64,750 research outputs found

    Comparison of physical fitness between healthy and mild‐to‐moderate asthmatic children with exercise symptoms: A cross‐sectional study

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    .Objective Asthma is a chronic disease that may affect physical fitness, although its primary effects on exercise capacity, muscle strength, functionality and lifestyle, in children and adolescents, are still poorly understood. This study aimed to evaluate the differences in cardiorespiratory fitness, muscle strength, lifestyle, lung function, and functionality between asthmatics with exercise symptoms and healthy children. In addition, we have analyzed the association between clinical history and the presence of asthma. Study Design Cross-sectional study including 71 patients with a diagnosis of asthma and 71 healthy children and adolescents (7–17 years of age). Anthropometric data, clinical history, disease control, lifestyle (KIDMED and physical activity questionnaires), lung function (spirometry), exercise-induced bronchoconstriction test, aerobic fitness (cardiopulmonary exercise test), muscle strength and functionality (timed up and go; timed up and down stairs) were evaluated. Results Seventy-one patients with asthma (mean age 11.5 ± 2.7) and 71 healthy subjects (mean age 10.7 ± 2.5) were included. All asthmatic children had mild to moderate and stable asthma. EIB occurred in 56.3% of asthmatic children. Lung function was significantly (p < .05) lower in the asthmatic group when compared to healthy peers, as well as the cardiorespiratory fitness, muscle strength, lifestyle and functionality. Moreover, asthmatic children were more likely to have atopic dermatitis, allergic reactions, food allergies, and a family history of asthma when compared to healthy children. Conclusions Children with mild-to-moderate asthma presenting exercise symptoms show a reduction in cardiorespiratory fitness, muscle strength, lung function, functionality, and lifestyle when compared to healthy peers. The study provides data for pediatricians to support exercise practice aiming to improve prognosis and quality of life in asthmatic children.S

    Accuracy of the Logistic EuroSCORE in Predicting Long-Term Survival Following Isolated Aortic Valve Replacement

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    Objective: To assess the ability of the logistic EuroSCORE to predict long- term mortality of patients undergoing isolated Surgical Aortic Valve Replacement (SAVR). Methods: A retrospective review of all patients undergoing SAVR between September 1999, and March 2018 was done. Results: 2018 patients were eligible for inclusion in the study. Patients were grouped according to risk: low (n = 506), intermediate (n = 609), and high-risk (n = 903) depending on their logistic EuroSCORE values. The 30-day mortality of the low- risk group was 0.47%. The one-, five-, 10-, 15-, and 20-year mortality was 1.66%, 4.9%, 14.9%, 24.3%, and 43.8%, respectively. Intermediate-risk group 30-day mortality was 0.66%. The one-, five-, 10-, 15-, and 20-year mortality was 3.28%, 11.9%, 32%, 54.8%, and 82.6%, respectively. The 30-day mortality of the high- risk group was 3.99%. The one-, five-, 10-, 15-, and 20-year mortality was 8.2%, 27%, 55.4%, 78.6%, and 87%, respectively. Conclusion: Our results confirm that the lES is accurate in predicting long-term mortality outcomes of SAVR. This real-world data provides evidence of the potential usefulness of the EuroSCORE to help the heart team and patients decide on appropriate interventions for aortic stenosis

    Design, synthesis and biological evaluation of novel pyrazolopyrimidines for the treatment of glioblastoma multiforme

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    In 2020, cancer was the leading cause of early death in over 57 countries, accounting for approximately 10 million deaths worldwide. Brain cancers remain one example of greatest unmet need, with on average 14% survival 10 years post-diagnosis. Glioblastoma multiforme (GBM) is the most common and aggressive type of brain cancer in adults, with an average prognosis of 12 months. Current treatments only extended the average prognosis by 2 months. GBM is characterised by a complex set of mutations, with significant disruption to kinase pathways, specifically RTK signalling. Drug design in the past 30 years has predominately been target-based, focussing on the development of highly selective molecules that act against specific biological targets. Parallel to this, the rate of attrition – the number of compounds that fail in the clinics because of poor physicochemical properties – has greatly increased. For complex cancers, a targeted approach is not sufficient to discover new therapies. Phenotypic drug discovery, where compounds are designed based on defined pharmacological endpoints, without prior knowledge of the molecular target, was used to develop new compounds for the improved treatment of glioblastoma. Libraries of anticancer compounds based on the pyrazolo[3,4-d]pyrimidine scaffold have been designed for the treatment of glioblastoma. Compounds were synthesised in a convergent manner, and data from phenotypic screens against glioma cell-lines were used to build up structure-activity-relationships, facilitating further rounds of design and optimisation. Over 230 novel molecules were designed, synthesised, and screened, identifying several lead molecules with low-micromolar potencies. Further evaluation of lead molecules in cancer models and target deconvolution studies identified lead compounds that demonstrated preferential activity against the mesenchymal sub-type of glioblastoma. Whilst the target of the best lead compounds remains unknown, two selective inhibitors of CSF-1R kinase were identified through kinase screening

    Desarrollo de una batería de memoria semántica para pacientes con epilepsia del lóbulo temporal

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    La epilepsia focal más frecuente es aquella epilepsia cuyo foco epileptógeno está localizado en el lóbulo temporal medial y es secundaria a una esclerosis con atrofia de la región amígdalo-hipocámpica, con una red epileptógena que abarca la porción anterior del lóbulo temporal. En ocasiones los pacientes requieren de un tratamiento quirúrgico que incluye la resección unilateral de ambas regiones, tanto del polo anterior, como del complejo amígdala-hipocampo. Estas estructuras han demostrado tener gran importancia para el procesamiento de la memoria semántica (región anterotemporal) y episódica (región amígdalo-hipocámpica), por lo que los pacientes que son sometidos a esta intervención suelen presentar quejas cognitivas relacionadas con ambos tipos de memoria. Sin embargo, parece que las evaluaciones neuropsicológicas que realizamos de forma rutinaria en las diferentes Unidades de Epilepsia no son capaces de detectar todos los problemas cognitivos que ocurren en estos pacientes ya que, a pesar de las dificultades expresadas por estos, las evaluaciones no muestran alteraciones. La hipótesis principal del presente trabajo es que estas quejas se deben a tipos de memoria que no están incluidos en las pruebas neuropsicológicas actuales y, por tanto, no somos capaces de identificar bien sus problemas. En primer lugar, se propone que la memoria semántica está afectada, pero solamente para palabras de baja frecuencia de uso en la vida diaria, no analizadas en las evaluaciones convencionales actuales. En segundo lugar, otros problemas no objetivados se deben a un problema de la memoria de consolidación, medida como olvido a largo plazo acelerado que se detecta cuando se amplia el periodo de evaluación del recuerdo. Además, estas alteraciones van a manifestarse con mayor intensidad en pacientes cuyo foco epileptógeno está localizado en el lóbulo temporal izquierdo. Los objetivos fundamentales de este trabajo son evaluar en pacientes con epilepsia del lóbulo temporal medial intervenidos quirúrgicamente mediante lobectomía temporal anterior con amigdalohipocampectomía la presencia de alteraciones de la memoria verbal tanto semántica como episódica, así como conocer su valor lateralizador según el hemisferio afectado. El estudio se basó en la comparación de pacientes con epilepsia del lóbulo temporal (ELT) tratados con lobectomía temporal anterior con amigdalohipocampectomía con un grupo control de personas sanas, comparables respecto a edad, nivel educativo y coeficiente intelectual (CI). Las pruebas de memoria semántica mostraron que únicamente los pacientes con ELT izquierda tenían alteraciones, especialmente para ítems de baja frecuencia y tanto en tares de expresión como de comprensión verbal. Asimismo, el tiempo de reacción fue mayor en el grupo de pacientes con ELT izquierda para todos los ítems y únicamente para las palabras o conceptos de baja frecuencia en aquellos con ELT derecha. Además, se incluyó una prueba de memoria episódica estándar (RAVLT) que en lugar de restringir la evaluación a 30 minutos, se evaluó a 7 días para medir el olvido a largo plazo. Los resultados mostraron que los dos grupos de pacientes, tanto los de ELT izquierda como aquellos con ELT derecha, desarrollaron olvido a largo plazo. Por último los resultados mostraron que la presencia de crisis epilépticas no afectó a la presencia de olvido a largo plazo acelerado

    The Genetics of Pain: An exploration of gene-by-environment interactions and their effects on pain

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    The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood experience (ACE) reported significantly higher scores than minor allele carriers with at least one ACE. For pain interference, minor allele carriers (G/G) of CNR2 rs2501431 scored significantly higher than major allele carriers (A/A and G/A). Chapter 3 presents a cluster analysis that combines genotypes of FKBP5 rs9394314 and CNR2 rs2501431 to explore meaningful relationships with pain and trauma-related distress. ACE was also explored as a moderator of these relationships. Three clusters were identified where the second cluster characterized by major allele carriers of rs9394314 and minor allele carriers of rs2501431 reported significantly higher pain-related functional interference scores. Participants in the second cluster with at least one ACE reported higher pain interference and traumatic distress scores compared to the third cluster, while participants in the first cluster with at least one ACE reported higher pain severity compared to the first cluster. Chapter 4 presents genomic structural equation models (SEM) that explore the relationships of genotypes with trauma-related distress using the traumatic injuries distress scale (TIDS), ACE, and recovery outcomes. The results demonstrate a relationship between TIDS and recovery outcomes, and an indirect relationship between FKBP5 rs9394314 and recovery outcomes exist which is mediated by TIDS. Major allele carriers of FKBP5 rs9394314 reported higher TIDS scores, which was also demonstrated for participants that had at least one ACE. Major allele carriers that scored higher on the TIDS were predicted to be in the none-recovered category. These results support the notion that gene-x-environment interactions may play an important role in pain and recovery

    Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2

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    Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients

    RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes

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    MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy. HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD). PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies. In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD. To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells. To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression. In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies


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    Masalah dalam penelitian ini yaitu, fenomena model pembelajaran blended learning di Era Pandemi covid-19. Rumusan masalah dalam penelitian ini adalah (i) Bagaimana gambaran pelaksanaan pembelajaran blended learning pada Era Pandemi Covid-19 di SDN 151 Inpres Sabantang Kecamatan Tanralili Kabupaten Maros ? (ii) Apa hambatan dan faktor pendukung pelaksanaan pembelajaran berbasis blended learning learning pada Era Pandemi Covid19.Penelitian ini menggunakan pendekatan kualitatif dengan model studi kasus yang bermaksud untuk mendeskripsikan pelaksanaan pembelajaran berbasis blended learning Teknik pengumpulan data dalam penelitian ini dilakukan dengan angket, wawancara dan dokumentasi. Hasil penelitian ini menunjukkan bahwa (i) pelaksanaan pembelajaran berbasis blended learning pada Era Pandemi Covid-19 di SDN 151 Inpres Sabantang Kecamatan Tanralili Kabupaten Maros, seuai dengan dengan sintaks atau tahapan pelaksanaan pada pembelajaran blended learning (ii) hambatan pelaksanaan pembelajaran blended learning dari ketiga subjek menyatakan waktu yang relative singkat dalam proses pembelajaran, kurikulum masa darurat yang belum optimal,biaya kuota internet yang mahal namun dibalik hambatan factor pendukung tetap ada dari pihak pemerintah,Tenaga pendidik dan wilayah/lokasi sekolah. Kata Kunci : Pandemi, Pembelajaran Blended Learnin
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