanos , Idoso , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Disartria/complicações , Acidente Vascular Cerebral/complicações , Afasia/etiologia , Afasia/complicações , Infecções Respiratórias/complicaçõesRESUMO
Quadriceps muscle weakness is frequently associated with knee injuries in sports. The influence of quadriceps weakness on knee joint homeostasis remains undefined. We hypothesized that quadriceps weakness will lead to tissue-specific alterations in the cell metabolism of tissues of the knee. Quadriceps weakness was induced with repetitive injections of Botulinum toxin A in six 1-year-old New Zealand White rabbits for 6 months. Five additional animals served as controls with injections of saline/dextrose. Muscle weakness was assessed by muscle wet mass, isometric knee extensor torque, and histological morphology analysis. Cell metabolism was assessed for patellar tendon, medial and lateral collateral ligament, and medial and lateral meniscus by measuring the total RNA levels and specific mRNA levels for collagen I, collagen III, MMP-1, MMP-3, MMP-13, TGF-ß, biglycan, IL-1, and bFGF by reverse transcription and polymerase chain reaction. While the total RNA levels did not change, tissue-specific mRNA levels were lower for relevant anabolic and catabolic molecules, indicating potential changes in tissue mechanical set points. Quadriceps weakness may lead to adaptations in knee joint tissue cell metabolism by altering a subset of anabolic and catabolic mRNA levels corresponding to a new functional and metabolic set point for the knee that may contribute to the high injury rate of athletes with muscle weakness.
Assuntos
Adaptação Fisiológica , Ligamentos Colaterais/metabolismo , Articulação do Joelho/metabolismo , Debilidade Muscular/patologia , Músculo Quadríceps/patologia , RNA Mensageiro/metabolismo , Animais , Biglicano/genética , Toxinas Botulínicas Tipo A , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Modelos Animais de Doenças , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Interleucina-1/genética , Articulação do Joelho/fisiopatologia , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Ligamento Colateral Médio do Joelho/metabolismo , Meniscos Tibiais/metabolismo , Debilidade Muscular/induzido quimicamente , Debilidade Muscular/fisiopatologia , Tamanho do Órgão , Ligamento Patelar/metabolismo , Músculo Quadríceps/fisiopatologia , Coelhos , Fator de Crescimento Transformador beta/genéticaRESUMO
Responses of leaf water relations and photosynthesis to summer drought and autumn rewetting were studied in two evergreen Mediterranean oak species, Quercus ilex spp. rotundifolia and Quercus suber. The predawn leaf water potential (Ψ(lPD)), stomatal conductance (gs) and photosynthetic rate (A) at ambient conditions were measured seasonally over a 3-year period. We also measured the photosynthetic response to light and to intercellular CO2 (A/PPFD and A/C(i) response curves) under water stress (summer) and after recovery due to autumn rainfall. Photosynthetic parameters, Vc(max), J(max) and triose phosphate utilization (TPU) rate, were estimated using the Farquhar model. RuBisCo activity, leaf chlorophyll, leaf nitrogen concentration and leaf carbohydrate concentration were also measured. All measurements were performed in the spring leaves of the current year. In both species, the predawn leaf water potential, stomatal conductance and photosynthetic rate peaked in spring, progressively declined throughout the summer and recovered upon autumn rainfall. During the drought period, Q. ilex maintained a higher predawn leaf water potential and stomatal conductance than Q. suber. During this period, we found that photosynthesis was not only limited by stomatal closure, but was also downregulated as a consequence of a decrease in the maximum carboxylation rate (Vc(max)) and the light-saturated rate of photosynthetic electron transport (J(max)) in both species. The Vc(max) and J(max) increased after the first autumnal rains and this increase was related to RuBisCo activity, leaf nitrogen concentration and chlorophyll concentration. In addition, an increase in the TPU rate and in soluble leaf sugar concentration was observed in this period. The results obtained indicate a high resilience of the photosynthetic apparatus to summer drought as well as good recovery in the following autumn rains of these evergreen oak species.
Assuntos
Secas , Fotossíntese/fisiologia , Quercus/classificação , Quercus/fisiologia , Estações do Ano , Ecossistema , Região do Mediterrâneo , Folhas de Planta , Chuva , Especificidade da Espécie , Temperatura , Fatores de Tempo , Água/metabolismoRESUMO
This study investigated the effects of pedal frequency on the slow component of pulmonary oxygen uptake ( V O(2)) kinetics during heavy exercise at the same relative intensity. We hypothesized that higher pedal frequency (expected to enhance fast-twitch muscle fiber recruitment) would be associated with greater slow component amplitude (A' (s)), surface electromyography (normalized root mean square; RMS) and blood lactate concentration ([lactate]). Eight subjects performed square-wave transitions to heavy exercise at 35 and 115 rpm. Furthermore, alternated cadences square-wave transitions (35-115 rpm) were performed to examine the potential effects of additional fast-twitch muscle fiber recruitment on the slow component. Significance was accepted when P<0.05. The A' (s) was greater at higher cadences (0.58+/-0.08 and 0.70+/-0.09 L.min (-1) at 115 and 35-115 rpm, respectively) than at 35 rpm (0.35+/-0.04 L.min (-1)). Greater EMG increase over time (DeltaRMS ((10-3 min))) and [lactate] were observed at 115 and 35-115 rpm compared with 35 rpm. There was a significant correlation between A' (s) and overall DeltaRMS ((10-3 min)) for all pedal frequencies combined (r=0.63; P=0.001). Pedal frequency had no effect on time constants or time delays. These findings are consistent with the concept that progressive recruitment of muscle fibers is associated with the V O(2) slow component.
Assuntos
Ciclismo/fisiologia , Teste de Esforço/métodos , Consumo de Oxigênio , Adulto , Eletromiografia , Humanos , Masculino , Fibras Musculares de Contração Rápida/metabolismo , Músculo Esquelético/metabolismo , Fatores de TempoRESUMO
OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of fragility fractures. In RA patients, the direct effect of inflammation on bone is difficult to study because their skeleton is also affected by medication with corticosteroids and other drugs as well as aging and menopause, which contribute to bone fragility. This study used an animal model of chronic arthritis to evaluate the direct impact of chronic inflammation on biomechanical properties and structure of bone. METHODS: In the SKG mouse chronic arthritis model three point bending tests were performed on femoral bones and compression tests on vertebral bodies. Collagen structure was analysed using second-harmonic generation (SHG) imaging with a two-photon microscope, ultramorphology by scanning electron microscopy (SEM) coupled with energy dispersive x-ray spectroscopy (EDS) and bone density using water pycnometer. RESULTS: Arthritic bones had poor biomechanical quality compared to control bones. SHG, SEM and pycnometry disclosed variable signs of impaired collagen organization, poor trabecular architecture and low bone density. CONCLUSION: Present data demonstrate for the first time that chronic inflammation per se, without confounding influence of drugs and aging, leads to impairment of bone biomechanics in terms of stiffness, ductility and ultimate strength (fracture).
Assuntos
Artrite/patologia , Artrite/fisiopatologia , Fêmur/patologia , Fêmur/fisiopatologia , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , Animais , Artrite/metabolismo , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Doença Crônica , Colágeno/metabolismo , Colágeno/ultraestrutura , Modelos Animais de Doenças , Feminino , Fêmur/metabolismo , Vértebras Lombares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Microscopia Eletrônica de Varredura , Espectrometria por Raios XRESUMO
BACKGROUND: Prisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. METHODS: We included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. RESULTS: 602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). CONCLUSION: In HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.
Assuntos
Antivirais/administração & dosagem , Infecções por HIV/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Prisioneiros , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Masculino , Prisões , Recidiva , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Resposta Viral SustentadaRESUMO
BACKGROUND: While yoga is thought to reduce the risk of chronic non-communicable diseases such as diabetes, there are no studies on insulin sensitivity in long term practitioners of yoga. We assessed insulin sensitivity and cardiac autonomic function in long term practitioners of yoga. METHODS: Fifteen healthy, young, male practitioners of yoga were compared with 15 young, healthy males who did not practice yoga matched for body-mass index. Fasting insulin sensitivity was measured in the fasting state by the hyperinsulinaemic-euglycaemic clamp. RESULTS: There were no significant differences between the groups in their anthropometry or body composition. However, the fasting plasma insulin was significantly lower in the yoga group. The yoga group was also more insulin sensitive (yoga 7.82 [2.29] v. control 4.86 [11.97] (mg/[kg.min])/(microU/ml), p < 0.001). While the body weight and waist circumference were negatively correlated with glucose disposal rate in the controls, there were no similar correlations in the yoga group. The yoga group had significantly higher low-frequency power and lower normalized high-frequency power. CONCLUSION: Long term yoga practice (for 1 year or more) is associated with increased insulin sensitivity and attenuates the negative relationship between body weight or waist circumference and insulin sensitivity.
Assuntos
Sistema Nervoso Autônomo , Coração , Resistência à Insulina , Insulina/sangue , Yoga , Adulto , Análise de Variância , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Jejum , Técnica Clamp de Glucose , Humanos , MasculinoRESUMO
Covid-19 has devastated human lives and stretched the limits of the medical profession and health systems. Using the mixed methods of online survey and online focus group discussions, we assessed how medical students and interns of two medical colleges in South India viewed the profession they had chosen. Of the 900 participants, 571(63.4%) had a positive perception of the medical profession, 77(8.6%) a negative perception and 252(28%) were undecided. The year of study in medical school was significantly associated with their perception of the medical profession, with interns more likely to have a negative perception (p<0.001). An overwhelming 823(91.4%) participants remained confident of their career choice, but a higher proportion of interns were less confident or regretful about their choice of profession compared to first to fourth year students (p<0.001). Most participants experienced moral distress; they acknowledged a duty to care but were troubled by personal risk, inadequate protection, and limited resources. Gaps were identified in medical and ethics training particularly regarding uncertainties and coping with deficiencies of the health system as encountered in the pandemic. The essential role played by doctors with its required competence, care and ethics cannot be assumed or expected without investment in the making of the future doctor through more socially embedded medical education imparting the skills of understanding the public, responding to them and being the advocate for their equitable and optimal care. An ethics of responsiveness emerges as important for healthcare, also for medical education in preparation for future health crises.
RESUMO
Despite the wide and growing use of microsurgery, its application in primary burn reconstruction is not very frequent as it faces a number of additional challenges in this setting. A retrospective analysis of the clinical records of all patients submitted to microvascular free tissue transfer for primary burn reconstruction over an 8-year period (from January 2009 to December 2016) was performed. An evaluation of the indications, timing, principles of flap selection, complications and outcomes of free tissue transfer in primary burn reconstruction was made. Fourteen patients required 18 microsurgical flaps for acute soft tissue reconstruction (1.1% of all patients admitted). 64.3% of the patients were male. The mean age was 59.64 years, and mean TBSA was 10.5%. The majority of the injuries were caused by flames (71.4%), followed by electrical contact (21.4%). The primary indication for microsurgical reconstruction was tissue deficit with exposure of tendons, nerves, vessels, bone and/or joints after debridement. The procedure was more often performed in the early period after injury (between the 5th and 22nd day). The most frequently used flaps were the Latissimus dorsi and the anterolateral thigh flap. Major complications included 2 total flap failures (11.1%) and a partial flap failure that required reconstruction with another free flap. Microsurgical free flaps have a valuable role in primary burn reconstruction. Despite the reported higher complication rate in this specific clinical scenario, their use may reduce the total number of surgeries needed to achieve wound closure.
Bien que de plus en plus utilisée, la microchirurgie est rarement utilisée dans la prise en charge initiale des brûlés, et doit faire face à plusieurs difficultés supplémentaires dans cette indication. Nous avons effectué une analyse rétrospective des dossiers de tous les patients brûlés entre janvier 2009 et décembre 2016 ayant bénéficié au stade d'un lambeau libre (LL). Nous avons évalué l'indication, le délai, la sélection du site donneur, les complications et l'évolution du lambeau. Quatorze patients (1,1% du total) dont 64,5% d'hommes ont bénéficié de 18 LL. L'âge moyen était de 59,64 ans, la surface brûlée de 10,5%. La majorité des brûlures (71,4%) étaient dues à une flamme, 21,4% à l'électricité. L'indication principale était l'exposition ostéo-articulaire ou d'éléments nobles (tendons, nerfs, vaisseaux) après excision. La réalisation du LL était précoce (J5-J22). Les sites donneurs étaient Latissimus dorsi et la région antéro-latérale de cuisse. Deux lambeaux ont totalement nécrosé, un partiellement, ce qui a nécessité la réalisation d'un second LL. Les LL ont une place dans la prise en charge initiale des brûlés. Bien de grevés d'un taux de complications plus élevé dans cette indication, ils peuvent permettre de diminuer le nombre d'interventions nécessaires à la cicatrisation.