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OBJECTIVES: Non-contrast computed tomography of the brain (NCCTB) is commonly used to detect intracranial pathology but is subject to interpretation errors. Machine learning can augment clinical decision-making and improve NCCTB scan interpretation. This retrospective detection accuracy study assessed the performance of radiologists assisted by a deep learning model and compared the standalone performance of the model with that of unassisted radiologists. METHODS: A deep learning model was trained on 212,484 NCCTB scans drawn from a private radiology group in Australia. Scans from inpatient, outpatient, and emergency settings were included. Scan inclusion criteria were age ≥ 18 years and series slice thickness ≤ 1.5 mm. Thirty-two radiologists reviewed 2848 scans with and without the assistance of the deep learning system and rated their confidence in the presence of each finding using a 7-point scale. Differences in AUC and Matthews correlation coefficient (MCC) were calculated using a ground-truth gold standard. RESULTS: The model demonstrated an average area under the receiver operating characteristic curve (AUC) of 0.93 across 144 NCCTB findings and significantly improved radiologist interpretation performance. Assisted and unassisted radiologists demonstrated an average AUC of 0.79 and 0.73 across 22 grouped parent findings and 0.72 and 0.68 across 189 child findings, respectively. When assisted by the model, radiologist AUC was significantly improved for 91 findings (158 findings were non-inferior), and reading time was significantly reduced. CONCLUSIONS: The assistance of a comprehensive deep learning model significantly improved radiologist detection accuracy across a wide range of clinical findings and demonstrated the potential to improve NCCTB interpretation. CLINICAL RELEVANCE STATEMENT: This study evaluated a comprehensive CT brain deep learning model, which performed strongly, improved the performance of radiologists, and reduced interpretation time. The model may reduce errors, improve efficiency, facilitate triage, and better enable the delivery of timely patient care. KEY POINTS: ⢠This study demonstrated that the use of a comprehensive deep learning system assisted radiologists in the detection of a wide range of abnormalities on non-contrast brain computed tomography scans. ⢠The deep learning model demonstrated an average area under the receiver operating characteristic curve of 0.93 across 144 findings and significantly improved radiologist interpretation performance. ⢠The assistance of the comprehensive deep learning model significantly reduced the time required for radiologists to interpret computed tomography scans of the brain.
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Aprendizado Profundo , Adolescente , Humanos , Radiografia , Radiologistas , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , AdultoRESUMO
Antimicrobial resistance (AMR) is predicted to cause a worldwide annual toll of 10 million deaths by 2050. This looming public health threat has been linked to antibiotic overuse and pollution, which places selective pressures on AMR maintenance and transfer in and between microbial populations. We examined the distribution, diversity and potential mobility of AMR genes in cyanobacteria. While cyanobacteria are not pathogenic, we hypothesised that they could be a major environmental reservoir for AMR genes. Genes encoding AMR to seven antimicrobial drug classes were found in 10% of cyanobacterial genomes. AMR genes were found in 13% of freshwater, 19% of terrestrial, 34% of symbiotic, 2% of thermal spring, and 3% of marine genomes. AMR genes were found in five cyanobacterial orders with 23% of Nostocales and 8% of Oscillatoriales strains containing AMR genes. The most frequently observed alleles were ansamycin resistance genes, which were present in 7% of strains. AMR genes responsible for resistance to broad-spectrum ß-lactams, chloramphenicols, tetracyclines, macrolides, and aminoglycosides were associated with mobile genetic elements or plasmid replicons or both. These results suggest that cyanobacteria are an extensive reservoir, and potential vector, for AMR genes in diverse terrestrial and aquatic habitats.
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Anti-Infecciosos , Cianobactérias , Antibacterianos/farmacologia , Plasmídeos/genética , Saúde Pública , Cianobactérias/genéticaRESUMO
BACKGROUND: Diabetes mellitus is one of the most common diseases worldwide with significant morbidity and mortality. HbA1c remains one of the most important methods for diagnosis and monitoring of the disease. Since HbA1c is a reflection of the glucose attached to red blood cells, factors affecting hemoglobin and red blood cells' half-life can influence HbA1c measurements. OBJECTIVE: This study aims to evaluate the effect of different types of anemia including iron deficiency anemia, sickle cell anemia, ß -thalassemia trait, and megaloblastic anemia on HbA1c levels in a tertiary hospital over the past 6 years (2016-2022). METHOD: This is a retrospective chart review study of 324 patients including those with one of the four types of anemia mentioned above and a control group. The control group were healthy adults with normal HbA1c and hemoglobin, who were not known to have diabetes or anemia. Patients with diabetes or prediabetes based on self-reporting or elevated fasting, random blood sugar, or 2 hours post-prandial blood glucose were excluded. RESULTS: The mean HbA1c levels were significantly higher in sickle cell anemia at 5.83% (95% CI = 5.39-6.28) and in iron deficiency anemia at 5.75% (95% CI = 5.68-5.82) when compared to the control group at 5.32% (95% CI = 5.22-5.41). However, the mean HbA1c levels in megaloblastic anemia were 5.38% (95% CI = 5.26-5.5) and 5.45% (95% CI = 5.21-5.69) in beta thalassemia trait, which were not significantly different when compared to the control group. HbA1c significantly decreased from 5.75 to 5.44% after treatment in the iron-deficient group with a p-value of < 0.001. Moreover, lower hemoglobin and higher red cell distribution width correlated with higher HbA1c levels in patients with sickle cell anemia. CONCLUSION: This study found a significant increase in HbA1c levels in iron deficiency anemia and sickle cell disease in patients not known to have diabetes. However, there was no significant effect in those patients with ß-thalassemia trait and megaloblastic anemia. Treatment of iron deficiency anemia significantly decreased the HbA1c level, bringing it back to normal.
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Anemia Ferropriva , Anemia Megaloblástica , Anemia Falciforme , Diabetes Mellitus , Talassemia beta , Adulto , Humanos , Hemoglobinas Glicadas , Anemia Ferropriva/diagnóstico , Estudos Retrospectivos , Hemoglobinas , Diabetes Mellitus/diagnóstico , Talassemia beta/complicações , Talassemia beta/diagnósticoRESUMO
BACKGROUND: COVID-19 is no longer a global public health emergency, but it still affects numerous diseases and needs further research. Diabetic COVID-19 patients with major complications or intensive care had high mortality rates. This review provides pathophysiological descriptive data on diabetes mellitus type 2 and shows how COVID-19 infection in Saudi Arabia predicts disease severity and prognosis. METHODS: This review was conducted through online research on MEDLINE/PubMed databases, Scopus, and Web of Science based on links between COVID-19 and diabetes mellitus type 2 patients. By using the keywords 'COVID-19', 'diabetes', ' correlation', and impact on 'population' from December 2022 to February 2023. The full texts of the articles that were retrieved were accessed. RESULTS: The COVID-19 epidemic has affected the community, especially diabetics, and their daily life. According to our research on prior studies, most COVID-19 patients in Saudi Arabia had diabetes as a comorbidity. CONCLUSIONS: We underline the necessity of thorough study to better understand COVID-19 and its association with diabetes to design and implement evidence-based initiatives and policies in Saudi Arabia, where diabetes is a major health issue.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , COVID-19/epidemiologia , Comorbidade , Prognóstico , Arábia Saudita/epidemiologiaRESUMO
BACKGROUND: Falls secondary to balance disturbances have been considered as a burden on health systems in people with dementia aged above 65. Exercise has been increasingly recommended to address such problem and the main challenges being the commitment and supervision of training. The study's aim was to investigate the effect of adding motorized cycle ergometer (MCE) on high intensity functional exercise (HIFE) training on balance and cognition in older adults with dementia. METHODS: Sixty participants over the age of 65 were randomly allocated into 3 groups, Mo, Ex, and MoEx undergoing, respectively, 50 minutes MCE, HIFE, or combination of both. Sessions were done 3 times per week for 12 weeks. Outcome measures taken before and after study period were Berg Balance Scale (BBS), timed up and go test (TUG), and Mini Mental State Exam (MMSE). RESULTS: All groups showed significant improvement in BBS scores but not on TUG or MMSE scores. Between group analysis showed no privilege of any used training methods over the other for all measures taken. CONCLUSIONS: Training with HIFE, MCE, or combination of both is effective in improving balance but not cognition. However, MCE can be an alternative to supervised exercise training in addressing balance.
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Demência , Equilíbrio Postural , Humanos , Idoso , Envelhecimento , Estudos de Tempo e Movimento , Exercício FísicoRESUMO
Introduction: Children present with a spectrum of renal diseases depending on age, sex, and geographic location among other factors. With the absence of a paediatric renal registry in Nigeria, this will provide part of the regional data necessary for the Nigerian renal registry. Methodology: A retrospective study where cases of renal diseases that presented in a nephrology clinic over a 2-year period were retrieved from the nurses' and doctors' records and analysed. Results: A total of 147 children were reviewed, male and female were 101 and 46 respectively with M: F being 2.2: 1. Mean age was 9.59 ± 4.58 years, age distribution were <5 years (23.0; 15.6%), 5-9 years (52; 35.4%) and ≥ 10 years (72.0; 49.0%). The majority (77.0; 52.4%) had low socioeconomic status. Majority (145; 98.6%) were acquired renal diseases while ectopic kidney (2.0; 1.4%) was the only CAKUT. Acute glomerulonephritis (49; 33.3%), urinary tract infections (37; 25.2%) and nephrotic syndrome (30.0; 20.4%) were the major acquired renal diseases. Acute kidney injury (AKI) and chronic kidney disease (CKD) were seen in 9 (6.1%) and 13 (8.8%) respectively. Urolithiasis, sickle cell nephropathy, and primary enuresis were seen in 5(3.4%) and 1 (0.7%) respectively. The mean age of children with CAKUT and acquired renal diseases were13.00 ±1.41 and 9.54±4.59 years (P=0.290) while that of AKI and CKD were 10.89±5.21 and 14.15±3.24 years respectively (P= 0.084). Conclusion: Childhood renal diseases increase with age and are more common among adolescents, especially the chronic forms. Regular screening and aggressive treatment are recommended in adolescents.
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Injúria Renal Aguda , Nefrologia , Insuficiência Renal Crônica , Adolescente , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Estudos Retrospectivos , Hospitais de Ensino , Insuficiência Renal Crônica/epidemiologiaRESUMO
OBJECTS: Cushing's disease (CD) is the most common cause of ACTH-dependent hypercortisolism in children age ≥ 7. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children. We present a case series of children with ACTH-dependent hypercortisolemia and review the literature to assess the utility of BIPSS in the diagnosis and localization of CD. METHODS: We performed an IRB-approved chart review of patients aged ≤ 18 with ACTH-dependent hypercortisolism at MGH between 2000 and 2019 and collected clinical, laboratory, radiographic, BIPSS, surgical, and outcomes data. RESULTS: In our cohort (n = 21), BIPSS had a sensitivity of 93% and specificity of 100% for diagnosis of CD. Compared to surgery, successful BIPSS correctly predicted adenoma laterality in 69% of cases vs. 70% by MRI. Among patients with lesions ≥ 4 mm (n = 9), BIPSS correctly lateralized in 50% vs. 100% by MRI. In patients with subtle lesions (< 4 mm, n = 7), BIPSS correctly lateralized in 80% vs. 71% by MRI. In patients (n = 4) with CD and negative MRIs, BIPSS correctly lateralized in 75% cases. Surgical cure was achieved in 90% of patients and 95% of patients had long-term disease control. CONCLUSIONS: In our cohort (n = 21; n = 20 CD, n = 1 ectopic ACTH secretion), BIPSS was sensitive and specific for the diagnosis of CD. Compared to MRI, BIPSS was not additionally helpful for lateralization in patients with lesions ≥ 4 mm on MRI. BIPSS was helpful in guiding surgical exploration and achieving immediate postoperative remission among patients with subtle and negative MRI findings.
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Hormônio Adrenocorticotrópico/sangue , Hipofisectomia/métodos , Amostragem do Seio Petroso/métodos , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Adolescente , Índice de Massa Corporal , Feminino , Humanos , Hidrocortisona/urina , Imageamento por Ressonância Magnética/métodos , Masculino , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Indução de Remissão/métodos , Reprodutibilidade dos Testes , Tempo , Resultado do TratamentoRESUMO
This paper investigates the performance of one-eighth Spherical Fraction Microphone Array through experimental measurement to analyze acoustic scenes in one-eighth of space. The array geometry is designed to be placed in a room corner at the junction of three acoustically rigid walls. Two prototypes are built with 8 and 16 microphones, respectively. The sampling strategy is discussed and a spatial aliasing analysis is carried out both analytically and by numerical simulations. The array performances are evaluated through Spherical Fraction Beamforming (SFB). This approach is based on the decomposition of the acoustic pressure field in a rigid bounded domain. The localization angular error and Directivity Index criterion are evaluated for both arrays. In a first experiment, the arrays are mounted in an eighth of space built inside an anechoic room. The results are compared with simulation and show consistency. The theoretical limitations of SFB in a rigid bounded one-eighth of space are retrieved experimentally. These limitations are also observed in a real configuration: an office room. Further investigations on SFB are also conducted in the case of a virtual scene constructed with two sound sources.
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The effects of a silver nanoparticles (AgNPs)-cow-dung combination on Abelmoschus esculentus physiology, enzyme activities, heavy metal bioaccumulation, and micronutrients were investigated. A. esculentus seedlings were nurtured with foliar application of water, 0.75 mg/L each of AgNPs, cow-dung and AgNPs-cow dung till maturity. AgNPs-cow dung inhibited root and shoot lengths by 12.9% and 24.8%, respectively as opposed to elongation recorded for individual application compared to the control. In contrast to the promotion of photosynthesis, enzyme and antioxidant activities by individual applications, AgNPs-cow dung suppressed more than 50% of these parameters. Implied toxicities of AgNPs-cow dung on A. esculentus manifested in increased malondialdehyde contents with concomitant higher bioaccumulation factor of heavy metals. Cow-dung and AgNPs each stimulated A. esculentus activities in different ways, but their combination was inhibitory, which may be ascribed to the transformed AgNPs in cow-dung and relative availability of toxic metals.
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Abelmoschus , Nanopartículas Metálicas , Metais Pesados , Animais , Bovinos , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo , Metais Pesados/toxicidadeRESUMO
The versatility of silicon photonic integrated circuits has led to a widespread usage of this platform for quantum information-based applications, including quantum key distribution (QKD). However, the integration of simple high-repetition-rate photon sources is yet to be achieved. The use of weak-coherent pulses (WCPs) could represent a viable solution. For example, measurement device independent QKD (MDI-QKD) envisions the use of WCPs to distill a secret key immune to detector side channel attacks at large distances. Thus, the integration of III-V lasers on silicon waveguides is an interesting prospect for quantum photonics. Here we report the experimental observation of Hong-Ou-Mandel interference with 46±2% visibility between WCPs generated by two independent III-V on silicon waveguide integrated lasers. This quantum interference effect is at the heart of many applications, including MDI-QKD. This Letter represents a substantial first step towards an implementation of MDI-QKD fully integrated in silicon and could be beneficial for other applications such as standard QKD and novel quantum communication protocols.
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The extraction of phenolic compounds from canola meal produces functional health products and renders the canola meal a more digestible animal feed. The extracted phenolics may have novel bioactivity worth investigation. In this study, several solvents were evaluated for their ability to extract phenolic compounds from canola meal: water (WE) and various 80% organic solvent/water mixtures of methanol (ME), acetone (AE), ethanol (EE), butanol (BE), chloroform (CE) and hexane (HE). The in vitro antioxidant and anti-obesity properties of various extracts were investigated. Anti-obesity properties were studied using adipogenic differentiation inhibition of a murine mesenchymal stem cell line (C3H10T1/2) and a pancreatic lipase inhibition assay. AE, ME, and BE showed significant (p < 0.05) adipogenesis and pancreatic lipase inhibitory activities and may have more pharmacological properties. AE down-regulated the gene expression of the major adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), correlating to phenolic content in a dose-dependent manner. The chemical characterization of AE revealed the presence of sinapic acid, ferulic acid, and kaempferol derivatives as main bioactive phenols.
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Adipogenia/efeitos dos fármacos , Antioxidantes/farmacologia , Brassica napus/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Regulação da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/metabolismo , Lipase/antagonistas & inibidores , Lipase/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , PPAR gama/genética , Fenóis/química , Extratos Vegetais/química , Solventes , Espectrometria de Massas em TandemRESUMO
OBJECTIVES: This study was conducted to assess household coverage with iodized salt in Saudi Arabia, and to determine adequacy of salt iodization. METHODS: A school-based cross-sectional study using WHO 30-cluster survey methodology. RESULTS: Analysis of 4242 salt samples using qualitative rapid test kit (RTK) revealed that 68.7% (95% CI 67.3-70.1%) were iodized with significant regional differences (p < 0.001). The highest iodized salt samples came from Makkah (82.3%), Riyadh (81.1%) and Maddinah (76.2%) regions, while the least iodized salt samples came from Hail (31.3%), Baha (53.0%), and Northern Borders (57.5%) regions. The national weighted proportion of households consuming iodizes salt was 69.8% (95% CI 69.4-71.2), which is below the Universal Salt Iodization (USI) goal (≥90% coverage). For validation, a quantitative iodometric titration method was used to analyze 775 representative salt samples screened iodized by RTK; iodine content of ≥15 ppm was found in 95.2% (95% CI 93.9-96.5) of samples with median iodine content 51 ppm (mean 50.4 ± 21.8). More than 70% of the iodized salt samples contained iodine concentration higher than the recommended national level (15-40 ppm). CONCLUSIONS: The study revealed inadequate consumption of iodized salt among Saudi households and explored marked regional heterogeneity. The majority of iodized salt samples contained iodine concentration more than the recommended level. These findings imply the need to launch a public awareness campaign on use of iodized salt. Legislation to ban production and sale of non-iodized salt sale for human consumption might be considered. A well-functioning monitoring system at factory level and surveillance system are crucially needed to ensure proper salt iodization and intake.
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Iodo/análise , Necessidades Nutricionais , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/análise , Conscientização , Criança , Estudos Transversais , Características da Família , Feminino , Educação em Saúde , Humanos , Iodo/administração & dosagem , Iodo/deficiência , Legislação sobre Alimentos , Masculino , Política Nutricional/legislação & jurisprudência , Arábia Saudita , Instituições Acadêmicas , EstudantesRESUMO
Alzheimer's disease (AD) is a major neurodegenerative disease, associated with the hallmark proteinacious constituent called amyloid beta (Aß) of senile plaques. Moreover, it is already established that metals (particularly copper, zinc and iron) have a key role in the pathogenesis of AD. In order to reduce the Aß plaque burden and overcome the side effects from the synthetic inhibitors, the current study was designed to focus on direct inhibition of with or without metal-induced Aß fibril formation and aggregation by using olive biophenols. Exposure of neuroblastoma (SH-SY5Y) cells with Aß42 resulted in decrease of cell viability and morphological changes might be due to severe increase in the reactive oxygen species (ROS). The pre-treated SH-SY5Y cells with olive biophenols were able to attenuate cell death caused by Aß42, copper- Aß42, and [laevodihydroxyphenylalanine (l-DOPA)] l-DOPA-Aß42-induced toxicity after 24 h of treatment. Oleuropein, verbascoside and rutin were the major anti-amyloidogenic compounds. Transgenic mice (APPswe/PS1dE9) received 50 mg/kg of oleuropein containing olive leaf extracts (OLE) or control diet from 7 to 23 weeks of age. Treatment mice (OLE) were showed significantly reduced amyloid plaque deposition (p < 0.001) in cortex and hippocampus as compared to control mice. Our findings provide a basis for considering natural and low cost biophenols from olive as a promising candidate drug against AD. Further studies warrant to validate and determine the anti-amyloid mechanism, bioavailability as well as permeability of olive biophenols against blood brain barrier in AD.
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Doença de Alzheimer/tratamento farmacológico , Glucosídeos/farmacologia , Iridoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Rutina/farmacologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Linhagem Celular Tumoral , Glucosídeos/uso terapêutico , Humanos , Glucosídeos Iridoides , Iridoides/uso terapêutico , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Olea/química , Fenóis/uso terapêutico , Presenilinas/genética , Rutina/uso terapêuticoRESUMO
Plant biophenols have been shown to be effective in the modulation of Alzheimer's disease (AD) pathology resulting from free radical-induced oxidative stress and imbalance of the redox chemistry of transition metal ions (e.g., iron and copper). On the basis of earlier reported pharmacological activities, olive biophenols would also be expected to have anti-Alzheimer's activity. In the present study, the antioxidant activity of individual olive biophenols (viz. caffeic acid, hydroxytyrosol, oleuropein, verbascoside, quercetin, rutin and luteolin) were evaluated using superoxide radical scavenging activity (SOR), hydrogen peroxide (H2O2) scavenging activity, and ferric reducing ability of plasma (FRAP) assays. The identification and antioxidant activities in four commercial olive extracts-Olive leaf extractTM (OLE), Olive fruit extractTM (OFE), Hydroxytyrosol ExtremeTM (HTE), and Olivenol plusTM (OLP)-were evaluated using an on-line HPLC-ABTSâ¢+ assay, and HPLC-DAD-MS analysis. Oleuropein and hydroxytyrosol were the predominant biophenols in all the extracts. Among the single compounds examined, quercetin (EC50: 93.97 µM) and verbascoside (EC50: 0.66 mM) were the most potent SOR and H2O2 scavengers respectively. However, OLE and HTE were the highest SOR (EC50: 1.89 µg/mL) and H2O2 (EC50: 115.8 µg/mL) scavengers among the biophenol extracts. The neuroprotection of the biophenols was evaluated against H2O2-induced oxidative stress and copper (Cu)-induced toxicity in neuroblastoma (SH-SY5Y) cells. The highest neuroprotection values (98% and 92%) against H2O2-induced and Cu-induced toxicities were shown by the commercial extract HTETM. These were followed by the individual biophenols, caffeic acid (77% and 64%) and verbascoside (71% and 72%). Our results suggest that olive biophenols potentially serve as agents for the prevention of neurodegenerative diseases such as AD, and other neurodegenerative ailments that are caused by oxidative stress.
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Olea/química , Antioxidantes/farmacologia , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Linhagem Celular Tumoral , Cobre/farmacologia , Sequestradores de Radicais Livres/metabolismo , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Glucosídeos Iridoides , Iridoides/química , Iridoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/química , Quercetina/farmacologiaRESUMO
BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.
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Antivirais/uso terapêutico , Ebolavirus/genética , Doença pelo Vírus Ebola/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , RNA Viral/genética , Terapêutica com RNAi/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ebolavirus/patogenicidade , Feminino , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/genética , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/virologia , Interações Hospedeiro-Patógeno , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nanopartículas , RNA Interferente Pequeno/administração & dosagem , RNA Viral/sangue , Terapêutica com RNAi/efeitos adversos , Serra Leoa , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Adulto JovemRESUMO
Stress hormones might represent a key link between individual-level infection outcome, population-level parasite transmission, and zoonotic disease risk. Although the effects of stress on immunity are well known, stress hormones could also affect host-vector interactions via modification of host behaviours or vector-feeding patterns and subsequent reproductive success. Here, we experimentally manipulated songbird stress hormones and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors in addition to defensive behaviours of hosts. Despite being more defensive, birds with elevated stress hormone concentrations were approximately twice as likely to be fed on by mosquitoes compared to control birds. Moreover, stress hormones altered the relationship between the timing of laying and clutch size in blood-fed mosquitoes. Our results suggest that host stress could affect the transmission dynamics of vector-borne parasites via multiple pathways.
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Corticosterona/sangue , Culicidae/fisiologia , Comportamento Alimentar , Tentilhões/sangue , Estresse Fisiológico , Animais , Tentilhões/parasitologia , Insetos Vetores/fisiologia , ZoonosesRESUMO
Field studies of the ecology of eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus) in the southeastern United States have demonstrated that Culex erraticus (Dyar and Knab) is the most common mosquito at many enzootic sites and is often infected with the virus. However, the competence of Cx. erraticus for EEEV has not been explored in detail. Culex erraticus females were collected from the field and fed upon EEEV-infected chicks. The infected mosquitoes were provided honey for nutrition and to monitor for time to infectiveness. Of the mosquitoes that survived the 14-d postfeeding period, 89% were infected and 84% had evidence of a disseminated infection, though titers were generally low. EEEV was first detected in honey 6 d postinfection and was detected in samples collected from 94% of the mosquitoes with a disseminated infection overall. These data and others were then employed to estimate the relative vectorial capacity of Cx. erraticus at an EEEV enzootic site in Alabama. The vectorial capacity of Cx. erraticus at this site was 44% of Culiseta melanura (Coquillett), the accepted enzootic vector, suggesting Cx. erraticus may play a role in transmitting EEEV in areas where it is abundant and Cs. melanura rare.
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Culex/virologia , Vírus da Encefalite Equina do Leste/fisiologia , Insetos Vetores/virologia , Animais , Feminino , Sudeste dos Estados UnidosRESUMO
INTRODUCTION: Left ventricular assist devices (LVADs) are increasingly common in patients with advanced heart failure. GI bleeding (GIB) occurs in 20-30 % of these patients and can arise anywhere in the GI tract. Given the high rates of GIB in this population, our aim was to determine the diagnostic yield of repeated endoscopic evaluation in these patients. METHODS: We performed a retrospective review of all 257 patients who had LVADs placed between 2008 and 2013 at Duke University Hospital and identified all patients who underwent any endoscopic evaluation for GIB. RESULTS: Of the 257 patients with LVADs placed, 78 (30 %) underwent at least one endoscopy for GIB. A source was identified in 36 % of cases, most commonly angioectasias (53.6 %). Treatment was performed in 67.9 % of patients and hemostasis was achieved in all. 64.1 % of the cohort underwent a second endoscopy for GIB. 42.9 % of these exams revealed a bleeding source. Endoscopic treatment was employed in 76.2 %. 38.5 % of the cohort underwent a third endoscopic exam for bleeding and a source was identified in 53.3 % with angioectasias remaining most common (56.3 %). By Fisher's exact and Chi-square testing, only the presence of a bleeding source (p = 0.0034) and use of hemostatic therapy (p = 0.0127) on the index examination were significantly associated with re-bleeding. CONCLUSIONS: GIB is common in patients with LVADs. The diagnostic and therapeutic yield of endoscopy is remains high with repeated interventions. Despite these high yields, a large portion of the cohort requires repeated interventions for recurrent bleeding.
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Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/patologia , Coração Auxiliar/efeitos adversos , Feminino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Disfunção Ventricular Esquerda/terapiaRESUMO
Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite improvements in valve deployment, patients that have undergone TAVR are at high risk for major adverse events following the procedure. Blood cell numbers, platelet function, and biomarkers of systemic inflammation were analyzed in 58 patients undergoing TAVR with the Edward's SAPIEN valve. Following valve deployment, platelet count and agonist-induced platelet activity declined and plasma markers of systemic inflammation (interleukin-6 and S100A8/A9) increased. Baseline platelet activity prior to TAVR correlated with perioperative changes plasma interleukin-6 levels. Moreover, perioperative changes in plasma inflammatory markers predicted the decline in platelet count in the days following the TAVR procedure. Additionally, a significant effect of gender on platelet count following TAVR and was observed. Finally, post-procedural mortality was associated with sustained thrombocytopenia after TAVR. Our findings suggest that TAVR elicits a thromboinflammatory state that may contribute to post-procedural thrombocytopenia. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes.
Assuntos
Trombose/sangue , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de Células Sanguíneas , Calgranulina A/sangue , Calgranulina B/sangue , Feminino , Humanos , Inflamação/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Testes de Função PlaquetáriaRESUMO
The antimicrobial properties of olive leaf extract (OLE) have been well recognized in the Mediterranean traditional medicine. Few studies have investigated the antimicrobial properties of OLE. In this preliminary study, commercial OLE and its major phenolic secondary metabolites were evaluated in vitro for their antimicrobial activities against Escherichia coli and Staphylococcus aureus, both individually and in combination with ampicillin. Besides luteolin 7-O-glucoside, OLE and its major phenolic secondary metabolites were effective against both bacteria, with more activity on S. aureus. In combination with ampicillin, OLE, caffeic acid, verbascoside and oleuropein showed additive effects. Synergistic interaction was observed between ampicillin and hydroxytyrosol. The phenolic composition of OLE and the stability of olive phenols in assay medium were also investigated. While OLE and its phenolic secondary metabolites may not be potent enough as stand-alone antimicrobials, their abilities to boost the activity of co-administered antibiotics constitute an imperative future research area.