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Porcine epidemic diarrhea (PED) virus (PEDV) is a highly contagious virus. PED was first identified in 2008 and has greatly affected the Vietnamese pig production economy. The aim of this study was to investigate the epidemiological and genetic characteristics of PEDV in piglet herds in the Mekong Delta, Vietnam. Diarrheal stool and intestinal samples from 2262 piglets from 191 herds in five provinces were collected to test for the presence of PEDV. Ten PEDV strains were randomly selected for sequencing, and four genes encoding PEDV structural proteins were analyzed. The rates of herds and samples positive for PEDV were 27.23% and 27.72%, respectively. In positive herds, the morbidity and mortality of PEDV-positive piglets were 97.97% and 79.06%, respectively, with most of the infected piglets under 7 days of age. Phylogenetic analysis showed that the 10 PEDV strains from this study clustered with genotype G2 strains from Vietnam and neighboring countries. Many amino acid substitutions were identified in important antigenic regions in the spike protein of the 10 strains when compared to four PEDV vaccine strains. This study provides novel insights into the epidemiology and genetic diversity of circulating PEDV strains, which could facilitate the development of an appropriate and proactive strategy for controlling PED.
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Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Porcinos , Virus de la Diarrea Epidémica Porcina/genética , Filogenia , Vietnam/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/veterinaria , Epidemiología Molecular , Diarrea/epidemiología , Diarrea/veterinaria , Enfermedades de los Porcinos/epidemiologíaRESUMEN
It is well-documented that subway stations exhibit high fine particulate matter (PM2.5) concentrations. Little is known about the potential of river-tunnels to increase PM2.5 concentrations in subways. We hypothesized a "river-tunnel" effect exists: Stations adjacent to poorly ventilated tunnels that travel beneath rivers exhibit higher PM2.5 concentrations than more distant stations. Accordingly, the PM2.5 concentrations were monitored at stations adjacent to and two- and three-stations distant from the river-tunnel. Multivariate linear regression analysis was conducted to disentangle how proximity to a river-tunnel and other factors (e.g., depth) influence concentrations. Stations adjacent to a river-tunnel had 80-130% higher PM2.5 concentrations than more distant stations. Moreover, distance from a river-tunnel was the strongest PM2.5-influencing factor This distance effect was not observed at underground stations adjacent to a river-bridge. The "river-tunnel" effect explains some of the inter-station variability in subway PM2.5 concentrations. These results support the need for improving ventilation systems in subways.
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BACKGROUND: Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-established, there is no clear framework for the communication of the evidence between physicians and patients. For this reason, we developed an evidence-based shared-decision making assistant (SDM-assistant) that presents high-quality evidence from network meta-analysis on the efficacy and side-effect profile of antipsychotics and can be used as a basis for shared-decision making between physicians and patients when selecting antipsychotic medications. METHODS: The planned matched-pair cluster-randomised trial will be conducted in acute psychiatric wards (n = 14 wards planned) and will include adult inpatients with schizophrenia or schizophrenia-like disorders (N = 252 participants planned). On the intervention wards, patients and their treating physicians will use the SDM-assistant, whenever a decision on choosing an antipsychotic is warranted. On the control wards, antipsychotics will be chosen according to treatment-as-usual. The primary outcome will be patients' perceived involvement in the decision-making during the inpatient stay as measured with the SDM-Q-9. We will also assess therapeutic alliance, symptom severity, side-effects, treatment satisfaction, adherence, quality of life, functioning and rehospitalizations as secondary outcomes. Outcomes could be analysed at discharge and at follow-up after three months from discharge. The analysis will be conducted per-protocol using mixed-effects linear regression models for continuous outcomes and logistic regression models using generalised estimating equations for dichotomous outcomes. Barriers and facilitators in the implementation of the intervention will also be examined using a qualitative content analysis. DISCUSSION: This is the first trial to examine a decision assistant specifically designed to facilitate shared-decision making for choosing antipsychotic medications, i.e., SDM-assistant, in acutely ill inpatients with schizophrenia. If the intervention can be successfully implemented, SDM-assistant could advance evidence-based medicine in schizophrenia by putting medical evidence on antipsychotics into the context of patient preferences and values. This could subsequently lead to a higher involvement of the patients in decision-making and better therapy decisions. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00027316 , registration date 26.01.2022).
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Antipsicóticos , Esquizofrenia , Adulto , Aminoacridinas , Antipsicóticos/efectos adversos , Toma de Decisiones , Humanos , Metaanálisis como Asunto , Participación del Paciente , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Esquizofrenia/tratamiento farmacológicoRESUMEN
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic cysts detected by imaging. Cyst size is one of many features evaluated on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS) to help guide IPMN management. Our objective was to determine which imaging modality best predicts pathological cyst size. METHODS: We analyzed records for 57 IPMN cases surgically treated at Moffitt Cancer Center from 2008 to 2016 for whom pre-operative CT, MRI, and EUS IPMN cyst size and post-operative pathological cyst size values were available. Long axis cyst diameter measurements were compared to each other and corresponding pathological cyst measurements using within-subjects ANOVA, Bland-Altman analysis, and linear regression. Consensus measurements were also performed on CT and MRI images. RESULTS: Cyst size measured via CT and MRI overestimated pathological size by 0.33 cm and 0.27 cm, respectively, whereas EUS underestimated pathological size by 0.05 cm and had the narrowest 95% limit of agreement (LOA). Among pathologically-confirmed cysts <3 cm, MRI overestimated pathological size by 0.30 cm (P = 0.049) and had the widest LOA, followed by EUS and CT. Among cysts ≥3 cm, EUS underestimated pathological size by 0.35 cm (P = 0.059) and MRI and CT overestimated pathological size by 0.23 cm and 0.51 cm, respectively. CONCLUSIONS: In this small retrospective study, EUS cyst size measurements correlated best with pathologic specimens compared to CT and MRI, especially for cysts < 3 cm. Larger prospective studies are needed to determine which imaging modalities are best to risk-stratify IPMNs and guide surgical versus. Non-surgical management.
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Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Endosonografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Quiste Pancreático/diagnóstico por imagen , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/patología , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/patología , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos XRESUMEN
Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [68 Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [68 Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [177 Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.
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Antígenos de Superficie/química , Radioisótopos de Galio/química , Glutamato Carboxipeptidasa II/química , Glutamato Carboxipeptidasa II/síntesis química , Lutecio/química , Radioquímica/instrumentación , Radioisótopos/química , Automatización , Técnicas de Química Sintética , Marcaje Isotópico , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
Among the physical attributes of agricultural materials, mass, volume, and sizes have always been important quality parameters. Previous research focused mostly on volume estimation using stereo-based approaches, which rely on manual intervention or require a multiple-cameras set up or multiple-frames captures from different viewing angles to reconstruct the three-dimensional point-cloud information. These approaches are tedious and not suitable for practical machine vision systems. In this work, we only use a single camera mounted on the ceiling of the imaging chamber, which is directly above the fruit/vegetable to capture its top-view, two-dimensional image. We developed a method to estimate the mass/volume of agricultural products with axi-symmetrical shapes such as a carrot or a cucumber. The mass/volume is estimated as the sum of smaller standard blocks, such as chopped pyramids, an elliptical cone, or a conical cone. The computed mass/volume showed good agreement with analytical and experimental results. The weight estimation error is 95% for the case of the carrot and 96.7% for the cucumber. The method proved to be sufficiently accurate, easy to use, and rotationally invariant.
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Agricultura/métodos , Frutas/anatomía & histología , Procesamiento de Imagen Asistido por Computador , Verduras/anatomía & histologíaRESUMEN
OBJECTIVES: To determine the diagnostic accuracy of 68gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with 18F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer. METHODS: Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1-5, > 5) and the inter-reader agreement was calculated (kappa coefficients). RESULTS: Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an "almost perfect" inter-reader agreement (kappa coefficient 0.93). CONCLUSIONS: The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT. KEY POINTS: ⢠PSMA-PET/CT assessed the presence of bone metastases correctly in all 55 patients ⢠PSMA-PET/CT was more advantageous compared to WB-MRI ⢠No difference was found between PSMA-PET/CT and NaF-PET/CT.
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Antígenos de Superficie/farmacología , Neoplasias Óseas/secundario , Radioisótopos de Galio/farmacología , Glutamato Carboxipeptidasa II/farmacología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/patología , Imagen de Cuerpo Entero/métodos , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: Vestibular neuritis is the second cause of vertigo and new imaging protocols using delayed FLAIR with double-dose of gadolinium are proposed for its diagnosis. Our aim is to demonstrate that a single dose of gadolinium is sufficient. METHODS: Thirty-three patients with a unilateral vestibular neuritis are compared to a control group. All patients underwent a FLAIR sequence, 1 hour after intravenous injection of a single dose of gadolinium, on a 1.5 Tesla MRI. Two radiologists analyzed the enhancement intensity of the superior (sup VN) and inferior vestibular nerve (inf VN) and ratios to the signal of the cerebellum were calculated (supVN/C). The statistics were performed using Bayesian analysis. RESULTS: A strong enhancement of the sup VN was observed on the pathological side in 85% of patients with vestibular neuritis. The average signal intensity of the pathological sup VN (139 units ± 44) was more than two times the average intensity in the control group (58.5 units ± 5). The average ratios supVN/C were significantly different between the pathological side in vestibular neuritis (2.43 units ± 0.63) and the control group [1.16 ± 0.14 (Pr(diff > 0) = 1)]. A delayed enhancement > 71.5 units had a sensitivity of 96% and a specificity of 100% for the diagnosis of superior vestibular neuritis. CONCLUSION: A delayed FLAIR sequence, acquired 1 hour after a single dose of gadolinium injection, is a useful method for the diagnosis of vestibular neuritis. An enhancement of the sup VN > 71.5 units was in favor of the diagnosis.
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Gadolinio DTPA/administración & dosificación , Imagen por Resonancia Magnética/métodos , Nervio Vestibular/diagnóstico por imagen , Neuronitis Vestibular/diagnóstico , Adulto , Anciano , Teorema de Bayes , Estudios de Casos y Controles , Medios de Contraste , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Vértigo/etiología , Pruebas de Función Vestibular , Nervio Vestibular/patología , Neuronitis Vestibular/diagnóstico por imagenRESUMEN
In the present study, the mechanism of action and molecular basis for the activity of the first class of selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rodent ortholog GLAST are elucidated. The previously reported specificity of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to the EAAT4 and EAAT5 subtypes as well. Interestingly, brief exposure to UCPH-101 induces a long-lasting inactive state of EAAT1, whereas the inhibition exerted by closely related analogs is substantially more reversible in nature. In agreement with this, the kinetic properties of UCPH-101 unblocking of the transporter are considerably slower than those of UCPH-102. UCPH-101 exhibits noncompetitive inhibition of EAAT1, and its binding site in GLAST has been delineated in an elaborate mutagenesis study. Substitutions of several residues in TM3, TM4c, and TM7a of GLAST have detrimental effects on the inhibitory potency and/or efficacy of UCPH-101 while not affecting the pharmacological properties of (S)-glutamate or the competitive EAAT inhibitor TBOA significantly. Hence, UCPH-101 is proposed to target a predominantly hydrophobic crevice in the "trimerization domain" of the GLAST monomer, and the inhibitor is demonstrated to inhibit the uptake through the monomer that it binds to exclusively and not to affect substrate translocation through the other monomers in the GLAST trimer. The allosteric mode of UCPH-101 inhibition underlines the functional importance of the trimerization domain of the EAAT and demonstrates the feasibility of modulating transporter function through ligand binding to regions distant from its "transport domain."
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Regulación Alostérica/efectos de los fármacos , Benzopiranos/farmacología , Transportador 1 de Aminoácidos Excitadores/antagonistas & inhibidores , Animales , Transporte Biológico/fisiología , Células Cultivadas , Transportador 1 de Aminoácidos Excitadores/genética , Transportador 1 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 3 de Aminoácidos Excitadores/genética , Transportador 3 de Aminoácidos Excitadores/metabolismo , Transportador 4 de Aminoácidos Excitadores/genética , Transportador 4 de Aminoácidos Excitadores/metabolismo , Humanos , RatasRESUMEN
The membrane bound enzyme monoamine oxidase exist in two splice variants designated A and B (MAO-A and MAO-B) and are key players in the oxidative metabolism of monoamines in mammalians. Despite their importance and being a prevalent target for the development of inhibitors as drugs, no systematic study of substrate specificity has been reported. In this study we present a systematic study of the MAO-A and MAO-B substrate specificity profile by probing two series of phenethylamine analogs. Km and kcat values were determined for four N-alkyl analogs 2-5 and four aryl halide analogs 6-9 at MAO-A and MAO-B. A following in silico study disclosed a new adjacent compartment to the MAO-B substrate pocket defined by amino acids Tyr188, Tyr435, Tyr398, Thr399, Cys172 and Gly434. This new insight is important for the understanding of the substrate specificity of the MAO-B enzyme and will be relevant for future drug design within the field of monoamines.
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Inhibidores de la Monoaminooxidasa/química , Monoaminooxidasa/química , Fenetilaminas/química , Humanos , Cinética , Kinuramina/química , Modelos Moleculares , Inhibidores de la Monoaminooxidasa/síntesis química , Fenetilaminas/síntesis química , Proteínas Recombinantes/química , Soluciones , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder with increasing global prevalence and accounts for over half of all dementia cases. Early diagnosis is paramount for not only the management of the disease, but also for the development of new AD treatments. The current golden standard for diagnosis is performed by positron emission tomography (PET) scans with the tracer [11C]Pittsburg Compound B ([11C]PiB), which targets amyloid beta protein (Aß) that builds up as plaques in the brain of AD patients. The increasing demand for AD diagnostics is in turn expected to drive an increase in [11C]PiB-PET scans and the setup of new [11C]PiB production lines at PET centers globally. Here, we present the [11C]PiB production setups, experiences, and use from four Danish PET facilities and discuss the challenges and potential pitfalls of [11C]PiB production. We report on the [11C]PiB production performed with the 6-OH-BTA-0 precursor dissolved in either dry acetone or 2-butanone and by using either [11C]CO2 or [11C]CH4 as 11C- precursors on three different commercial synthesis modules: TracerLab FX C Pro, ScanSys, or TracerMaker. It was found that the [11C]CO2 method gives the highest radioactive yield (1.5 to 3.2 GBq vs. 0.8 ± 0.3 GBq), while the highest molar activity (98.0 ± 61.4 GBq/µmol vs. 21.2 to 95.6 GBq/µmol) was achieved using [11C]CH4. [11C]PiB production with [11C]CO2 on a TracerLab FX C Pro offered the most desirable results, with the highest yield of 3.17 ± 1.20 GBq and good molar activity of 95.6 ± 44.2 GBq/µmol. Moreover, all reported methods produced [11C]PiB in quantities suitable for clinical applications, thus providing a foundation for other PET facilities seeking to establish their own [11C]PiB production.
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BACKGROUND: Pyrotechnic displays often lead to significant increases in poor air quality. The widespread environmental fate-involving air, water, and spatial-temporal analyses-of fireworks-produced pollutants has seldom been investigated. OBJECTIVE: This study examined the environmental fate of pollutants from the largest fireworks event in the U.S.: Macy's Fourth of July Fireworks show in New York City (NYC). METHODS: Real-time PM2.5 and gravimetric PM2.5 and PM10 were collected at locations along the East River of NYC. Airborne particles were assayed for trace elements (X-ray fluorescence) and organic and elemental carbon (OC/EC). River water samples were evaluated by ICP-MS for heavy-metal water contamination. Spatial-temporal analyses were created using PM2.5 concentrations reported by both EPA and PurpleAir monitoring networks for NYC and 5 other major metropolitan areas. RESULTS: The fireworks event resulted in large increases in PM2.5 mass concentrations at the river-adjacent sampling locations. While background control PM2.5 was 10-15 µg/m3, peak real-time PM2.5 levels exceeded 3000 µg/m3 at one site and 1000 µg/m3 at two other locations. The integrated gravimetric PM2.5 and PM10 concentrations during the fireworks event ranged from 162 to 240 µg/m3 and 252 to 589 µg/m3, respectively. Zn, Pb, Sb, and Cu more than doubled in river water samples taken after the event, while S, K, Ba, Cu, Mg, Fe, Sr, Ti, and Zn increased in airborne PM2.5 from the fireworks. Data from hyperlocal monitoring networks for NYC and other metropolitan areas yielded similar, but generally smaller, increases in PM2.5 levels. IMPACT: Fireworks shows have been associated with environmental contamination. This comprehensive analysis considers the fate of pollutants from the largest annual U.S. pyrotechnic show through air, water, and hyperlocal temporal characterization.
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BACKGROUND: While multiple cyst features are evaluated for stratifying pancreatic intraductal papillary mucinous neoplasms (IPMN), cyst size is an important factor that can influence treatment strategies. When magnetic resonance imaging (MRI) is used to evaluate IPMNs, no universally accepted sequence provides optimal size measurements. T2-weighted coronal/axial have been suggested as primary measurement sequences; however, it remains unknown how well these and maximum all-sequence diameter measurements correlate with pathology size. This study aims to compare agreement and bias between IPMN long-axis measurements on seven commonly obtained MRI sequences with pathologic size measurements. METHODS: This retrospective cohort included surgically resected IPMN cases with preoperative MRI exams. Long-axis diameter tumor measurements and the presence of worrisome features and/orhigh-risk stigmata were noted on all seven MRI sequences. MRI size and pathology agreement and MRI inter-observer agreement involved concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC), respectively. The presence of worrisome features and high-risk stigmata were compared to the tumor grade using kappa analysis. The Bland-Altman analysis assessed the systematic bias between MRI-size and pathology. RESULTS: In 52 patients (age 68 ± 13 years, 22 males), MRI sequences produced mean long-axis tumor measurements from 2.45-2.65 cm. The maximum MRI lesion size had a strong agreement with pathology (CCC = 0.82 (95% CI: 0.71-0.89)). The maximum IPMN size was typically observed on the axial T1 arterial post-contrast and MRCP coronal series and overestimated size versus pathology with bias +0.34 cm. The radiologist interobserver agreement reached ICCs 0.74 to 0.91 on the MRI sequences. CONCLUSION: The maximum MRI IPMN size strongly correlated with but tended to overestimate the length compared to the pathology, potentially related to formalin tissue shrinkage during tissue processing.
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INTRODUCTION AND PATIENT CONCERNS: We report on a 45-year-old woman who has a ventriculoperitoneal shunt (VPS), experienced drowsy mental status, with hypesthesia and hemiplegia on the left side. Ten days ago she underwent laparoscopic cholecystectomy (LC). Computed tomography revealed tension pneumocephalus, with severe compression on the right side of the brain. INTERVENTIONS AND DIAGNOSIS: She underwent 2 surgeries, the first surgery was to place a subdural drainage catheter, however, the pneumocephalus relapsed after withdrawing the catheter, and the later surgery was to replace the new VPS. OUTCOMES: After replacing the VPS, the patient recovers completely after 10 weeks of follow-up. CONCLUSION: To our knowledge, this is the first report of LC-induced tension pneumocephalus in a patient with VPS. The purpose of this study is to share our experience, with the hypothesized mechanism being the retrograde air through the VPS valve because of high abdominal pressurization. We recommend noting the existence of the VPS when the LC or any abdominal laparoscopy is performed. The VPS should be clamped during any laparoscopic procedure until complete depressurization. Furthermore, all patients with VPS who have neurological deterioration after abdominal laparoscopy should be treated as having the diagnosis of a tension pneumocephalus. These patients need emergency surgery to replace VPS and set the valve for high-pressure, which can result in a quick and complete recovery.
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Colecistectomía Laparoscópica , Hidrocefalia , Laparoscopía , Neumocéfalo , Femenino , Humanos , Persona de Mediana Edad , Colecistectomía Laparoscópica/efectos adversos , Cabeza/cirugía , Hidrocefalia/cirugía , Laparoscopía/métodos , Neumocéfalo/diagnóstico por imagen , Neumocéfalo/etiología , Derivación VentriculoperitonealRESUMEN
RATIONALE AND PATIENT CONCERNS: We report on a 67-year-old woman who experienced drowsy mental status, facial numbness, and hearing loss on the right side; the symptom gradually worsened over the last 4 years. Brain magnetic resonance imaging revealed a 4.8 × 1.8 × 2.6 cm lesion located in the right cerebellopontine angle. INTERVENTIONS: She underwent surgery with the retrosigmoid suboccipital approach and support from the digital robotic exoscope Synaptive Modus V system. To the best of our knowledge, this is the first reported case that used the robotic exoscope system in Vietnam, and also in Asia. DIAGNOSIS: We performed radical resection of the tumor, the surgery position and the pathology result concluded the diagnosis was trigeminal schwannoma. OUTCOMES: After 30 months of follow-up, she fully recovered and the magnetic resonance imaging showed radical resection of the tumor. LESSONS: The aim of this study is to share our experience with the robotic exoscope system, which can improve optical field and image resolution, hence creating an opportunity for surgery that otherwise is impossible. The application of this robotic exoscope system is a breakthrough in neurosurgery in developing countries, such as Vietnam.
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Neoplasias de los Nervios Craneales , Neurilemoma , Procedimientos Quirúrgicos Robotizados , Femenino , Humanos , Anciano , Ángulo Pontocerebeloso/cirugía , Ángulo Pontocerebeloso/patología , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Neurilemoma/patología , Neoplasias de los Nervios Craneales/patología , Procedimientos Neuroquirúrgicos/métodosRESUMEN
The excitatory amino acid transporters (EAATs) play a pivotal role in regulating the synaptic concentration of glutamate in the mammalian central nervous system. To date, five different subtypes have been identified, named EAAT15 in humans (and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5, respectively, in rodents). Recently, we have published and presented a structure-activity relationship (SAR) study of a novel class of selective inhibitors of EAAT1 (and GLAST), with the analogs UCPH-101 (IC(50)=0.66µM) and UCPH-102 (IC(50)=0.43µM) being the most potent inhibitors in the series. In this paper, we present the design, synthesis and pharmacological evaluation of six coumarin-based fluorescent analogs of UCPH-101/102 as subtype-selective inhibitors at EAAT1. Analogs 1114 failed to inhibit EAAT1 function (IC(50) values >300µM), whereas analogs 15 and UCPH-102F inhibited EAAT1 with IC(50) values in the medium micromolar range (17µM and 14µM, respectively). Under physiological pH no fluorescence was observed for analog 15, while a bright blue fluorescence emission was observed for analog UCPH-102F. Regrettably, under confocal laser scanning microscopy selective visualization of expression of EAAT1 over EAAT3 was not possible due to nonspecific binding of UCPH-102F.
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Benzopiranos/química , Benzopiranos/farmacología , Cumarinas/química , Cumarinas/farmacología , Transportador 1 de Aminoácidos Excitadores/antagonistas & inhibidores , Benzopiranos/síntesis química , Cumarinas/síntesis química , Diseño de Fármacos , Transportador 1 de Aminoácidos Excitadores/metabolismo , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Células HEK293 , Humanos , Concentración 50 Inhibidora , Relación Estructura-ActividadRESUMEN
BACKGROUND AND OBJECTIVE: Medical image classification is often challenging for two reasons: a lack of labelled examples due to expensive and time-consuming annotation protocols, and imbalanced class labels due to the relative scarcity of disease-positive individuals in the wider population. Semi-supervised learning methods exist for dealing with a lack of labels, but they generally do not address the problem of class imbalance. Hence, the purpose of this study is to explore a new approach to perturbation-based semi-supervised learning which tackles the problem of applying semi-supervised learning to medical image classification with imbalanced training data. METHODS: In this study we propose Adaptive Blended Consistency Loss (ABCL), a simple yet effective drop-in replacement for consistency loss in perturbation-based semi-supervised learning methods. ABCL counteracts data skew by adaptively mixing the target class distribution of the consistency loss in accordance with class frequency. Our proposed method is evaluated and compared with existing methods on two different imbalanced medical image classification datasets. An ablation study is also provided to analyse the properties and effectiveness of our proposed method. RESULTS: Our experiments with ABCL reveal improvements to unweighted average recall (UAR) when compared with existing consistency losses that are not designed to counteract class imbalance and other existing methods. Our proposed ABCL method is able to improve the performance of the baseline consistency loss approach from 0.59 to 0.67 UAR and outperforms methods that address the class imbalance problem for labelled data (between 0.51 and 0.59 UAR) and for unlabelled data (0.61 UAR) on the imbalanced skin cancer dataset. On the imbalanced retinal fundus glaucoma dataset, ABCL (combined with Weighted Cross Entropy loss) achieves 0.67 UAR, which is an improvement over the best existing approach (0.57 UAR). CONCLUSIONS: Overall the results show the effectiveness of ABCL to alleviate the class imbalance problem for semi-supervised classification for medical images.
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Proyectos de Investigación , Aprendizaje Automático Supervisado , Entropía , HumanosRESUMEN
Epileptic seizure is a neurological condition caused by short and unexpectedly occurring electrical disruptions in the brain. It is estimated that roughly 60 million individuals worldwide have had an epileptic seizure. Experiencing an epileptic seizure can have serious consequences for the patient. Automatic seizure detection on electroencephalogram (EEG) recordings is essential due to the irregular and unpredictable nature of seizures. By thoroughly analyzing EEG records, neurophysiologists can discover important information and patterns, and proper and timely treatments can be provided for the patients. This research presents a novel machine learning-based approach for detecting epileptic seizures in EEG signals. A public EEG dataset from the University of Bonn was used to validate the approach. Meaningful statistical features were extracted from the original data using discrete wavelet transform analysis, then the relevant features were selected using feature selection based on the binary particle swarm optimizer. This facilitated the reduction of 75% data dimensionality and 47% computational time, which eventually sped up the classification process. After having been selected, relevant features were used to train different machine learning models, then hyperparameter optimization was utilized to further enhance the models' performance. The results achieved up to 98.4% accuracy and showed that the proposed method was very effective and practical in detecting seizure presence in EEG signals. In clinical applications, this method could help relieve the suffering of epilepsy patients and alleviate the workload of neurologists.
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Parkinson's Disease (PD) is a brain disorder that causes uncontrollable movements. According to estimation, roughly ten million individuals worldwide have had or are developing PD. This disorder can have severe consequences that affect the patient's daily life. Therefore, several previous works have worked on PD detection. Automatic Parkinson's Disease detection in voice recordings can be an innovation compared to other costly methods of ruling out examinations since the nature of this disease is unpredictable and non-curable. Analyzing the collected vocal records will detect essential patterns, and timely recommendations on appropriate treatments will be extremely helpful. This research proposed a machine learning-based approach for classifying healthy people from people with the disease utilizing Grey Wolf Optimization (GWO) for feature selection, along with Light Gradient Boosted Machine (LGBM) to optimize the model performance. The proposed method shows highly competitive results and has the ability to be developed further and implemented in a real-world setting.
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BACKGROUND: The radiofluorinated levodopa analogue 6-[18F]F-L-DOPA (3,4-dihydroxy-6-18F-L-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [18F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site. METHODS: Data from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed. RESULTS: The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants. CONCLUSION: For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.