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1.
Front Oncol ; 13: 1196414, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37546399

RESUMEN

Background: Recent developments in artificial intelligence suggest that radiomics may represent a promising non-invasive biomarker to predict response to immune checkpoint inhibitors (ICIs). Nevertheless, validation of radiomics algorithms in independent cohorts remains a challenge due to variations in image acquisition and reconstruction. Using radiomics, we investigated the importance of scan normalization as part of a broader machine learning framework to enable model external generalizability to predict ICI response in non-small cell lung cancer (NSCLC) patients across different centers. Methods: Radiomics features were extracted and compared from 642 advanced NSCLC patients on pre-ICI scans using established open-source PyRadiomics and a proprietary DeepRadiomics deep learning technology. The population was separated into two groups: a discovery cohort of 512 NSCLC patients from three academic centers and a validation cohort that included 130 NSCLC patients from a fourth center. We harmonized images to account for variations in reconstruction kernel, slice thicknesses, and device manufacturers. Multivariable models, evaluated using cross-validation, were used to estimate the predictive value of clinical variables, PD-L1 expression, and PyRadiomics or DeepRadiomics for progression-free survival at 6 months (PFS-6). Results: The best prognostic factor for PFS-6, excluding radiomics features, was obtained with the combination of Clinical + PD-L1 expression (AUC = 0.66 in the discovery and 0.62 in the validation cohort). Without image harmonization, combining Clinical + PyRadiomics or DeepRadiomics delivered an AUC = 0.69 and 0.69, respectively, in the discovery cohort, but dropped to 0.57 and 0.52, in the validation cohort. This lack of generalizability was consistent with observations in principal component analysis clustered by CT scan parameters. Subsequently, image harmonization eliminated these clusters. The combination of Clinical + DeepRadiomics reached an AUC = 0.67 and 0.63 in the discovery and validation cohort, respectively. Conversely, the combination of Clinical + PyRadiomics failed generalizability validations, with AUC = 0.66 and 0.59. Conclusion: We demonstrated that a risk prediction model combining Clinical + DeepRadiomics was generalizable following CT scan harmonization and machine learning generalization methods. These results had similar performances to routine oncology practice using Clinical + PD-L1. This study supports the strong potential of radiomics as a future non-invasive strategy to predict ICI response in advanced NSCLC.

2.
Sci Rep ; 13(1): 10235, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37353545

RESUMEN

Detecting Escherichia coli is essential in biomedical, environmental, and food safety applications. In this paper, we have developed a simple, rapid, sensitive, and selective E. coli DNA sensor based on the novel hybrid-type [Formula: see text] and [Formula: see text] nanosheets. The sensor uses the absorbance measurement to distinguish among the DNA of E. coli, Vibrio proteolyticus, and Bacillus subtilis when implemented in conjunction with [Formula: see text]-probes. Our experiments showed that the absorbance increased when sensors detected E. coli DNA, whereas it decreased when sensors detected V. proteolyticus and B. subtilis DNA. To the best of authors' knowledge, there are no reports using the novel hybrid-[Formula: see text] and [Formula: see text] materials for differentiating three types of DNA using cost-effective and rapid absorbance measurements. In addition, the label-free E. coli DNA biosensor exhibited a linear response in the range of 0 fM to 11.65 fM with a limit of detection of 2 fM. The effect of [Formula: see text]-probes on our sensors' working performance is also investigated. Our results will facilitate further research in pathogen detection applications, which have not been fully developed yet.


Asunto(s)
Técnicas Biosensibles , Escherichia coli , Escherichia coli/genética , Bacillus subtilis
3.
Physiother Can ; 75(1): 22-28, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37250725

RESUMEN

Purpose: To determine whether there was an association between self-reported preoperative exercise and postoperative outcomes after lumbar fusion spinal surgery. Method: We performed a retrospective multivariable analysis of the prospective Canadian Spine Outcomes and Research Network (CSORN) database of 2,203 patients who had elective single-level lumbar fusion spinal surgeries. We compared adverse events and hospital length of stay between patients who reported regular exercise (twice or more per week) prior to surgery ("Regular Exercise") to those exercising infrequently (once or less per week) ("Infrequent Exercise") or those who did no exercise ("No Exercise"). For all final analyses, we compared the Regular Exercise group to the combined Infrequent Exercise or No Exercise group. Results: After making adjustments for known confounding factors, we demonstrated that patients in the Regular Exercise group had fewer adverse events (adjusted odds ratio 0.72; 95% CI: 0.57, 0.91; p = 0.006) and significantly shorter lengths of stay (adjusted mean 2.2 vs. 2.5 d, p = 0.029) than the combined Infrequent Exercise or No Exercise group. Conclusions: Patients who exercised regularly twice or more per week prior to surgery had fewer postoperative adverse events and significantly shorter hospital lengths of stay compared to patients that exercised infrequently or did no exercise. Further study is required to determine effectiveness of a targeted prehabilitation programme.


Objectif : déterminer s'il y avait une association entre les exercices préopératoires autodéclarés et les résultats postopératoires après une chirurgie de fusion lombaire. Méthodologie : analyse multivariable rétrospective de la base de données prospective Canadian Spine Outcomes and Research Network (CSORN) composée de 2 203 patients qui avaient subi une chirurgie de fusion lombaire univertébrale non urgente. Les chercheurs ont comparé les événements indésirables et la durée du séjour hospitalier entre les patients qui déclaraient faire de l'exercice régulier (au moins deux fois par semaine) avant l'opération (« exercice régulier ¼) à ceux qui n'en faisaient pas souvent (une fois ou moins par semaine; « exercice peu fréquent ¼) et qui n'en faisaient pas du tout (« absence d'exercice ¼). Pour toutes les analyses définitives, ils ont comparé le groupe qui faisait de l'exercice régulier aux groupes combinés d'exercice peu fréquent et d'absence d'exercice. Résultats : après correction pour tenir compte des facteurs confusionnels connus, les chercheurs ont démontré que les patients du groupe faisant de l'exercice régulier présentaient moins d'événements indésirables (rapport de cotes rajusté 0,72; IC à 95 % : 0,57, 0,91; p = 0,006) et leur séjour à l'hôpital était significativement plus court (moyenne corrigée 2,2 jours par rapport à 2,5 jours, p = 0,029) que dans le groupe combiné d'exercice peu fréquent et d'absence d'exercice. Conclusions : les patients qui faisaient de l'exercice régulièrement au moins deux fois par semaine avant l'opération présentaient moins d'événements indésirables après l'opération et étaient hospitalisés beaucoup moins longtemps que ceux qui ne faisaient pas beaucoup d'exercice ou n'en faisaient pas du tout. Il faudra réaliser d'autres études pour déterminer l'efficacité d'un programme de préréadaptation ciblé.

4.
Sci Rep ; 13(1): 4380, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36928671

RESUMEN

Groundwater serves as an important resource for people in the Mekong Delta, but its quality has been continuously declined from human activities. Current status of the groundwater quality needs to be evaluated for sustainable groundwater resource management. This study aimed to evaluate the groundwater quality for drinking purposes in the Mekong Delta, Vietnam, using multivariate statistical methods and integrated-weight water quality index. Data comprised 8 water quality parameters (pH, total hardness, nitrate (NO3-), iron (Fe), lead (Pb), mercury (Hg), arsenic (As), and coliforms) obtained from 64 observation wells in An Giang province, Dong Thap province, and Can Tho city, were analyzed by cluster analysis (CA), principal component analysis (PCA), and integrated-weight water quality index (IWQI). The results indicated that most parameters were within standards while excessive hardness and Fe contamination were found in some regions. More than 80% of samples were detected with serious coliform contamination. The CA results revealed that groundwater quality heavily depend on geological locations with 4 clusters of the sampling locations. Three principal components obtained from PCA could explain 77.2% of the groundwater quality variation. The IWQI values ranging from 4 to 2761 classified groundwater quality as excellent (53.1%), good (25%), poor (9.4%), very poor (4.7%), and undrinkable (7.8%), which were associated with coliform contamination. These findings have provided insights into the groundwater quality status in the region, which can benefit in developing a water protection strategy.


Asunto(s)
Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , Humanos , Monitoreo del Ambiente/métodos , Vietnam , Contaminantes Químicos del Agua/análisis , Agua Subterránea/análisis , Calidad del Agua , Agua Potable/análisis
5.
Sensors (Basel) ; 23(5)2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36905045

RESUMEN

The primary goal of glucose sensing at the point of care is to identify glucose concentrations within the diabetes range. However, lower glucose levels also pose a severe health risk. In this paper, we propose quick, simple, and reliable glucose sensors based on the absorption and photoluminescence spectra of chitosan-capped ZnS-doped Mn nanomaterials in the range of 0.125 to 0.636 mM glucose corresponding to 2.3 mg/dL to 11.4 mg/dL. The detection limit was 0.125 mM (or 2.3 mg/dL), much lower than the hypoglycemia level of 70 mg/dL (or 3.9 mM). Chitosan-capped ZnS-doped Mn nanomaterials retain their optical properties while improving sensor stability. This study reports for the first time how the sensors' efficacy was affected by chitosan content from 0.75 to 1.5 wt.%. The results showed that 1 %wt chitosan-capped ZnS-doped Mn is the most-sensitive, -selective, and -stable material. We also put the biosensor through its paces with glucose in phosphate-buffered saline. In the same range of 0.125 to 0.636 mM, the sensors-based chitosan-coated ZnS-doped Mn had a better sensitivity than the working water environment.


Asunto(s)
Quitosano , Nanoestructuras , Puntos Cuánticos , Sulfuros , Glucosa
6.
Radiol Case Rep ; 18(4): 1530-1535, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36815146

RESUMEN

Isolated major aortopulmonary collateral artery (MAPCA), in the absence of evidence of structural heart disease, is a very rare observation. This anomaly usually appears in preterm newborns. In the majority of babies, isolated MAPCAs cause no symptoms and regress spontaneously after birth and their conservative management is usually sufficient. We report a case of an asymptomatic full-term 5-month-old infant presenting with heart murmur as the only sign during clinical evaluation. Echocardiography revealed a dilated left ventricle, with no pulmonary hypertension. Computed tomography angiogram showed a large MAPCA arising from the descending thoracic aorta and supplying blood to the left lower lobe. The condition was managed successfully by percutaneous obliteration with Amplatzer vascular plugs. Isolated MAPCA is usually a benign anomaly, presenting no clinical finding and requiring no specific treatment. However, in a small minority of infants, this congenital disorder may progress, with detrimental impacts on cardiac structure before clinical symptoms appear. Early intervention may be required to prevent irreversible sequelae.

7.
Can J Anaesth ; 69(12): 1556-1561, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36198993

RESUMEN

PURPOSE: The prone position can lead to anatomical compression of the thoracic cavity resulting in reduced cardiac output, especially in the context of chest wall deformities commonly present in patients with scoliosis. There are no protocols for using transesophageal echocardiography (TEE) to optimize prone positioning and for safe use of TEE during cases requiring neuromonitoring. CLINICAL FEATURES: We present a case of a 23-yr-old male with Cornelia de Lange syndrome undergoing elective posterior spinal fusion for syndromic scoliosis who developed severe refractory hypotension and cardiac arrest in the prone position. After hemodynamic stabilization in the intensive care unit, the patient returned to the operating room on postoperative day 2 for completion of his spinal fusion. Transesophageal echocardiography determined the optimal position of longitudinal bolster placements associated with minimal left ventricular compression in the supine position. The patient was then proned and intraoperative hemodynamics during the second surgery remained stable. Owing to the special considerations of using TEE in the prone position with neuromonitoring, we describe technical aspects to consider to protect the equipment and patient. CONCLUSION: Patients with compliant chest walls or thoracic deformities are at risk of hemodynamic instability in the prone position. Intraoperative TEE can be used in the supine patient prior to proning to determine optimal longitudinal bolster positioning to minimize cardiac compression. Transesophageal echocardiography used during spine surgery in the prone position with neuromonitoring and motor-evoked potentials requires special considerations for patient safety.


RéSUMé: OBJECTIF: La position ventrale peut entraîner une compression anatomique de la cavité thoracique provoquant une réduction du débit cardiaque, en particulier dans le contexte de déformations de la paroi thoracique, fréquentes chez les patients atteints de scoliose. Il n'existe aucun protocole guidant l'utilisation de l'échocardiographie transœsophagienne (ETO) pour optimiser le positionnement ventral et pour favoriser l'utilisation sécuritaire de l'ETO dans les cas nécessitant un neuro-monitorage. CARACTéRISTIQUES CLINIQUES: Nous présentons le cas d'un homme de 23 ans atteint d'un syndrome de Cornelia de Lange bénéficiant d'une fusion spinale postérieure non urgente pour traiter une scoliose syndromique; le patient a manifesté une hypotension réfractaire sévère et un arrêt cardiaque en position ventrale. Après stabilisation hémodynamique à l'unité de soins intensifs, le patient est retourné en salle d'opération au jour postopératoire 2 pour terminer sa fusion spinale. L'échocardiographie transœsophagienne a permis de déterminer la position optimale des traversins longitudinaux qui était associée à une compression ventriculaire gauche minimale en décubitus dorsal. Le patient a ensuite été positionné sur le ventre, et les valeurs hémodynamiques peropératoires sont restées stables au cours de la deuxième chirurgie. En raison des considérations particulières de l'utilisation de l'ETO en position ventrale avec neuro-monitorage, nous décrivons les aspects techniques à prendre en compte pour protéger l'équipement et le patient. CONCLUSION: Les patients présentant des parois thoraciques compliantes ou des déformations thoraciques sont à risque d'instabilité hémodynamique en position ventrale. L'ETO peropératoire peut être utilisée chez le patient en décubitus dorsal avant le positionnement ventral pour déterminer le positionnement optimal des traversins longitudinaux afin de minimiser la compression cardiaque. L'utilisation de l'échocardiographie transœsophagienne lors d'une chirurgie du rachis en position ventrale avec neuro-monitorage et potentiels évoqués moteurs nécessite des considérations particulières en ce qui a trait à la sécurité des patients.


Asunto(s)
Ecocardiografía Transesofágica , Escoliosis , Humanos , Masculino , Escoliosis/cirugía , Posición Prona/fisiología , Hemodinámica/fisiología , Posicionamiento del Paciente
8.
Clin Nurse Spec ; 36(6): 298-308, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36279491

RESUMEN

PURPOSE/AIMS: To gain insights in how women use technology to address health information needs during the prenatal and postpartum time frame. DESIGN: An exploratory qualitative study recruited pregnant and recent postpartum women to share their perspectives on information they needed and how they obtained it. METHODS: Women who were pregnant or <90 days postpartum (n = 26) were recruited via social media and invited to share their experiences. Design thinking methodology was used to develop questions to understand information needs in the perinatal period as well as in context of the COVID-19 pandemic. Verbatim transcripts were coded by the research team according to Braun and Clarke's reflexive thematic analysis. RESULTS: Five themes explain the experience of seeking information to support the perinatal period. Women explained the need for the following: (1) information and relationships are inseparable, (2) current practices leave needs unmet, (3) the pandemic exposes vulnerability in prenatal care, (4) left to figure it out alone, and (5) bridging the gap through technology. CONCLUSIONS: Aggregated findings suggest how usual care can be modified to improve support for women through personalized care, improved information support, and use of technology. The study findings inform innovative strategies using current technologies to improve health promotion in a dynamic health environment.


Asunto(s)
COVID-19 , Pandemias , Embarazo , Femenino , Humanos , COVID-19/epidemiología , Periodo Posparto , Investigación Cualitativa
9.
Environ Monit Assess ; 194(11): 844, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36175696

RESUMEN

This study assessed the surface water quality in Can Tho city, Vietnam, using a combination of water quality, pollution indices, and multivariate statistical methods. Surface water samples were collected at 38 locations with a frequency of 4 times in 2020 (March, June, September, and December) and at the time of high and low tides to analyze for 18 indicators. Results showed that surface water in Can Tho city was contaminated with organic matters and microorganisms. Parameters of pH, turbidity, total suspended solids (TSS), biochemical oxygen demand (BOD), chemical oxygen demand (COD), N-NH4+, and N-NO3- are significantly increased with low tide. Comprehensive pollution index indicated mild to moderately polluted water in March, June, and September and moderately to severely polluted water in December. Organic pollution index revealed that surface water quality in all locations was polluted with organic matters during the study period especially in March and December. The water quality index also indicated that water quality in December was mostly classified as moderate and bad. The principal component analysis indicated that surface water quality could be affected by five main sources that explain 64.40% of the total variation. This significantly caused the fluctuation of pH, temperature, turbidity, TSS, DO, BOD, COD, N-NH4+, P-PO43-, Fe, and As, which should all be the focus for future monitoring. Surface water management in Can Tho city should also emphasize on the wastewater from urbanization and agriculture, which has been recognized by the analysis to have highest contribution to organic, nutrient, and microbial pollutants in the water bodies.


Asunto(s)
Contaminantes Ambientales , Calidad del Agua , Monitoreo del Ambiente , Oxígeno , Vietnam , Aguas Residuales
10.
Acta Crystallogr D Struct Biol ; 78(Pt 3): 268-277, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35234141

RESUMEN

One often observes small but measurable differences in the diffraction data measured from different crystals of a single protein. These differences might reflect structural differences in the protein and may reveal the natural dynamism of the molecule in solution. Partitioning these mixed-state data into single-state clusters is a critical step that could extract information about the dynamic behavior of proteins from hundreds or thousands of single-crystal data sets. Mixed-state data can be obtained deliberately (through intentional perturbation) or inadvertently (while attempting to measure highly redundant single-crystal data). To the extent that different states adopt different molecular structures, one expects to observe differences in the crystals; each of the polystates will create a polymorph of the crystals. After mixed-state diffraction data have been measured, deliberately or inadvertently, the challenge is to sort the data into clusters that may represent relevant biological polystates. Here, this problem is addressed using a simple multi-factor clustering approach that classifies each data set using independent observables, thereby assigning each data set to the correct location in conformational space. This procedure is illustrated using two independent observables, unit-cell parameters and intensities, to cluster mixed-state data from chymotrypsinogen (ChTg) crystals. It is observed that the data populate an arc of the reaction trajectory as ChTg is converted into chymotrypsin.


Asunto(s)
Proteínas , Modelos Moleculares , Conformación Molecular , Estructura Molecular
12.
Am J Obstet Gynecol ; 226(6): 833.e1-833.e20, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34863697

RESUMEN

BACKGROUND: Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy. OBJECTIVE: This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk. STUDY DESIGN: Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery. RESULTS: High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia. CONCLUSION: High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.


Asunto(s)
Trastornos de Somnolencia Excesiva , Preeclampsia , Síndromes de la Apnea del Sueño , Rigidez Vascular , Presión Sanguínea/fisiología , Femenino , Humanos , Preeclampsia/epidemiología , Embarazo , Embarazo de Alto Riesgo , Estudios Prospectivos , Análisis de la Onda del Pulso , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/epidemiología , Somnolencia , Rigidez Vascular/fisiología
13.
Sensors (Basel) ; 23(1)2022 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-36616780

RESUMEN

Spine movement is a daily activity that can indicate health status changes, including low back pain (LBP) problems. Repetitious and continuous movement on the spine and incorrect postures during daily functional activities may lead to the potential development and persistence of LBP problems. Therefore, monitoring of posture and movement is essential when designing LBP interventions. Typically, LBP diagnosis is facilitated by monitoring upper body posture and movement impairments, particularly during functional activities using body motion sensors. This study presents a fully wireless multi-sensor cluster system to monitor spine movements. The study suggests an attempt to develop a new method to monitor the lumbopelvic movements of interest selectively. In addition, the research employs a custom-designed robotic lumbar spine simulator to generate the ideal lumbopelvic posture and movements for reference sensor data. The mechanical motion templates provide an automated sensor pattern recognition mechanism for diagnosing the LBP.


Asunto(s)
Dolor de la Región Lumbar , Dispositivos Electrónicos Vestibles , Humanos , Fenómenos Biomecánicos , Rango del Movimiento Articular , Vértebras Lumbares , Movimiento , Dolor de la Región Lumbar/diagnóstico
14.
Braz. J. Pharm. Sci. (Online) ; 58: e18837, 2022. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1374558

RESUMEN

Abstract Recently, the acetate wheat starch (AWS) has been prepared by acetylation with an acetyl content of 2.42%, containing of rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS) with 25.0%; 22.9% and 34.5%, respectively. In this study, this kind of starch was continuously evaluated with the postprandial blood glucose response and determined short-chain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. The result showed that the mice fed with AWS exhibited a very limited increase in blood glucose level and remained stable for 2 hours after meals efficiently comparing with the control group fed with natural wheat starch (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed with AWS was significantly higher than mice fed with NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Thus, AWS has shown to limit the postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs providing a part of energy for the body's activities, avoiding rotten fermentation causing digestive disorders which are inherent restrictions of normal high cellulose and fiber food.


Asunto(s)
Animales , Masculino , Femenino , Ratones , Almidón/efectos adversos , Triticum/clasificación , Hiperglucemia/patología , Acetatos/agonistas , Cromatografía Líquida de Alta Presión/métodos , Tracto Gastrointestinal/anomalías , Alimentos/clasificación , Glucosa/farmacología
15.
Nat Struct Mol Biol ; 28(10): 858-868, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34625746

RESUMEN

Phosphatase and tensin homolog (PTEN) is a phosphatidylinositol-3,4,5-triphosphate (PIP3) phospholipid phosphatase that is commonly mutated or silenced in cancer. PTEN's catalytic activity, cellular membrane localization and stability are orchestrated by a cluster of C-terminal phosphorylation (phospho-C-tail) events on Ser380, Thr382, Thr383 and Ser385, but the molecular details of this multi-faceted regulation have remained uncertain. Here we use a combination of protein semisynthesis, biochemical analysis, NMR, X-ray crystallography and computational simulations on human PTEN and its sea squirt homolog, VSP, to obtain a detailed picture of how the phospho-C-tail forms a belt around the C2 and phosphatase domains of PTEN. We also visualize a previously proposed dynamic N-terminal α-helix and show that it is key for PTEN catalysis but disordered upon phospho-C-tail interaction. This structural model provides a comprehensive framework for how C-tail phosphorylation can impact PTEN's cellular functions.


Asunto(s)
Fosfohidrolasa PTEN/química , Animales , Ciona intestinalis/química , Cristalografía por Rayos X , Polarización de Fluorescencia , Humanos , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosforilación
16.
Metabolism ; 120: 154794, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33971204

RESUMEN

PURPOSE: Preeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the identification of optimal timepoints for vascular assessment and the development of effective early screening strategies. METHODS: In this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10-13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T1R), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE. RESULTS: A changepoint in cfPWV and crPWV was detected at 14-17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22-25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18-21 weeks' gestation that was not seen in women who did not develop PrE until 30-33 weeks. No differences in T1R, PPA, or SEVR were observed between the groups. CONCLUSIONS: Altered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies.


Asunto(s)
Preeclampsia/diagnóstico , Análisis de la Onda del Pulso , Rigidez Vascular/fisiología , Adulto , Teorema de Bayes , Biomarcadores/análisis , Diagnóstico Precoz , Femenino , Edad Gestacional , Humanos , Estudios Longitudinales , Preeclampsia/fisiopatología , Embarazo , Primer Trimestre del Embarazo/fisiología , Embarazo de Alto Riesgo , Estudios Prospectivos , Quebec
17.
Environ Monit Assess ; 193(6): 319, 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33942168

RESUMEN

A rational water quality assessment program directly affects a success of a national socio-economic development strategy. This study was aimed to evaluate and classify surface water quality in Dong Thap province, Vietnam, using set pair analysis (SPA) and national water quality index (WQI_VN) methods. The water quality data was collected at 58 locations in 2019 by the Department of Natural Resources and Environment of Dong Thap province. Sixteen variables including temperature (°C), pH, turbidity (NTU), dissolved oxygen (DO, mg/L), biological oxygen demand (BOD, mg/L), chemical oxygen demand (COD, mg/L), total suspended solids (TSS, mg/L), ammonia (N-NH4+, mg/L), nitrite (N-NO2-), nitrate (N-NO3-, mg/L), total nitrogen (TN, mg/L), orthophosphate (P-PO43-, mg/L), chloride (Cl-, mg/L), sulfate (SO42-, mg/L), coliform (MPN/100 mL), and Escherichia coli (MPN/100 mL) were monitored four times a year (58 water samples × 16 parameters × 4 monitoring times). The findings presented that TSS, BOD, COD, N-NH4+, N-NO2-, P-PO43-, coliform, and E. coli were the main constraints on water quality. The results of the entropy weight calculation indicated that deteriorated water quality was in the order of microbiological > nutrients > organic matters. Surface water quality was evaluated at medium (level III) and poor (level IV) by SPA and WQI_VN, respectively; however, the combination of SPA and entropy weight was considered more efficient in this classification and a positive spatial autocorrelation was also found through Moran's I. The spatial distribution of water quality based on SPA classification revealed that better water quality was found in the inner parts of the study area. Due to its ease and effectiveness, set pair analysis should be considered for inclusion in the water quality assessment program of Vietnam.


Asunto(s)
Ríos , Calidad del Agua , Pueblo Asiatico , Monitoreo del Ambiente , Escherichia coli , Humanos , Vietnam
18.
Artículo en Inglés | MEDLINE | ID: mdl-33805495

RESUMEN

The food retail environment has been directly linked to disparities in dietary behaviors and may in part explain racial and ethnic disparities in pregnancy-related deaths. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC), administered by the United States Department of Agriculture, is associated with improved healthy food and beverage access due to its requirement for minimum stock of healthy foods and beverages in WIC-eligible stores. The selection and authorization criteria used to authorize WIC vendors varies widely from state to state with little known about the specific variations. This paper reviews and summarizes the differences across 16 of these criteria enacted by 89 WIC administrative agencies: the 50 states, the District of Columbia, five US Territories, and 33 Indian Tribal Organizations. Vendor selection and authorization criteria varied across WIC agencies without any consistent pattern. The wide variations in criteria and policies raise questions about the rational for inconsistency. Some of these variations, in combination, may result in reduced access to WIC-approved foods and beverages by WIC participants. For example, minimum square footage and/or number of cash register criteria may limit vendors to larger retail operations that are not typically located in high-risk, under-resourced communities where WIC vendors are most needed. Results highlight an opportunity to convene WIC stakeholders to review variations, their rationale, and implications thereof especially as this process could result in improved policies to ensure and improve healthy food and beverage access by WIC participants. More work remains to better understand the value of state WIC vendor authorization authority, particularly in states that have provided stronger monitoring requirements. This work might also examine if and how streamlining WIC vendor criteria (or at least certain components of them) across regional areas or across the country could provide an opportunity to advance interstate commerce and promote an equitable supply of food across the food system, while ensuring the protection for local, community-oriented WIC vendors.


Asunto(s)
Asistencia Alimentaria , Niño , Comercio , District of Columbia , Femenino , Abastecimiento de Alimentos , Humanos , Lactante , Embarazo , Estados Unidos , United States Department of Agriculture
19.
Cancer Res ; 81(12): 3319-3332, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33863778

RESUMEN

Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Here we show that increased ADA2 expression is associated with increased patient survival and enrichment of adaptive immune response pathways in several solid tumor types. Several ADA2 variants were created to improve catalytic efficiency, and PEGylation was used to prolong systemic exposure. In mice, PEGylated ADA2 (PEGADA2) inhibited tumor growth by targeting adenosine in an enzyme activity-dependent manner and thereby modulating immune responses. These findings introduce endogenous ADA2 expression as a prognostic factor and PEGADA2 as a novel immunotherapy for cancer. SIGNIFICANCE: This study identifies ADA2 as a prognostic factor associated with prolonged cancer patient survival and introduces the potential of enzymatic removal of adenosine with engineered ADA2 for cancer immunotherapy.


Asunto(s)
Adenosina Desaminasa/metabolismo , Adenosina/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias/prevención & control , Adenosina Desaminasa/genética , Animales , Apoptosis , Proliferación Celular , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Neoplasias/enzimología , Neoplasias/patología , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Spine J ; 21(7): 1135-1142, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33601012

RESUMEN

BACKGROUND: With spinal surgery rates increasing in North America, models that are able to accurately predict which patients are at greater risk of developing complications are highly warranted. However, the previously published methods which have used large, multi-centre databases to develop their prediction models have relied on the receiver operator characteristics curve with the associated area under the curve (AUC) to assess their model's performance. Recently, it has been found that a precision-recall curve with the associated F1-score could provide a more realistic analysis for these models. PURPOSE: To develop a logistic regression (LR) model for the prediction of complications following posterior lumbar spine surgery and to then assess for any difference in performance of the model when using the AUC versus the F1-score. STUDY DESIGN: Retrospective review of a prospective cohort. PATIENT SAMPLE: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry was used. All patients that underwent posterior lumbar spine surgery between 2005 to 2016 with appropriate data were included. OUTCOME MEASURES: Both the AUC and F1-score were utilized to assess the prognostic performance of the prediction model. METHODS: In order to develop the LR model used to predict a complication during or following spine surgery, 19 variables were selected by three orthopedic spine surgeons from the NSQIP registry. Two datasets were developed for this analysis: (1) an imbalanced dataset, which was taken directly from the NSQIP registry, and (2) a down-sampled set. The purpose of the down-sampled set was to balance the data in order to evaluate whether balancing the data had an effect on model performance. The AUC and F1-score were applied to both of these datasets. RESULTS: Within the NSQIP database, 52,787 spine surgery cases were identified of which only 10% of these cases had complications during surgery. Applying the LR model showed a large difference between the AUC (0.69) and the F1 score (0.075) on the imbalanced dataset. However, no major differences existed between the AUC and F1-score when the data was balanced and the LR model was reapplied (0.69 and 0.62, AUC and F1-score, respectively). CONCLUSIONS: The F1-score detected a drastically lower performance for the prediction of complications when using the imbalanced data, but detected a performance similar to the AUC level when balancing techniques were utilized for the dataset. This difference is due to a low precision score when many false positive classifications are present, which is not identified when using the AUC value. This lowers the utility of the AUC score, as many of the datasets used in medicine are imbalanced. Therefore, we recommend using the F1-score on large, prospective databases when the data is imbalanced with a large amount of true negative classifications.


Asunto(s)
Complicaciones Posoperatorias , Columna Vertebral , Humanos , América del Norte , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos
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