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Topoisomerase I (TOP1) is an essential enzyme that relaxes DNA to prevent and dissipate torsional stress during transcription. However, the mechanisms underlying the regulation of TOP1 activity remain elusive. Using enhanced cross-linking and immunoprecipitation (eCLIP) and ultraviolet-cross-linked RNA immunoprecipitation followed by total RNA sequencing (UV-RIP-seq) in human colon cancer cells along with RNA electrophoretic mobility shift assays (EMSAs), biolayer interferometry (BLI), and in vitro RNA-binding assays, we identify TOP1 as an RNA-binding protein (RBP). We show that TOP1 directly binds RNA in vitro and in cells and that most RNAs bound by TOP1 are mRNAs. Using a TOP1 RNA-binding mutant and topoisomerase cleavage complex sequencing (TOP1cc-seq) to map TOP1 catalytic activity, we reveal that RNA opposes TOP1 activity as RNA polymerase II (RNAPII) commences transcription of active genes. We further demonstrate the inhibitory role of RNA in regulating TOP1 activity by employing DNA supercoiling assays and magnetic tweezers. These findings provide insight into the coordinated actions of RNA and TOP1 in regulating DNA topological stress intrinsic to RNAPII-dependent transcription.
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We identified rat hepatitis E virus (HEV) RNA in farmed pigs from Spain. Our results indicate that pigs might be susceptible to rat HEV and could serve as viral intermediaries between rodents and humans. Europe should evaluate the prevalence of rat HEV in farmed pigs to assess the risk to public health.
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Virus de la Hepatitis E , Humanos , Ratas , Animales , Porcinos , España/epidemiología , Virus de la Hepatitis E/genética , Europa (Continente) , Granjas , Salud Pública , ARNRESUMEN
Multivalent glycodendrimers are valuable tools for studying carbohydrate-protein interactions, and their scaffolds represent important components to increase specificity and affinity. Previous work by our group described the preparation of a tetravalent glucuronic acid rigid dendron that binds with good affinity to the dengue virus envelope protein (KD = 22 µM). Herein, the chemical synthesis and binding analysis of three new sets of rigid, semirigid, and flexible glucuronic acid-based dendrimers bearing different levels of multivalency and their interactions with the dengue virus envelope protein are described. The different oligoalkynyl scaffolds were coupled to glucuronic acid azides by a copper-catalyzed azide-alkyne cycloaddition reaction through optimized synthetic strategies to afford the desired glycodendrimers with good yields. Surface plasmon resonance studies have demonstrated that glycodendrimers 12b and 12c, with flexible scaffolds, give the best binding interactions with the dengue virus envelope protein (12b: KD = 0.487 µM and 12c: KD = 0.624 µM). Their binding constant values were 45 and 35 times higher than the one obtained in previous studies with a rigid tetravalent glucuronic acid dendron (KD = 22 µM), respectively. Molecular modeling studies were carried out in order to understand the difference in behavior observed for 12b and 12c. This work reports an efficient glycodendrimer chemical synthesis process that provides an appropriate scaffold that offers an easy and versatile strategy to find new active compounds against the dengue virus.
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Dendrímeros , Virus del Dengue , Dengue , Humanos , Virus del Dengue/química , Ácido Glucurónico , Proteínas del Envoltorio Viral/química , Dendrímeros/químicaRESUMEN
Citizen science is personal. Participation is contingent on the citizens' connection to a topic or to interpersonal relationships meaningful to them. But from the peer-reviewed literature, scientists appear to have an acquisitive data-centered relationship with citizens. This has spurred ethical and pragmatic criticisms of extractive relationships with citizen scientists. We suggest five practical steps to shift citizen-science research from extractive to relational, reorienting the research process and providing reciprocal benefits to researchers and citizen scientists. By virtue of their interests and experience within their local environments, citizen scientists have expertise that, if engaged, can improve research methods and product design decisions. To boost the value of scientific outputs to society and participants, citizen-science research teams should rethink how they engage and value volunteers.
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Enterocytozoon bieneusi is a microsporidia commonly found in the gastrointestinal tract of humans and a wide range of other animals, constituting a major cause of microsporidiosis in humans. Although E. bieneusi has been detected in humans, domestic, and wild animals in Portugal, and its presence in bats has been linked to zoonotic characteristics, its occurrence in bats within the country has not been reported. In this study, we investigated the presence of E. bieneusi in 380 bat fecal samples collected in mainland Portugal through a nested PCR assay targeting the internal transcribed spacer region and the flanking small and large subunits of the ribosomal RNA. Enterocytozoon bieneusi was detected in one bat sample (i.e., 0.26%; Pipistrellus pipistrellus). Additionally, another sample tested positive for Enterocytozoon sp. Phylogenetic analysis of the obtained ITS sequence of E. bieneusi revealed clustering within the potentially zoonotic Group 1. This study represents the first report of E. bieneusi in a bat from Europe. Findings presented here contribute to an enhanced understanding of E. bieneusi epidemiology.
Enterocytozoon bieneusi is the most frequent cause of microsporidiosis in humans. In this study, E. bieneusi, belonging to a potentially zoonotic Group, was detected in 0.26% bat samples from Portugal, highlighting bats' potential role in transmitting this microsporidia to humans and other animals.
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Quirópteros , Enterocytozoon , Microsporidiosis , Animales , Humanos , Enterocytozoon/genética , Genotipo , Portugal/epidemiología , Filogenia , ADN Espaciador Ribosómico/genética , Prevalencia , Microsporidiosis/epidemiología , Microsporidiosis/veterinaria , Heces , China/epidemiologíaRESUMEN
PURPOSE: Barbed sutures are tissue control devices that can reduce operating room time and costs. We analyzed the utility of barbed sutures in posterior spinal surgery in order to prove non-inferiority to conventional methods for wound closure. METHODS: A cohort of patients undergoing elective posterior spinal surgery in which barbed (prospective) versus conventional sutures (retrospective) were used was analyzed. The primary endpoint was the occurrence of wound healing complications or the need for surgical revision. Secondary endpoints included postoperative stay, readmission rate, and duration and cost of wound closure. RESULT: A total of 483 patients participated in the study, 183 in the Barbed group and 300 in the Conventional group. Wound dehiscence or seroma occurred in 3.8% and 2.7% of the Barbed and Conventional groups, respectively (p = 0.6588). Both superficial (1.6% versus 4.0%, P = 0.2378) and deep infections (2.7% versus 4.7%, p = 0.4124) occurred similarly in both groups. Overall, the rate of re-intervention due to wound healing problems was also similar (4.9% versus 5.3%, p = 0.9906), as well as, total median hospital stay, postoperative stay and 30-day re-admission rates. The average duration of wound closure (1.66 versus 4.16 min per level operated, p < 0.0001) strongly favored the Barbed group. The mean cost of wound closure per patient was higher in the Barbed group (43.23 versus 22.67 , p < 0.0001). CONCLUSIONS: In elective posterior spinal procedures, the use of barbed sutures significantly reduced the duration of wound closure. The wound healing process was not hindered and the added cost related to the suture material was small.
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Procedimientos Quirúrgicos Electivos , Técnicas de Sutura , Suturas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Suturas/economía , Técnicas de Sutura/instrumentación , Técnicas de Sutura/economía , Procedimientos Quirúrgicos Electivos/métodos , Anciano , Adulto , Estudios Retrospectivos , Columna Vertebral/cirugía , Estudios Prospectivos , Tiempo de Internación/estadística & datos numéricos , Cicatrización de Heridas , Complicaciones Posoperatorias/epidemiologíaRESUMEN
ABSTRACT: Molinari, T, Radaelli, R, Rech, A, Brusco, CM, Markarian, AM, and Lopez, P. Moderators of resistance training effects in healthy young women: A systematic review and meta-analysis. J Strength Cond Res 38(4): 804-814, 2024-To systematically review and analyze the effects of resistance-based exercise programs and potential moderators of change in body fat percentage, whole-body fat and lean mass, muscle hypertrophy, muscle strength, and muscle power/rapid force in healthy young women (between 18 and 35 years). A systematic search was undertaken in 7 databases from inception to May 2022. Eligible randomized controlled trials examined the effects of resistance-based exercise programs on outcomes of interest in healthy young women. Meta-analysis was undertaken with a 3-level mixed-effects model. Associations between standardized mean difference (SMD) and potential moderators (number of sessions, weekly volume, and intensity) were tested by meta-regression models. Statistical significance was set at an α level of 0.05, whereas an α level of 0.05-0.10 was also considered for potential moderators of resistance training effects. Forty articles ( n = 1,312) were included. Resistance-based exercise programs resulted in a significant improvement of 0.4 SMD (95% confidence intervals [95% CI]: 0.2 to 0.5, p < 0.001) in lean mass/muscle hypertrophy and 1.2 SMD (95% CI: 0.9 to 1.5, p < 0.001) in muscle strength. A higher number of sessions was associated with changes in lean mass/muscle hypertrophy ( ß = 0.01 ± 0.00, p = 0.009), whereas a higher weekly volume approached statistical significance to moderate changes in muscle strength ( ß = 0.01 ± 0.01, p = 0.053). Body fat percentage (-0.4 SMD, 95% CI: -0.6 to -0.1, p = 0.006) and muscle power/rapid force (0.6 SMD, 95% CI: 0.2 to 1.1, p = 0.011) were significantly improved. In conclusion, a higher resistance training volume was associated with greater improvements in lean mass/muscle hypertrophy, muscle strength, and body fat percentage, whereas muscle power/rapid force improvements were observed irrespective of prescription characteristics. These findings may help in designing resistance training programs for muscle hypertrophy, strength and power, and body fat percentage in healthy women.
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Entrenamiento de Fuerza , Humanos , Femenino , Entrenamiento de Fuerza/métodos , Estado de Salud , Ejercicio Físico , Fuerza Muscular , HipertrofiaRESUMEN
BACKGROUND: Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic review and network meta-analysis aimed to identify the most effective exercise, physical activity, and dietary interventions to reduce fat mass, body fat percentage and body weight as well as potentially increase lean mass in women diagnosed with or at high risk of breast cancer. METHODS: A systematic search of databases was performed up to May 2022. Eligible randomized controlled trials examined the effects of exercise, physical activity and/or dietary interventions on fat mass and lean mass in women diagnosed with or at high risk of breast cancer. A random-effects network meta-analysis was conducted to determine the effects of different interventions across outcomes when sufficient studies were available. RESULTS: Eighty-four studies (n = 6428) were included in this review. Caloric restriction and combined exercise + caloric restriction significantly reduced fat mass (range, -3.9 to -3.7 kg) and body weight (range, -5.3 to -4.7 kg), whereas physical activity + caloric restriction significantly reduced body fat percentage (-2.4%; 95% confidence interval [CI], -3.4% to -13%) and body mass index (-2.2 kg × m-2 ; 95% CI, -3.0 to -1.4 kg × m-2 ) in breast cancer patients. Resistance exercise was the most effective intervention to increase lean mass (0.7 kg; 95% CI, 0.5-1.0 kg) in breast cancer patients. CONCLUSION: Multimodal exercise and diet programs were the most effective interventions to reduce fat mass, body fat percentage, and body weight and increase and/or preserve lean mass.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/prevención & control , Metaanálisis en Red , Peso Corporal , Ejercicio Físico , Composición CorporalRESUMEN
PURPOSE: The aims of this study were (1) to identify the different food consumption patterns among Spanish preschoolers and (2) to examine the association between having a different food consumption pattern and the odds of having excess weight (i.e., overweight or obesity) or obesity among this population. METHODS: This was a nationwide cross-sectional study with data from the Spanish National Health Survey-2017. All preschoolers (aged 3-5 years) with complete information on all the variables analyzed were selected. The frequency of consumption of the fourteen food groups was evaluated by a food frequency questionnaire. Excess weight/obesity were computed following the World Health Organization criteria. A hierarchical cluster analysis using Ward's method (i.e., based on squared Euclidean distances) and k-means were performed including all food group consumption. A total sample of 663 was included in the cluster analysis. RESULTS: Three different clusters were established. Compared to the healthiest food consumption pattern (Cluster 1), higher odds of excess weight (OR = 1.51; CI: 95%, 1.02-2.25) and obesity (OR = 1.59; CI: 95%, 1.01-2.51) were found for participants with the unhealthiest food consumption pattern (Cluster 3). CONCLUSION: Having a food consumption pattern considered unhealthy (i.e., low intake of vegetables/fruits, high consumption of confectionery products, sugar-sweetened beverages, fast-food, and snacks) was associated with presenting excess weight/obesity among Spanish preschoolers. IMPACT: No studies have examined the specific food consumption patterns associated with excess weight or obesity among Spanish preschoolers. The unhealthiest food consumption pattern was characterized by a food consumption pattern that included a lower intake of vegetables and fruits and a higher consumption of confectionery products, sugar-sweetened beverages, fast-food, and snacks. Having a food consumption pattern considered unhealthy was associated with a higher prevalence of excess weight and obesity in comparison with other healthier food consumption patterns.
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Obesidad , Sobrepeso , Humanos , Estudios Transversales , Obesidad/epidemiología , Sobrepeso/epidemiología , Frutas , Aumento de Peso , DietaRESUMEN
INTRODUCTION: Anderson-Hynes pyeloplasty is the technique of choice for the treatment of pyeloureteral junction obstruction (PUJO) with an excellent success rate. Minimally invasive surgery has become the standard of care for the management of PUJO in children. Although it has been comparable to the open approach at all levels, its diffusion or employment in younger children has not been widely adopted. Our aim is to evaluate laparoscopic pyeloplasty outcomes from international academic centers in children under 1 year of age, focusing on feasibility and outcomes including possible complications. MATERIALS AND METHODS: This is review of consecutive infants under 1 year of age who underwent laparoscopic pyeloplasty between 2009 and 2018 with more than 12 months of follow-up. Seven different training centers with different backgrounds participated in this study. Evaluation was carried out with ultrasound and renogram before and after surgery. Demographic data, perioperative characteristics, complications, and results are described and analyzed. RESULTS: Over 9 years, 124 transperitoneal laparoscopic Anderson-Hynes pyeloplasties were performed on 123 children under 1 year of age; 88 males and 35 females, with 1 case of bilateral PUJO. Of the 124 renal units, 86 were left-sided. Mean age at surgery was 6.6 months (1 week-12 months), with 56% (n = 70) done before 6 months of age. Mean weight at surgery was 6.8 kg (3-12 kg), with 59% (n = 73) weighing less than 8 kg. Mean operative time (skin-to-skin) was 150 min (75-330 min). After a mean follow-up of 46 months (12-84 months), 12 (9%) patients developed complications, with only 1 needing a redo pyeloplasty also done laparoscopically. One child, with deterioration in renal function, underwent nephrectomy. CONCLUSION: Laparoscopic pyeloplasty under 1 year of age and/or less than 12 kilos is feasible with lower complication rate. Furthermore, age younger than 6 months and weight less than 8 kg are no longer limiting factors for a successful pyeloplasty as shown by this multicentre study.
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Hidronefrosis , Pelvis Renal , Laparoscopía , Obstrucción Ureteral , Hidronefrosis/cirugía , Pelvis Renal/anomalías , Pelvis Renal/cirugía , Obstrucción Ureteral/cirugía , Humanos , Masculino , Femenino , Lactante , Procedimientos Quirúrgicos Mínimamente Invasivos , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
The exchange of phosphorus (P) and carbon (C) between plants and arbuscular mycorrhizal fungi (AMF) is a major determinant of their mutualistic symbiosis. We explored the C dynamics in tomato (Solanum lycorpersicum) inoculated or not with Rhizophagus irregularis to study their growth response under different NaH2 PO4 concentrations (Null P, 0 mM; Low P, 0.065 mM; High P, 1.3 mM). The percentage of AMF colonization was similar in plants under Null and Low P, but severely reduced under High P. However, the AMF mass biomarker 16:1ω5 revealed higher fungal accumulation in inoculated roots under Low P, while more AMF spores were produced in the Null P. Under High P, AMF biomass and spores were strongly reduced. Plant growth response to mycorrhiza was negative under Null P, showing reduction in height, biovolume index, and source leaf (SL) area. Under Low P, inoculated plants showed a positive response (e.g., increased SL area), while inoculated plants under High P were similar to non-inoculated plants. AMF promoted the accumulation of soluble sugars in the SL under all fertilization levels, whereas the soluble sugar level decreased in roots under Low P in inoculated plants. Transcriptional upregulation of SlLIN6 and SlSUS1, genes related to carbohydrate metabolism, was observed in inoculated roots under Null P and Low P, respectively. We conclude that P-limiting conditions that increase AMF colonization stimulate plant growth due to an increase in the source and sink strength. Our results suggest that C partitioning and allocation to different catabolic pathways in the host are influenced by AMF performance.
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Micorrizas , Micorrizas/fisiología , Raíces de Plantas/metabolismo , Simbiosis , Plantas , Carbohidratos , LípidosRESUMEN
INTRODUCTION: Acute subdural hematoma (aSDH) is one of the most devastating entities secondary to traumatic brain injury (TBI). Even though radiological computed tomography (CT) findings, such as hematoma thickness (HT), midline shift (MLS), and MLS/HT ratio, have an important prognostic role, they suffer from important drawbacks. We hypothesized that relative cross-sectional area (rCSA) of specific brain regions would provide valuable information about brain compression and swelling, thus being a key determining factor governing the clinical course. METHODS: We performed an 8-year retrospective analysis of patients with moderate to severe TBI with surgically evacuated, isolated, unilateral aSDH. We investigated the influence of aSDH rCSA and ipsilateral hemisphere rCSA along the supratentorial region on the subsequent operative technique employed for aSDH evacuation and patient's clinical outcomes (early death and Glasgow Outcome Scale [GOS] at discharge and after 1-year follow-up). Different conventional radiological variables were also assessed. RESULTS: The study included 39 patients. Lower HT, MLS, hematoma volume, and aSDH rCSA showed a significant association with decompressive craniectomy (DC) procedure. Conversely, higher ipsilateral hemisphere rCSA along the dorso-ventral axis and, specifically, ipsilateral hemisphere rCSA at the high convexity level were predictors for DC. CT segmentation analysis exhibited a modest relationship with early death, which was limited to the basal supratentorial subregion, but could not predict long-term outcome. CONCLUSION: rCSA is an objectifiable and reliable radiologic parameter available on admission CT that might provide valuable information to optimize surgical treatment.
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Lesiones Traumáticas del Encéfalo , Hematoma Subdural Agudo , Humanos , Hematoma Subdural Agudo/cirugía , Estudios Retrospectivos , Pronóstico , Tomografía Computarizada por Rayos X , Hematoma , Resultado del TratamientoRESUMEN
Multivalent glycodendrons are valuable tools to mimic many structural and functional features of cell-surface glycoconjugates and its focal position scaffolds represent important components to increase specificity and affinity. Previous work in our group described the preparation of a tetravalent glucuronic acid dendron that binds with good affinity to Dengue virus envelope protein (KD = 22 µM). Herein, the chemical synthesis and binding analysis of a new library of potent glucuronic acid dendrons bearing different functional group at the focal position and different level of multivalency are described. Their chemical synthesis was performed sequentially in three stages and with good yields. Namely a) the chemical synthesis of the oligo and polyalkynyl scaffolds, b) assembling with fully protected glucuronic acid-based azide units by using a microwave assisted copper-catalysed azide-alkyne cycloaddition reaction and c) sequential deprotection of hydroxyl and carboxylic acid groups. Surface Plasmon Resonance studies have demonstrated that the valency and the focal position functional group exert influence on the interaction with Dengue virus envelope protein. Molecular modelling studies were carried out in order to understand the binding observed. This work reports an efficient glycodendrons chemical synthesis that provides appropriate focal position functional group and multivalence, that offer an easy and versatile strategy to find new active compounds against Dengue virus.
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Virus del Dengue , Dengue , Humanos , Ácido Glucurónico , Azidas/química , Proteínas del Envoltorio Viral , Dengue/tratamiento farmacológicoRESUMEN
PURPOSE: To assess the relationship between particulate matter 2.5 (PM2.5) levels and the prevalence of excess weight in a representative sample of Spanish young people aged 2â14 years. METHODS: This was an ecological cross-sectional study using data from the 2017 wave of the Encuesta Nacional de Salud Española (ENSE), a nationally representative survey of the Spanish young and adult population. The final sample included 4378 young Spanish people (51.0% boys). The weight (kg) and height (cm) of the study participants were proxy-reported by parents or guardians. Excess weight was determined according to the age- and sex-criteria of the International Obesity Task Force. The PM2.5 level was calculated as the annual monitoring data indicator for 2017 among the different regions in Spain. Logistic regression models were performed to estimate the relationships between PM2.5 and weight. RESULTS: Compared to young people located in regions with low levels of PM2.5, those reporting greater odds for excess weight were found in regions with medium PM2.5 (OR = 1.23; 95% CI, 1.02-1.49) and high PM2.5 (OR = 1.35; 95% CI, 1.11-1.64) after adjusting for several sociodemographic, lifestyle and environmental covariates. CONCLUSIONS: The prevalence of excess weight in young people was positively associated with PM2.5 levels in Spain. This finding supports the hypothesis that air pollution exposure can result in excess weight in the young population, which, in turn, might lead to the development of metabolic disorders. From a socioecological perspective, a practical need to take environmental factors into consideration is important to address unhealthy weight in Spanish young people.
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Contaminantes Atmosféricos , Contaminación del Aire , Adulto , Masculino , Humanos , Adolescente , Femenino , Material Particulado/análisis , Estudios Transversales , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/análisis , Aumento de PesoRESUMEN
OBJECTIVE: Our primary aim was to compare muscle morphology (skeletal muscle mass and density) between patients who underwent primary cytoreductive surgery versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer. Secondarily, we explored the associations of muscle morphology with survival outcomes. METHODS: We retrospectively analysed computed tomography (CT) images for 88 ovarian cancer patients (aged 38-89 years) to calculate skeletal muscle index (cm2/m2) and skeletal muscle density (Hounsfield units (HU)). A skeletal muscle index of <38.5 cm2/m2 and skeletal muscle density of <33.7 HU were classified as low. Analyses included repeated measures analysis of covariance and multivariable Cox proportional hazards regression. RESULTS: At baseline, 44.3% of patients had low skeletal muscle index and 50.6% had low skeletal muscle density, with interval surgery patients having significantly lower mean skeletal muscle density than primary surgery patients (32.2±8.9 vs 37.3±8.6 HU, p=0.014). Although both groups had similar reductions in skeletal muscle index following treatment (p=0.49), primary surgery patients had a greater reduction in skeletal muscle density compared with interval surgery patients (-2.4 HU, 95% CI -4.3 to -0.5, p=0.016). Patients who experienced skeletal muscle density loss >2% during treatment (HR 5.16, 95% CI 1.33 to 20.02) and had low skeletal muscle density post-treatment (HR 58.87, 95% CI 3.70 to 935.68) had significantly worse overall survival. CONCLUSION: Low skeletal muscle index and skeletal muscle density were prevalent at ovarian cancer diagnosis. While both groups experienced muscle mass loss, greater reductions in skeletal muscle density occurred in patients undergoing primary surgery. In addition, skeletal muscle density loss during treatment and low skeletal muscle density post-treatment were associated with poorer overall survival. Supportive care involving resistance exercise targeting muscle hypertrophic drive, and nutrition counseling during and after ovarian cancer treatment may help preserve/enhance muscle mass and density.
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Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Humanos , Femenino , Estudios Retrospectivos , Procedimientos Quirúrgicos de Citorreducción/métodos , Músculo Esquelético/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/etiologíaRESUMEN
Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA (n = 60) or placebo (n = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F/MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Niño , Humanos , Aminofenoles/efectos adversos , Benzodioxoles/efectos adversos , Agonistas de los Canales de Cloruro/efectos adversos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Volumen Espiratorio Forzado , MutaciónRESUMEN
A harmonised microbiological survey was performed in two artisanal factories of raw goat milk cheeses (A and B) located in the Andalusian region (Spain). A total of 165 different control points or samples (raw materials, final products, food-contact surfaces [FCS], and air) were examined as microbial and pathogen sources of contamination of artisanal goat raw milk cheeses. For raw milk samples analysed from both producers, the concentrations of aerobic-mesophilic bacteria (AMB), total coliforms, coagulase-positive Staphylococcus spp. (CPS), lactic-acid bacteria (LAB) and moulds and yeasts ranged between 3.48 and 8.59, 2.45-5.48, 3.42-4.81, 4.99-8.59 and 3.35-6.85 log cfu/mL respectively. For the same microbial groups, the analysis of raw milk cheeses revealed concentrations ranging from 7.82 to 8.88, 2.00-6.82, 2.00-5.28, 8.11-9.57 and 2.00-5.76 log cfu/g, respectively. Although the raw material analysed from producer A presented higher microbial loads and between-batch variability, it was B the producer with the most loaded final products. Regarding the microbial air quality, the fermentation area, storage room, milk reception and packaging room were the most AMB loaded places, while the ripening chamber was the area with higher fungal loads in bioareosol from both producers. Conveyor belts, cutting machine, storage boxes and brine tank were highlighted as the most contaminated FCS evaluated. Staphylococcus aureus was the only pathogen detected within the set of 51 isolates from samples as revealed by MALDI-TOF and molecular PCR, with a prevalence of 12.5% for samples from the producer B. The public health risk attributed to the consumption of artisanal goat cheese should not be neglected, and may consider the whole cheesemaking processing chain, from microbiological quality of raw milk to the ready-to-eat final product, especially concerning the presence of S. aureus.
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Queso , Staphylococcus aureus , Animales , Cabras , Microbiología de Alimentos , Hongos/genética , Levaduras , Leche/microbiología , Queso/microbiologíaRESUMEN
INTRODUCTION: This study analyzes the value of PSA kinetics, PSA speed (vPSA), and PSA doubling time (PSAdt), in patients with low-risk prostate cancer who are in an active surveillance (AS) program. METHODS: An observational, retrospective, and longitudinal study of a sample of 86 patients included in AS program between January 2014 and October 2021 was conducted. A review of their medical records was performed, and PSA kinetics were calculated, analyzing the causes of discontinuation of the AS program and its relationship with PSA kinetics. RESULTS: The mean age was 63.39 years, and the median follow-up was 62.55 months. The mean PSA at diagnosis was 8.27 ng/mL. A median of PSAdt of 62.55 months and 1.3 ng/mL/year for vPSA was obtained. 35 patients left the program, with a higher percentage of patients leaving with a PSAdt less than 36 months (73.7 vs. 31.1%) and a vPSA greater than 2 ng/mL/year (68.2 vs. 31.3%). The probability of permanence and the time of permanence in AS were statistically significantly higher for those patients with favorable kinetic parameters. CONCLUSION: PSA kinetics is a parameter to take into account when making decisions to keep patients in an AS program.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Antígeno Prostático Específico/metabolismo , Estudios Retrospectivos , Estudios Longitudinales , Cinética , Espera Vigilante , Neoplasias de la Próstata/diagnóstico , Estudios Observacionales como AsuntoRESUMEN
In the last decade, biosignals have attracted the attention of many researchers when designing novel biometrics systems. Many of these works use cardiac signals and their representation as electrocardiograms (ECGs). Nowadays, these solutions are even more realistic since we can acquire reliable ECG records by using wearable devices. This paper moves in that direction and proposes a novel approach for an ECG identification system. For that, we transform the ECG recordings into Gramian Angular Field (GAF) images, a time series encoding technique well-known in other domains but not very common with biosignals. Specifically, the time series is transformed using polar coordinates, and then, the cosine sum of the angles is computed for each pair of points. We present a proof-of-concept identification system built on a tuned VGG19 convolutional neural network using this approach. We confirm our proposal's feasibility through experimentation using two well-known public datasets: MIT-BIH Normal Sinus Rhythm Database (subjects at a resting state) and ECG-GUDB (individuals under four specific activities). In both scenarios, the identification system reaches an accuracy of 91%, and the False Acceptance Rate (FAR) is eight times higher than the False Rejection Rate (FRR).
Asunto(s)
Arritmias Cardíacas , Identificación Biométrica , Humanos , Redes Neurales de la Computación , Electrocardiografía/métodos , Identificación Biométrica/métodos , Biometría , AlgoritmosRESUMEN
Space technology for small satellites has made significant progress in the academic and industrial fields, and an alternative focused on educational institutions is the CubeSat standard, created to promote various scientific projects of space exploration. In this context, a fundamental module of any satellite is the telemetry subsystem, which controls the communication with the Earth through electronic circuits dedicated to remote communication; also, the measurement and power supply modules are integrated into a CubeSat. Its construction costs range from USD 2500 to 55,000, with suppliers from Europe and the United States. This motivates the development of the present project, aimed at an academic-experimental CubeSat-1U prototype, to limit this technological dependence, focusing on the measurement generated by the acceleration sensors, angular velocity, magnetic fields, barometric pressure, temperature and ultraviolet light intensity, and the energization of each of them. For this, the main objective of the research is to identify the four basic subsystems of the CubeSat-1U: (a) energization subsystem, (b) sensing subsystem, (c) transmission and reception subsystem, and (d) control subsystem. To describe in detail the construction of (a) and (b), a set of diagrams is performed, defining their operation and its interaction. To explain the subsystem's construction, the components selection and integration are presented. As a result, the electrical measurements generated by the power system, the output of the sensors in laboratory conditions, and images of the developed circuits are presented, having as a contribution to the methodology of design, integration, and development of the four subsystems, the feasibility of construction and its implementation in an academic satellite.