RESUMO
This study investigates agro-industrial by-products as sources of bioactive compounds, particularly focusing on phenolic compounds known for their antioxidant properties. With growing interest in natural alternatives to synthetic antioxidants due to safety concerns, this study highlights the health benefits of plant-derived phenolic compounds in food preservation and healthcare products. Traditional and advanced analytical techniques were used to obtain phytochemical profiles of various residue extracts, including espresso (SCG) and cold-brew spent coffee grounds (CBCG), pineapple peel (PP), beetroot pomace (BP), apple pomace (AP), black carrot pomace (BCP), and garlic peel (GP). Assessments of total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity (AC) supported their revalorization. CBCG showed the highest TPC, TFC, and AC. TPC content in by-products decreased in the order CBCG > SCG > GP > BCP > PP > AP > BP, with a similar trend for TFC and AC. Phytochemical profiling via FI-ESI-FTICR-MS enabled the preliminary putative identification of a range of compounds, with polyphenols and terpenes being the most abundant. Univariate and multivariate analyses revealed key patterns among samples. Strong positive correlations (Pearson's R > 0.8) indicated significant contribution of polyphenols to antioxidant capacities. These findings highlight the potential of agro-industrial residues as natural antioxidants, advocating for their sustainable utilization.
RESUMO
BACKGROUND: Nutritional strategies with iron supplementation have been shown to be effective in preventing the decline of blood biochemical parameters and sports performance. The aim of the study was to describe biochemical iron metabolism parameters in association with iron supplementation and HFE and AMPD1 polymorphisms in a Union Cycliste Internationale (UCI) World Tour cycling team to evaluate performance during a whole season METHODS: Twenty-eight professional men cyclists took part in this longitudinal observational pilot study. AMPD1 c.34â¯C>T (rs17602729) and HFE c.187â¯C>G (rs1799945) polymorphisms were genotyped using Single Nucleotide Primer Extension (SNPE). All the professional cyclists took oral iron supplementation throughout the season. Four complete blood analyses were carried out corresponding to UCI controls in January (1st), April (2nd), June (3rd) and October (4th). Data on participation in three-week Grand Tours, kms of competition and wins were analyzed. RESULTS: In performance, especially in wins, there was a significant effect in HFE on biochemical hemoglobin (F = 4.255; p = 0.021) and biochemical hematocrit (F = 5.335; p = 0.009) and a hematocrit biochemical × genotype interaction (F = 3.418; p = 0.041), with higher values in professional cyclist with GC genotype. In AMPD1 there were significant effects in the biochemical iron x genotype interaction in three-week Grand Tours (F = 3.874; p = 0.029) and wins (F = 3.930; p = 0.028) CONCLUSIONS: Blood biochemical iron metabolism parameters could be related to performance in the season due to increasing hemoglobin and hematocrit concentration under iron supplementation, associated with winning in the professional cyclists with GC genotype of the HFE polymorphism.
Assuntos
AMP Desaminase , Suplementos Nutricionais , Proteína da Hemocromatose , Ferro , Humanos , Masculino , Proteína da Hemocromatose/genética , Projetos Piloto , Ferro/metabolismo , Ferro/sangue , Adulto , AMP Desaminase/genética , Ciclismo , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem , GenótipoRESUMO
PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.
Assuntos
Compostos de Anilina , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Mutação , Pirazinas , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Pirazinas/uso terapêutico , Adulto , Compostos de Anilina/uso terapêutico , Idoso , Sequências de Repetição em Tandem , Adulto Jovem , Neoplasia Residual , Inibidores de Proteínas Quinases/uso terapêutico , Quimioterapia de Manutenção , Duplicação GênicaRESUMO
OBJECTIVE: This trial examined the effects of proximal/distal mediators and moderators of an Active Music Engagement (AME) intervention on young child/parent distress, quality of life, and family function outcomes. METHODS: Child/parent dyads (n = 125) were randomized to AME or Audio-storybooks attention control condition. Each group received 3 sessions with a credentialed music therapist for 3 consecutive days with data collection at baseline, post-intervention (T2), and 30-days later (T3). Potential proximal mediators included within session child and parent engagement. Potential distal mediators included changes in perceived family normalcy, parent self-efficacy, and independent use of play materials. Potential moderators included parent/child distress with prior hospitalizations, parent traumatic stress screener (PCL-6), and child age. Outcomes included child emotional distress and quality of life; parent emotion, traumatic stress symptoms (IES-R), well-being; and family function. Mediation effects were estimated using ANCOVA, with indirect effects estimated using the percentile bootstrap approach. Moderation effects were tested by including appropriate interaction terms in models. RESULTS: No significant mediation effects were observed. Child distress with prior hospitalizations moderated AME effects for IES-R intrusion subscale scores at T2 (P = .01) and avoidance subscale scores at T3 (P = .007). Traumatic stress screener scores (PCL-6) moderated intervention effects for IES-R hyperarousal subscale scores at T2 (P = .01). There were no moderation effects for child age. CONCLUSIONS: AME is a promising intervention for mitigating traumatic stress symptoms and supporting well-being in parents of children with cancer, particularly for parents who screen high for traumatic stress and whose children are more highly distressed with hospitalization.
Assuntos
Musicoterapia , Neoplasias , Pais , Transtornos de Estresse Traumático , Criança , Pré-Escolar , Humanos , Emoções , Música , Neoplasias/psicologia , Pais/psicologia , Qualidade de Vida , Transtornos de Estresse Traumático/etiologia , Transtornos de Estresse Traumático/psicologia , Transtornos de Estresse Traumático/terapiaRESUMO
BACKGROUND AND OBJECTIVES: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5+ ). PATIENTS AND METHODS: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5+ . Demographic data, laboratory data, and clinical manifestations were collected. RESULTS: Anti-MDA5+ DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5+ patients (p <0.001), being a diagnostic marker of anti-MDA5+ (OR, 12.355; 95% CI 2.850-79.263; p = 0.012 and OR, 7.447; 95% CI 2.103-46.718; p = 0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5+ patients, because in our cohort, up to 97% of the anti-MDA5+ patients had ulcers. CONCLUSIONS: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor.
Assuntos
Dermatomiosite , Humanos , Estudos Retrospectivos , Helicase IFIH1 Induzida por Interferon , Úlcera , Estudos Transversais , Autoanticorpos , PrognósticoRESUMO
PURPOSE: The effect of caffeine to enhance fat utilisation as fuel for submaximal aerobic exercise is well established. However, it is unknown whether this effect is dose dependent. The aim of this study was to investigate the effect of 3 and 6 mg of caffeine per kg of body mass (mg/kg) on whole-body substrate oxidation during an incremental cycling exercise test. METHODS: In a double-blind, randomised, and counterbalanced experiment, 18 recreationally active males (maximal oxygen uptake [VO2max] = 56.7 ± 8.2 mL/kg/min) performed three experimental trials after ingesting either 3 mg/kg of caffeine, 6 mg/kg of caffeine or a placebo (cellulose). The trials consisted of an incremental exercise test on a cycle ergometer with 3-min stages at workloads from 30 to 80% of VO2max. Energy expenditure, fat oxidation rate, and carbohydrate oxidation rate were continuously measured by indirect calorimetry. RESULTS: During exercise, there was significant effect of substance (F = 7.969; P = 0.004) on fat oxidation rate. In comparison to the placebo, the rate of fat oxidation was higher with 3 mg/kg of caffeine at 30, 40, 50 and 70% of VO2max [all P < 0.050, effect sizes (ES) from 0.38 to 0.50] and with 6 mg/kg of caffeine at 30, 40, 50, 60 and 70% of VO2max (all P < 0.050, ES from 0.28 to 0.76). Both 3 mg/kg (0.40 ± 0.21 g/min, P = 0.021, ES = 0.57) and 6 mg/kg of caffeine (0.40 ± 0.17 g/min P = 0.001, ES = 0.60) increased the maximal rate of fat oxidation during exercise over the placebo (0.31 ± 0.15 g/min). None of the caffeine doses produced any significant effect on energy expenditure or heart rate during exercise, while both caffeine doses reduced perceived fatigue at 80% of VO2max (all P < 0.050, ES from 0.71 to 1.48). CONCLUSION: The effect of caffeine to enhance fat oxidation during submaximal aerobic exercise is of similar magnitude with 3 and 6 mg of caffeine per kg of body mass. Thus, a dose of 3 mg of caffeine per kg of body mass would be sufficient to enhance fat utilisation as fuel during submaximal exercise.
Assuntos
Cafeína , Exercício Físico , Masculino , Humanos , Cafeína/farmacologia , Exercício Físico/fisiologia , Oxirredução , Metabolismo Energético , Teste de Esforço , Método Duplo-Cego , Consumo de Oxigênio/fisiologiaRESUMO
BACKGROUND: Lateral epicondylitis is common in workers who perform repetitive movements of the entire upper limb. Approximately 85%-90% of patients respond satisfactorily to conservative treatment, but in resistant patients, surgical treatment is considered. Classic open surgery is successful in between 70% and 97% of patients, similarly to more modern techniques such as arthroscopy. We sought to demonstrate the superiority of the Wolff technique in terms of clinical results. The goals of this study were to compare the functional and pain outcomes of arthroscopic surgery with open surgery using fasciotomy via the Wolff technique in the treatment of lateral epicondylitis. METHODS: This was a retrospective study of 47 working-age patients with resistant lateral epicondylitis: 27 underwent arthroscopic surgery and 20 underwent open surgery. Visual analog scale scores for pain and function, as well as the QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score, Mayo Elbow Performance Score, and Broberg and Morrey Rating System score, were collected preoperatively and postoperatively; return to patients' previous work and surgical time were also recorded. RESULTS: No statistically significant differences were observed between the groups in the reduction in the visual analog scale score (5.26 in arthroscopy group vs. 5.75 in fasciotomy group, P = .5), QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score (19 vs. 19.4, P = .9), Mayo Elbow Performance Score (82 vs. 81.5, P = .8), or Broberg and Morrey Rating System score (81.9 vs. 82.6, P = .9). The differences in terms of time off were also not statistically significant. The period of work leave corresponded, on average, to 83.78 days in the arthroscopy group and 89.95 days in the Wolff group. The mean surgical time was 44.2 minutes in the group undergoing arthroscopic intervention and 27.5 minutes in the fasciotomy group, showing a statistically significant difference (P < .001). CONCLUSIONS: Arthroscopic surgery and open surgery provide similar functional results and pain reduction in the treatment of lateral epicondylitis.
Assuntos
Cotovelo de Tenista , Artroscopia/métodos , Cotovelo , Seguimentos , Humanos , Dor/etiologia , Estudos Retrospectivos , Cotovelo de Tenista/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Stoma site incisional hernias after ileostomy closure are complex hernias that can be associated with abdominal pain, discomfort, and a diminished quality of life. The aim of this study was to determine the incidence of incisional hernia (IH) following temporary ileostomy reversal in patients undergoing colorectal surgery, and the risk factors associated with its development. METHODS: This was a prospective, single-centre, cohort study of patients undergoing ileostomy reversal between January 2010 and December 2016. Comorbidities, operative characteristics, comparison between early and late ileostomy closure and postoperative complications were analysed. RESULTS: A total of 202 consecutive patients were prospectively evaluated (median follow-up 46 months; range: 12-109). Stoma site incisional hernia occurred in 23% of patients (n = 47), diagnosed by physical examination or imaging tests. The reasons for the primary surgery were colorectal cancer (n = 141, 69.8%), inflammatory bowel disease (n = 14, 6.9%), emergency surgery (n = 35, 17.3%), and other conditions (n = 12, 5.9%). Secondary outcomes: a statistically significant risk factors for developing an IH was obesity (higher BMI) (OR 1.15, 95% CI: 1.05-1.26) p = .003). CONCLUSIONS: 23% of patients developed surgical site IH, a higher BMI being the only risk factor found to be statistically significant in the development of an incisional hernia.
Assuntos
Cirurgia Colorretal , Hérnia Incisional , Estudos de Coortes , Humanos , Ileostomia/efeitos adversos , Incidência , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Microsatellite instability occurs due to a series of mutations in the DNA pairing error repair (Mismatch repair; MMR) genes, which can affect germ cells as occurs in Lynch syndrome, whose patients are at high risk of developing multiple cancers. The loss of MMR protein is commonly determined by immunohistochemical studies. Although the relation between microsatellite instability and urothelial carcinomas has been widely studied, its evaluation is not currently performed in the analysis of urothelial carcinomas. METHODS: In this study, the microsatellite status of 139 urothelial carcinomas was analyzed and their clinicopathological characteristics were evaluated. We identified that 10.3% (13 patients) of urothelial carcinomas had loss of MMR protein expression (9 MLH1; 5 MSH2; 2 PMS2; 2 PSH6; n = 139). RESULTS: Results suggest that these tumors occur more frequently in males, are more frequently located in the bladder or ureters, and present a high tumor grade with a papillary histological pattern that does not infiltrate the lamina propria or, in the case of infiltrating tumors, that grows into perivesical tissues. CONCLUSIONS: We identified patients with the aforementioned tumor characteristics as patients with a high probability of presenting loss of MMR protein expression, and consider that only these patients should undergo further immunohistochemical and molecular techniques for proper diagnosis. Therefore, we propose that the clinicopathological characteristics found in the present study could become possible markers to determine which cases should undergo additional tests.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Enzimas Reparadoras do DNA/genética , Instabilidade de Microssatélites , Neoplasias Urológicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma/química , Carcinoma/patologia , Criança , Pré-Escolar , Enzimas Reparadoras do DNA/análise , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/análise , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/análise , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/análise , Proteína 2 Homóloga a MutS/genética , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Neoplasias Urológicas/química , Neoplasias Urológicas/patologia , Urotélio/química , Urotélio/patologia , Adulto JovemRESUMO
To determine the functional recovery, active reincorporation, and anteroposterior and rotational stability of patients undergoing anterior cruciate ligament (ACL) reconstruction using arthroscopy techniques with simple-bundle (SB) or double-bundle (DB). The following databases were searched: PubMed, Embase (Elsevier platform), the Cochrane Central Register of Controlled Trials (Wiley platform), Web of Science, and CINAHL. Level I and II studies involving anterior cruciate ligament arthroscopy were included in the search. Records were screened by title and abstract and assessed the risk of bias of selected studies. Meta-analyses using RevMan 5.3 software were conducted on the following outcomes: knee functionality, objective measurements of knee stability, rotational knee stability and knee anterior stability, sports reincorporation, and subjective assessments. Twenty-four studies of patients undergoing ACL reconstruction were included in the qualitative and quantitative synthesis (1707 patients) for Lysholm score, Subjective International Knee Documentation Committee (IKDC) score, Tegner score, KT-1000/2000, Lachman test, Objective IKDC score, and Pivot-Shift test. A return to pre-injury level showed a significant decrease in the Lysholm score (mean difference, - 0.99; 95% CI - 1.71 to - 0.40; P = 0.007) and Tegner score (mean difference, - 0.07; 95% CI, - 0.13 to - 0.01; P = 0.02) at DB reconstruction, similar to the knee functionality outcome of the subjective IKDC score (mean difference - 1.42; 95% CI - 2.46 to - 0.38; P = 0.007). There is no clear or significant difference in clinical stability and knee function or in sports incorporation with the true difference occurring in the subjective assessment.
Assuntos
Lesões do Ligamento Cruzado Anterior/reabilitação , Reconstrução do Ligamento Cruzado Anterior/normas , Ligamento Cruzado Anterior/diagnóstico por imagem , Traumatismos do Joelho/reabilitação , Ligamento Cruzado Anterior/fisiopatologia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Artroscopia/normas , Humanos , Instabilidade Articular/fisiopatologia , Instabilidade Articular/reabilitação , Traumatismos do Joelho/terapia , Articulação do Joelho/fisiopatologia , Recuperação de Função Fisiológica/fisiologiaRESUMO
OBJECTIVE: Evaluate the association between health relate quality of life and sexual desire in postmenopausal women and the influence of demographic descriptors on sexual desire. METHODS: A observational-cross-sectional study was conducted in 521 postmenopausal women in La Zarzuela Hospital between 2018-2020. Cervantes-short form (Cervantes-SF) scale and Brief profile female sexual function (B-PFSF) scale were filled out in the consultation. High score in Cervantes-SF implies worse health-related quality of life (HR-QoL). If score is lower or equal to 20 in B-PFSF implies diagnosis of hypoactive sexual desire disorder. RESULTS: There is a positive relationship between HR-QoL measured by Cervantes-SF and sexual desire measured by B-PFSF (p < .001; correlation coefficient: .223). The mean score on Cervantes-SF was 30.8 ± 14.9 and on B-PFSF was 18.7 ± 7.4. The B-PFSF score was worse in those women using systemic or vaginal hormonal treatment versus using non-hormonal treatment (18.7 ± 7.8 or 17.2 ± 7.4 vs 19.7 ± 6.5; p = .033. Smoking (b exp: .384; p = .029) and using vaginal hormonal treatment (b exp: 1.759; p = .033) are independent factors related to sexual desire. No difference was found in the wellbeing perceived by women in the different treatments (mean of minimal clinically important difference score was 2.9 in systemic vs. 3.0 in vaginal hormonal treatment). CONCLUSIONS: Improvement on HR-QoL is related to improvement on sexual desire. Sexual desire is better in women with non-hormonal treatment than in women with systemic or vaginal hormonal treatment. The vaginal hormonal treatment and being current smoker are independent factors of low and high sexual desire, respectively.
Assuntos
Pós-Menopausa/psicologia , Sexualidade/psicologia , Estudos Transversais , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
This paper reports the results of a single case design pilot study of a music therapy intervention [the Active Music Engagement (AME)] for young children (age 3.51 to 4.53 years) undergoing hematopoietic stem cell transplantation (HCST) and their caregivers. The primary aims of the study were to determine feasibility/acceptability of the AME intervention protocol and data collection in the context of HCST. Secondary aims were to examine caregivers' perceptions of the benefit of AME and whether there were changes in child and caregiver cortisol levels relative to the AME intervention. Results indicated that the AME could be implemented in this context and that data could be collected, though the collection of salivary cortisol may constitute an additional burden for families. Nevertheless, data that were collected suggest that families derive benefit from the AME, which underscores the need for devising innovative methods to understand the neurophysiological impacts of the AME.
RESUMO
OBJECTIVE: Endoscopist-directed propofol (EDP) sedation is becoming more popular, with a reported safety and efficacy similar to anesthesiologist-administered propofol (AAP). The aim of this study is to compare the efficiency of EDP and AAP in patients of low-intermediate anesthetic risk. METHODS: A prospective cost-effectiveness comparison study was conducted. The costs of the endoscopic procedures in the EDP and AAP group were calculated using the full cost methodology after breaking down the endoscopic activity into relative value units to allocate costs in an equitable way. To determine the effectiveness, adverse events related to endoscopic sedation and the number of incomplete procedures were registered for the EDP group and compared with those published by anesthesiologists for AAP. RESULTS: A total of 1165 and 18 919 endoscopic procedures were, respectively, included in the EDP and AAP groups. The average costs of EDP vs. AAP for gastroscopy, colonoscopy and endoscopic ultrasound were &OV0556; 182.81 vs. &OV0556; 332.93, &OV0556; 297.07 vs. &OV0556; 459.76, and &OV0556; 319.92 vs. &OV0556; 485.12, respectively. No significant differences were detected regarding the rate of overall adverse events (4.43 vs. 4.46%) or serious adverse events (0 vs. 0.17%); the rate of arterial hypotension was significantly lower in the EDP group: 0.34 vs. 1.78% [odds ratio (OR), 0.19; 95% confidence interval (CI), 0.08-0.46] and the desaturation rate was significantly lower in the AAP group: 3.26 vs. 1.29% (OR, 2.58; 95% CI, 1.85-3.60). No significant differences were found in terms of incomplete examinations (0.17 vs. 0.14%). CONCLUSION: In patients with low-intermediate anesthetic risk referred for an endoscopic examination, EDP appears to be more efficient than AAP.
Assuntos
Anestésicos , Propofol , Anestesiologistas , Colonoscopia , Sedação Consciente/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Estudos ProspectivosRESUMO
Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (-163C > A, rs762551; characterized such as "fast" (AA genotype) and "slow" caffeine metabolizers (C-carriers)) and ADORA2A (1976T > C; rs5751876; characterized by "high" (TT genotype) or "low" sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d-1) ingested 3 mg·kg-1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the -163C > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8-4.3%, p = 0.001-0.022, effect size = 0.17-0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg-1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.
Assuntos
Cafeína/administração & dosagem , Citocromo P-450 CYP1A2/genética , Substâncias para Melhoria do Desempenho/administração & dosagem , Receptor A2A de Adenosina/genética , Esportes , Adolescente , Adulto , Alelos , Desempenho Atlético , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Variantes Farmacogenômicos , Adulto JovemRESUMO
PURPOSE: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. METHODS: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. RESULTS: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. CONCLUSION: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.
Assuntos
Antineoplásicos , Desenvolvimento de Medicamentos/organização & administração , Leucemia Mieloide Aguda/tratamento farmacológico , Oncologia/organização & administração , Pediatria/organização & administração , Adolescente , Idade de Início , Antineoplásicos/classificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Desenvolvimento de Medicamentos/tendências , Europa (Continente)/epidemiologia , Humanos , Agências Internacionais/organização & administração , Agências Internacionais/tendências , Cooperação Internacional , Leucemia Mieloide Aguda/epidemiologia , Oncologia/tendências , Pediatria/tendências , Análise de Sobrevida , Estados Unidos/epidemiologia , United States Food and Drug Administration/organização & administração , United States Food and Drug Administration/tendênciasRESUMO
OBJECTIVES: The aim of the study is to assess whether women who choose to use menopausal hormone therapy (MHT) have lower quality of life (QoL) than those who do not initiate it using Cervantes short form scale (C-SF), and analyze sociodemographic factors associated with lower QoL in women. STUDY DESIGN: A cross-sectional descriptive observational study was made in four hundred and eighty women with climacteric symptoms. RESULTS: Mean age was 51.1 years. Two hundred and sixty-one women (54.3 %) started MHT. The sample´s global mean in C-SF score was 51.3 ± 13.9. Women who choose to use MHT have higher score in C-SF (lower QoL) than women who reject it (58.7 ± 15.9 vs 46.7 ± 12.8; p < 0.001). We found higher score in women with early menopause (53.7 ± 15.9 vs 49.7 ± 13.1; p = 0.037); with no obesity (<30 vs >30 BMI) (52.8 ± 13.5 vs 41.0 ± 8.2; p = 0.002); with previous malignancies (56.2 ± 18.2 vs 50.2 ± 13.5; p = 0.020) and without sexual activity (58.0 ± 25.4 vs 50.4 ± 13.1; p = 0.009. No differences were found in C-SF score with respect to tobacco habits or physical activity. In the multivariate analysis, the variable independently associated to lower QoL by C-SF (high score) was to be a woman who want to initiate MHT (p = 0.004). CONCLUSIONS: Women who choose to use MHT due to menopausal symptoms have lower quality of life measured by C-SF scale. Women with early menopause, with no obesity (<30 BMI), without sexual activity and with previous malignances have lower quality of life measured by C-SF scale. Women with early menopause have more psychic symptoms like nervousness, fatigue and sleep complaints by C-SF scale than women with natural menopause.
Assuntos
Menopausa , Qualidade de Vida , Estudos Transversais , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Information about the association of energy and iron-metabolising genes with endurance performance is scarce. The objective of this investigation was to compare the frequencies of polymorphic variations of genes involved in energy generation and iron metabolism in elite endurance athletes versus nonathlete controls. Genotype frequencies in 123 male elite endurance athletes (75 professional road cyclists and 48 elite endurance runners) and 122 male nonathlete participants were compared by assessing 4 genetic polymorphisms: AMPD1 c.34C/T (rs17602729), PPARGC1A c.1444G/A (rs8192678) HFEH63D c.187C/G (rs1799945) and HFEC282Y c.845G/A (rs1800562). A weighted genotype score (w-TGS; from 0 to 100 arbitrary units (a.u.)) was calculated by assigning a corresponding weight to each polymorphism. In the nonathlete population, the mean w-TGS value was lower (39.962 ± 14.654 a.u.) than in the group of elite endurance athletes (53.344 ± 17.053 a.u). The binary logistic regression analysis showed that participants with a w-TGS > 38.975 a.u had an odds ratio of 1.481 (95% confidence interval: 1.244-1.762; p < 0.001) for achieving elite athlete status. The genotypic distribution of polymorphic variations involved in energy generation and iron metabolism was different in elite endurance athletes vs. controls. Thus, an optimal genetic profile in these genes might contribute to physical endurance in athlete status. Novelty Genetic profile in energy generation and iron-metabolising genes in elite endurance athletes is different than that of nonathletes. There is an implication of an "optimal" genetic profile in the selected genes favouring endurance sporting performance.
Assuntos
Atletas , Genótipo , Ferro/metabolismo , Resistência Física/genética , Polimorfismo Genético , AMP Desaminase/genética , Adolescente , Adulto , Estudos de Casos e Controles , Proteína da Hemocromatose/genética , Humanos , Masculino , Herança Multifatorial , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Espanha , Adulto JovemRESUMO
Chemotherapy-associated cardiotoxicity may delay or impair the ability to administer fully myeloablative chemotherapy for stem cell transplant in those with reduced left ventricular ejection fraction. Studies in adults have been inconsistent regarding the value of ejection fraction in predicting cardiotoxicity in the posttransplant period. Recent publications, however, have demonstrated successful stem cell transplantation in adults despite low ejection fractions. This case series highlights 2 pediatric patients who were successfully treated with stem cell transplantation without posttransplant cardiac complications, despite pretransplant ejection fractions of 38% and 29%.