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1.
J Electromyogr Kinesiol ; 76: 102882, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599050

RESUMEN

This research aimed to determine whether triceps surae delayed onset muscle soreness (DOMS) affects stability while performing different postural control tasks requiring upright and landing stabilization. Twenty-four participants who self-reported as healthy were recruited. Pre and 48 h after a protocol to induce DOMS in the triceps surae, participants were evaluated for DOMS perception, pressure pain threshold, and postural control (assessed by the center of pressure, CoP) during different standing and landing stabilization tasks. We found higher DOMS perception and lower pressure pain threshold 48 h after the exercise. Mediolateral CoP displacement was more sensitive to DOMS across different postural tasks, but no effects were found for bilateral standing. The landing time to stabilization elicited high individual variability in the presence of DOMS. Effects of DOMS in the performance of less challenging tasks, such as bipedal standing, were not found. We conclude that DOMS in the triceps surae impairs mediolateral postural control during challenging tasks such as unilateral standing and body forward lean. It highlights the need for caution and individualized approaches when incorporating movements requiring frontal plane control in training and rehabilitation sessions under the presence of DOMS.


Asunto(s)
Músculo Esquelético , Mialgia , Equilibrio Postural , Postura , Humanos , Masculino , Mialgia/fisiopatología , Mialgia/etiología , Músculo Esquelético/fisiopatología , Músculo Esquelético/fisiología , Equilibrio Postural/fisiología , Femenino , Postura/fisiología , Adulto , Ejercicio Físico/fisiología , Adulto Joven , Umbral del Dolor/fisiología
2.
Arthritis Care Res (Hoboken) ; 76(2): 274-287, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37643903

RESUMEN

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.


Asunto(s)
COVID-19 , Enfermedades Reumáticas , Reumatología , Humanos , Masculino , Pandemias , Vacunas contra la COVID-19/uso terapéutico , Prueba de COVID-19 , COVID-19/epidemiología , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Factores de Riesgo , Sistema de Registros
3.
J Nucl Cardiol ; 30(6): 2514-2524, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37758962

RESUMEN

AIM: Contrast-enhanced cardiac magnetic resonance (Ce-CMR) and Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are frequently utilized in clinical practice to assess myocardial viability. However, studies evaluating direct comparison between Ce-CMR and FDG-PET have a smaller sample size, and no clear distinction between the two imaging modalities has been defined. To address this gap, we conducted a meta-analysis of studies comparing Ce-CMR and FDG-PET for the assessment of myocardial viability. METHODS: We searched PubMed, EMBASE, Scopus, and Web of Science databases from their inception to 4/20/2022 with search terms "viability" AND "heart diseases" AND "cardiac magnetic resonance imaging" AND "positron-emission tomography." We extracted patient characteristics, segment level viability assessment according to Ce-CMR and FDG-PET, and change in regional wall motion abnormalities (RWMA) at follow-up. RESULTS: We included four studies in the meta-analysis which provided viability assessment with Ce-CMR and FDG-PET in all patients and change in RWMA at follow-up. There were 82 patients among the four included studies, and 585 segments were compared for viability assessment. There were 59 (72%) males, and mean age was 65 years. The sensitivity (95% confidence interval-CI) and specificity (CI) of Ce-CMR for predicting myocardial recovery were 0.88 (0.66-0.96) and 0.64 (0.49-0.77), respectively. The sensitivity (CI) and specificity (CI) of FDG-PET for predicting myocardial recovery were 0.91 (0.63-0.99) and 0.67 (0.49-0.81), respectively. CONCLUSION: FDG-PET and Ce-CMR have comparable diagnostic parameters in myocardial viability assessment and are consistent with prior research.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Rayos X , Masculino , Humanos , Anciano , Femenino , Tomografía de Emisión de Positrones/métodos , Imagen por Resonancia Magnética/métodos , Corazón/diagnóstico por imagen , Radiofármacos , Sensibilidad y Especificidad
4.
J Sch Psychol ; 99: 101220, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37507188

RESUMEN

Writing proficiency facilitates higher achievement in educational and professional endeavors, yet most students fail to meet national writing benchmarks by the end of high school. Attentional control and overall reading skill are documented to result in better writing quality; however, most research on these relationships has focused on early elementary students (K-3rd grade. This project evaluated the relationship between attentional control, hyperactivity-impulsivity, word reading, and reading comprehension to overall writing performance on a high-stakes writing test. Participants included 266 fourth-grade struggling readers who completed the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN; Swanson et al., 2001, 2012) for attentional control and hyperactivity-impulsivity, the Woodcock-Johnson III (WJ-III; Woodcock et al., 2001) Letter-Word Identification test for word reading, the WJ-III Passage Comprehension test for reading comprehension, and the State of Texas Assessments of Academic Readiness (STAAR) writing test for overall writing. Hyperactivity-impulsivity was not related to word reading (ß = 0.02, p > .05), reading comprehension (ß = 0.06, p > .05), or writing (ß = 0.14, p > .05), whereas attentional control (ß = 0.51, p < .01) and reading comprehension (ß = 0.55, p < .001) contributed to overall writing. Reading comprehension (ß = 0.55, p < .01) had a greater impact on writing than word reading (ß = 0.13, p > .05), which suggests that as academic rigor increases in the upper elementary school grades (4th grade and higher), basic skills are less predictive of success on complex tasks such as writing. Implications for increasing writing proficiency through research and practice are discussed.


Asunto(s)
Comprensión , Lectura , Humanos , Niño , Atención , Escritura , Escolaridad
5.
J Pers Med ; 13(5)2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37240910

RESUMEN

Syncope is a form of transient loss of consciousness (TLOC) resulting from cerebral hypoperfusion and is characterized by rapid onset, short duration and spontaneous complete recovery [...].

6.
Pharmaceutics ; 15(5)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37242756

RESUMEN

At present, colorectal cancer (CRC) is the second deadliest type of cancer, partly because a high percentage of cases are diagnosed at advanced stages when tumors have already metastasized. Thus, there is an urgent need to develop novel diagnostic systems that allow early detection as well as new therapeutic systems that are more specific than those currently available. In this context, nanotechnology plays a very important role in the development of targeted platforms. In recent decades, many types of nanomaterials with advantageous properties have been used for nano-oncology applications and have been loaded with different types of targeted agents, capable of recognizing tumor cells or biomarkers. Indeed, among the different types of targeted agents, the most widely used are monoclonal antibodies, as the administration of many of them is already approved by the main drug regulatory agencies for the treatment of several types of cancer, including CRC. In this way, this review comprehensively discusses the main drawbacks of the conventional screening technologies and treatment for CRC, and it presents recent advances in the application of antibody-loaded nanoplatforms for CRC detection, therapy or theranostics applications.

7.
Sch Psychol ; 38(3): 173-181, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37184959

RESUMEN

Recent advances in automated writing evaluation have enabled educators to use automated writing quality scores to improve assessment feasibility. However, there has been limited investigation of bias for automated writing quality scores with students from diverse racial or ethnic backgrounds. The use of biased scores could contribute to implementing unfair practices with negative consequences on student learning. The goal of this study was to investigate score bias of writeAlizer, a free and open-source automated writing evaluation program. For 421 students in Grades 4 and 7 who completed a state writing exam that included composition and multiple choice revising and editing questions, writeAlizer was used to generate automated writing quality scores for the composition section. Then, we used multiple regression models to investigate whether writeAlizer scores demonstrated differential predictions of the composition and overall scores on the state-mandated writing exam for students from different racial or ethnic groups. No evidence of bias for automated scores was observed. However, after controlling for automated scores in Grade 4, we found statistically significant group differences in regression models predicting overall state test scores 3 years later but not the essay composition scores. We hypothesize that the multiple choice revising and editing sections, rather than the scoring approach used for the essay portion, introduced construct-irrelevant variance and might lead to differential performance among groups. Implications for assessment development and score use are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Evaluación Educacional , Estudiantes , Humanos , Escritura , Etnicidad
9.
JACC Case Rep ; 9: 101533, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36909267

RESUMEN

Recognizing true from pseudo left ventricular aneurysm after myocardial infarction is paramount to guide clinical management and determine need for surgical urgency. We discuss a case of a postinfarction pseudoaneurysm that poses unique anatomic challenges and may hold a secret "DaVinci code" beyond current diagnostic criteria. (Level of Difficulty: Advanced.).

10.
Eur Radiol ; 33(8): 5368-5377, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36562783

RESUMEN

OBJECTIVES: To investigate the normal-appearing white matter (NAWM) susceptibility in a cohort of newly diagnosed multiple sclerosis (MS) patients and to evaluate possible correlations between NAWM susceptibility and disability progression. METHODS: Fifty-nine patients with a diagnosis of MS (n = 53) or clinically isolated syndrome (CIS) (n = 6) were recruited and followed up. All participants underwent neurological examination, blood sampling for serum neurofilament light chain (sNfL) level assessment, lumbar puncture for the quantification of cerebrospinal fluid (CSF) ß-amyloid1-42 (Aß) levels, and brain MRI. T2-weighted scans were used to quantify white matter (WM) lesion loads. For each scan, we derived the NAWM volume fraction and the WM lesion volume fraction. Quantitative susceptibility mapping (QSM) of the NAWM was calculated using the susceptibility tensor imaging (STI) suite. Susceptibility maps were computed with the STAR algorithm. RESULTS: Primary progressive patients (n = 9) showed a higher mean susceptibility value in the NAWM than relapsing-remitting (n = 44) and CIS (n = 6) (p = 0.01 and p = 0.02). Patients with a higher susceptibility in the NAWM showed increased sNfL concentration (ρ = 0.38, p = 0.004) and lower CSF Aß levels (ρ = -0.34, p = 0.009). Mean NAWM susceptibility turned out to be a predictor of the expanded disability status scale (EDSS) worsening at follow-up (ß = 0.41, t = 2.66, p = 0.01) and of the MS severity scale (MSSS) (ß = 0.38, t = 2.43, p = 0.019). CONCLUSIONS: QSM in the NAWM seems to predict the EDSS increment over time. This finding might provide evidence on the role of QSM in identifying patients with an increased risk of early disability progression. KEY POINTS: • NAWM-QSM is higher in PPMS patients than in RRMS. • NAWM-QSM seems to be a predictor of EDSS worsening over time. • Patients with higher NAWM-QSM show increased sNfL concentration and lower CSF Aß levels.


Asunto(s)
Enfermedades Desmielinizantes , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Sustancia Blanca , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen por Resonancia Magnética/métodos , Neuroimagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Esclerosis Múltiple Recurrente-Remitente/patología
11.
Arthritis Care Res (Hoboken) ; 75(1): 61-68, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35904969

RESUMEN

OBJECTIVE: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals. METHODS: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009. Cases were matched to the National Death Index over a 10-year period. Logistic regression examined age-adjusted differences in causes of death by race, ethnicity, and sex. Age-standardized mortality ratios between individuals with SLE and the corresponding general population were calculated for the leading cause of death, and observed versus expected deaths were estimated. RESULTS: The study included 812 individuals of White (38%), Asian (36%), Black (20%), and mixed/other/unknown (5%) race; 15% identified as Hispanic. One hundred thirty-five deaths were recorded, with a mean ± SD age at death of 62.2 ± 15.6 years. Cardiovascular disease (CVD) was the leading cause of death overall (33%), and across all racial and ethnic groups, followed by rheumatic disease (18%) and hematologic/oncologic conditions (18%). CVD as the underlying cause of death was 3.63 times higher among SLE cases than in the general population. CVD deaths for those with SLE were nearly 4 and 6 times higher for Asian and Hispanic individuals with SLE, respectively, compared to the general population. CONCLUSION: Individuals with SLE experience a disproportionate burden of CVD mortality compared to the general population, which is magnified for Asian and Hispanic groups.


Asunto(s)
Enfermedades Cardiovasculares , Lupus Eritematoso Sistémico , Humanos , Persona de Mediana Edad , Anciano , Etnicidad , Causas de Muerte , Lupus Eritematoso Sistémico/epidemiología , Hispánicos o Latinos
12.
Plants (Basel) ; 13(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38202338

RESUMEN

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first committed step of the oxidative pentose phosphate pathway (OPPP). Our recent phosphoproteomics study revealed that the cytosolic G6PD6 isozyme became hyperphosphorylated at Ser12, Thr13 and Ser18, 48 h following phosphate (Pi) resupply to Pi-starved (-Pi) Arabidopsis thaliana cell cultures. The aim of the present study was to assess whether G6PD6 phosphorylation also occurs in shoots or roots following Pi resupply to -Pi Arabidopsis seedlings, and to investigate its relationship with G6PD activity. Interrogation of phosphoproteomic databases indicated that N-terminal, multi-site phosphorylation of G6PD6 and its orthologs is quite prevalent. However, the functions of these phosphorylation events remain unknown. Immunoblotting with an anti-(pSer18 phosphosite-specific G6PD6) antibody confirmed that G6PD6 from Pi-resupplied, but not -Pi, Arabidopsis cell cultures or seedlings (i.e., roots) was phosphorylated at Ser18; this correlated with a significant increase in extractable G6PD activity, and biomass accumulation. Peptide kinase assays of Pi-resupplied cell culture extracts indicated that G6PD6 phosphorylation at Ser18 is catalyzed by a Ca2+-dependent protein kinase (CDPK), which correlates with the 'CDPK-like' targeting motif that flanks Ser18. Our results support the hypothesis that N-terminal phosphorylation activates G6PD6 to enhance OPPP flux and thus the production of reducing power (i.e., NADPH) and C-skeletons needed to establish the rapid resumption of growth that ensures Pi-resupply to -Pi Arabidopsis.

13.
JACC Adv ; 2(3): 100323, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-38939607

RESUMEN

Syncope, a form of transient loss of consciousness, remains a complex medical condition for which adverse cardiovascular outcomes, including death, are of major concern but rarely occur. Current risk stratification algorithms have not completely delineated which patients benefit from hospitalization and specific interventions. Patients are often admitted unnecessarily and at high cost. Artificial intelligence (AI) and machine learning may help define the transient loss of consciousness event, diagnose the cause, assess short- and long-term risks, predict recurrence, and determine need for hospitalization and therapeutic intervention; however, several challenges remain, including medicolegal and ethical concerns. This collaborative statement, from a multidisciplinary group of clinicians, investigators, and scientists, focuses on the potential role of AI in syncope management with a goal to inspire creation of AI-derived clinical decision support tools that may improve patient outcomes, streamline diagnostics, and reduce health-care costs.

14.
Free Radic Biol Med ; 193(Pt 2): 685-693, 2022 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-36395955

RESUMEN

Oxidative stress generating DNA damage has been shown to be a key characteristic in Alzheimer's disease (AD). However, how it affects the pathogenesis of AD is not yet fully understood. Neil3 is a DNA glycosylase initiating repair of oxidative DNA base lesions and with a distinct expression pattern in proliferating cells. In brain, its function has been linked to hippocampal-dependent memory and to induction of neurogenesis after stroke and in prion disease. Here, we generated a novel AD mouse model deficient for Neil3 to study the impact of impaired oxidative base lesion repair on the pathogenesis of AD. Our results demonstrate an age-dependent decrease in amyloid-ß (Aß) plaque deposition in female Neil3-deficient AD mice, whereas no significant difference was observed in male mice. Furthermore, male but not female Neil3-deficient AD mice show reduced neural stem cell proliferation in the adult hippocampus and impaired working memory compared to controls. These effects seem to be independent of DNA repair as both sexes show increased level of oxidative base lesions in the hippocampus upon loss of Neil3. Thus, our findings suggest an age- and sex-dependent role of Neil3 in the progression of AD by altering cerebral Aß accumulation and promoting adult hippocampal neurogenesis to maintain cognitive function.


Asunto(s)
Enfermedad de Alzheimer , ADN Glicosilasas , Masculino , Femenino , Ratones , Animales , Enfermedad de Alzheimer/genética , ADN Glicosilasas/genética , Neurogénesis/genética , Modelos Animales de Enfermedad , Placa Amiloide/genética , Péptidos beta-Amiloides/genética , Trastornos de la Memoria
15.
PLoS One ; 17(10): e0274943, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36256646

RESUMEN

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15µg H7N9, 1B) IB160 + 7.5µg H7N9, 1C) IB160 + 3.75µg H7N9, 2A) SE + 15µg H7N9, 2B) SE + 7.5µg H7N9, 2C) SE + 3.75µg H7N9, 3) unadjuvanted vaccine 15µg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Escualeno , Pandemias/prevención & control , Polisorbatos , Emulsiones , Anticuerpos Antivirales , Pruebas de Inhibición de Hemaglutinación , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Agua
16.
Lancet Rheumatol ; 4(9): e603-e613, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35909441

RESUMEN

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.

17.
Carbohydr Polym ; 294: 119732, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-35868800

RESUMEN

Hydrogels loaded with chemotherapeutics are promising tools for local tumor treatment. In this work, redox-responsive implantable hydrogels based on gellan gum were prepared as paclitaxel carriers for HER2-positive breast cancer therapy. To achieve different degrees of chemical crosslinking, hydrogels were synthesized in both acetate buffer and phosphate buffer and crosslinked with different concentrations of l-cysteine. It was shown that both, the type of buffer and the l-cysteine concentration used, conditioned the dynamic modulus, equilibrium swelling rate, porosity, and thermal stability of the hydrogels. Then, the biocompatibility of the hydrogels with the most suitable porosity for drug delivery applications was assessed. Once confirmed, these hydrogels were loaded with paclitaxel:ß-cyclodextrin inclusion complexes, and they showed a glutathione-responsive controlled release of the taxane. Moreover, when tested in vitro, paclitaxel-loaded hydrogels exhibited great antitumor activity. Thus, they could act as excellent local tailored carriers of paclitaxel for future, post-surgical treatment of HER2-overexpressing breast tumors.


Asunto(s)
Neoplasias de la Mama , Hidrogeles , Neoplasias de la Mama/tratamiento farmacológico , Cisteína , Femenino , Humanos , Hidrogeles/química , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Polisacáridos Bacterianos/química
18.
ACR Open Rheumatol ; 4(10): 872-882, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35869686

RESUMEN

OBJECTIVE: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. METHODS: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. RESULTS: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. CONCLUSION: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.

19.
J Sch Psychol ; 92: 80-95, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35618384

RESUMEN

Although researchers have investigated technical adequacy and usability of written-expression curriculum-based measures (WE-CBM), the economic implications of different scoring approaches have largely been ignored. The absence of such knowledge can undermine the effective allocation of resources and lead to the adoption of suboptimal measures for the identification of students at risk for poor writing outcomes. Therefore, we used the Ingredients Method to compare implementation costs and cost-effectiveness of hand-calculated and automated scoring approaches. Data analyses were conducted on secondary data from a study that evaluated predictive validity and diagnostic accuracy of quantitative approaches for scoring WE-CBM samples. Findings showed that automated approaches offered more economic solutions than hand-calculated methods; for automated scores, the effects were stronger when the free writeAlizer R package was employed, whereas for hand-calculated scores, simpler WE-CBM metrics were less costly than more complex metrics. Sensitivity analyses confirmed the relative advantage of automated scores when the number of classrooms, students, and assessment occasions per school year increased; again, writeAlizer was less sensitive to the changes in the ingredients than the other approaches. Finally, the visualization of the cost-effectiveness ratio illustrated that writeAlizer offered the optimal balance between implementation costs and diagnostic accuracy, followed by complex hand-calculated metrics and a proprietary automated program. Implications for the use of hand-calculated and automated scores for the universal screening of written expression with elementary students are discussed.


Asunto(s)
Evaluación Educacional , Escritura , Niño , Análisis Costo-Beneficio , Curriculum , Evaluación Educacional/métodos , Humanos , Tamizaje Masivo
20.
Genes (Basel) ; 13(2)2022 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-35205344

RESUMEN

Metopaulias depressus is a non-marine crab endemic to Jamaica that dwells in rainforest bromeliads and exhibits elaborate active parental care behavior. Current genomic resources on M. depressus are rare, limiting the understanding of its adaptation to terrestrial life in species that evolved from marine ancestors. This study reports the complete mitochondrial genome of M. depressus assembled using Sanger sequencing. The AT-rich mitochondrial genome of M. depressus is 15,765 bp in length and comprises 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. A single 691 bp-long intergenic space is assumed to be the control region (CR) or D-loop. A set of selective pressure analyses indicate that the entirety of the PCGs experience purifying selection. Cox1, cox2, nad5, cox3, and atp6 experience strong purifying selection, and atp8 experiences weak purifying selection compared to the rest of the PCGs. The secondary structures of most tRNA genes exhibit a standard 'cloverleaf' structure, with the exception of trnS1, which lacks the dihydroxyuridine (DHU) arm but not the loop, the trnH gene, which lacks the thymine pseudouracil cytosine (T) loop but not the arm, and trnM, which exhibits an overly developed T loop. A maximum likelihood phylogenetic analysis based on all PCGs indicated that M. depressus is more closely related to the genera Clistocoeloma, Nanosesarma, and Parasesarma than to Chiromantes, Geosesarma, and Orisarma. This study contributes to deciphering the phylogenetic relationships within the family Sesarmidae and represents a new genomic resource for this iconic crab species.


Asunto(s)
Braquiuros , Genoma Mitocondrial , Animales , Braquiuros/genética , Genoma Mitocondrial/genética , Genómica , Filogenia , ARN de Transferencia/genética
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