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1.
Artículo en Inglés | MEDLINE | ID: mdl-39135467

RESUMEN

BACKGROUND: The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria development, aiming to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, organized into laboratory and clinical domains. Here, we summarize the last stage of Phase III efforts employing a consensus-based multi-criteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score. METHODS: We evaluated 192 unique, international real-world cases referred for "suspected APS" with a wide range of APS manifestations. Using proposed candidate criteria, subcommittee members rank-ordered 20 representative cases from highly unlikely to highly likely APS. During an in-person meeting, the subcommittee refined definitions and participated in an MCDA exercise to identify relative weights of candidate criteria. Using consensus decisions and pairwise criteria comparisons, 1000Minds™ software assigned criteria weights, and we rank ordered 192 cases by their additive scores. A consensus-based threshold score for APS classification was set. RESULTS: Pre-meeting evaluation of 20 representative cases demonstrated variability in APS assessment. MCDA resolved 81 pairwise decisions; relative weights identified domain item hierarchy. After assessing 192 cases by weights and additive scores, the Steering Committee reached consensus that APS classification should require separate clinical and laboratory scores, rather than a single aggregate score, to ensure high specificity. CONCLUSION: Using MCDA, candidate criteria preliminary weights were determined. Unlike other disease classification systems using a single aggregate threshold score, separate clinical and laboratory domain thresholds were incorporated into the new APS classification criteria.

2.
J Fish Biol ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150971

RESUMEN

Gaidropsarus mauritanicus sp. nov. is described from one specimen collected using a grab sample from the Tanoûdêrt Canyon (ca. 20° N) off Mauritania at a depth of 595 m. The new species was further observed during eight remotely operated vehicle (ROV) dives along the Mauritanian slope southwards down to the Tiguent Coral Mound Complex (~17° N) in a bathymetric range between 613 and 416 m. It can be distinguished from congeners by a combination of characteristics, including large eyes (38.1% head length [HL]), large head (25.8% standard length [SL]), elongated pelvic fins (35.7% SL), low number of vertebrae (44), and coloration (pinkish with a dorsal darker brownish hue and bright blotches along the dorsal-fin base). A species-delimitation analysis performed with available cytochrome c oxidase subunit 1 (COI) sequences affiliated to the genus Gaidropsarus additionally supported the validity of the new species. Video analyses showed a deep-water coral-associated and protection-seeking behavior, which may explain why the species has remained undescribed until now. Additional ROV footage from separate deep-water coral sites in the North Atlantic and Mediterranean Sea further highlights the ecological behavior and hidden diversity of bathyal three-bearded rocklings. Here, we additionally discuss the biogeographical distribution of all genetically verified Gaidropsarus spp. in combination with genetic data and morphological characters. G. mauritanicus sp. nov. is closely related to a species from Tasmania (43° S), a geographical point furthest among the studied samples, which may hint to an important influence of (paleo-) oceanography on the distributions of Gaidropsarus species.

3.
Stat Methods Med Res ; : 9622802241268488, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140295

RESUMEN

Multivariate disease mapping is important for public health research, as it provides insights into spatial patterns of health outcomes. Geostatistical methods that are widely used for mapping spatially correlated health data encounter challenges when dealing with spatial count data. These include heterogeneity, zero-inflated distributions and unreliable estimation, and lead to difficulties when estimating spatial dependence and poor predictions. Variability in population sizes further complicates risk estimation from the counts. This study introduces multivariate Poisson cokriging for predicting and filtering out disease risk. Pairwise correlations between the target variable and multiple ancillary variables are included. By means of a simulation experiment and an application to human immunodeficiency virus incidence and sexually transmitted diseases data in Pennsylvania, we demonstrate accurate disease risk estimation that captures fine-scale variation. This method is compared with ordinary Poisson kriging in prediction and smoothing. Results of the simulation study show a reduction in the mean square prediction error when utilizing auxiliary correlated variables, with mean square prediction error values decreasing by up to 50%. This gain is further evident in the real data analysis, where Poisson cokriging yields a 74% drop in mean square prediction error relative to Poisson kriging, underscoring the value of incorporating secondary information. The findings of this work stress on the potential of Poisson cokriging in disease mapping and surveillance, offering richer risk predictions, better representation of spatial interdependencies, and identification of high-risk and low-risk areas.

4.
Glob Chang Biol ; 30(7): e17414, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39044553

RESUMEN

As climatic variation re-shapes global biodiversity, understanding eco-evolutionary feedbacks during species range shifts is of increasing importance. Theory on range expansions distinguishes between two different forms: "pulled" and "pushed" waves. Pulled waves occur when the source of the expansion comes from low-density peripheral populations, while pushed waves occur when recruitment to the expanding edge is supplied by high-density populations closer to the species' core. How extreme events shape pushed/pulled wave expansion events, as well as trailing-edge declines/contractions, remains largely unexplored. We examined eco-evolutionary responses of a marine invertebrate (the owl limpet, Lottia gigantea) that increased in abundance during the 2014-2016 marine heatwaves near the poleward edge of its geographic range in the northeastern Pacific. We used whole-genome sequencing from 19 populations across >11 degrees of latitude to characterize genomic variation, gene flow, and demographic histories across the species' range. We estimated present-day dispersal potential and past climatic stability to identify how contemporary and historical seascape features shape genomic characteristics. Consistent with expectations of a pushed wave, we found little genomic differentiation between core and leading-edge populations, and higher genomic diversity at range edges. A large and well-mixed population in the northern edge of the species' range is likely a result of ocean current anomalies increasing larval settlement and high-dispersal potential across biogeographic boundaries. Trailing-edge populations have higher differentiation from core populations, possibly driven by local selection and limited gene flow, as well as high genomic diversity likely as a result of climatic stability during the Last Glacial Maximum. Our findings suggest that extreme events can drive poleward range expansions that carry the adaptive potential of core populations, while also cautioning that trailing-edge extirpations may threaten unique evolutionary variation. This work highlights the importance of understanding how both trailing and leading edges respond to global change and extreme events.


Asunto(s)
Evolución Biológica , Cambio Climático , Animales , Flujo Génico , Dinámica Poblacional , Distribución Animal , Variación Genética
5.
Biol Open ; 13(7)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39052046

RESUMEN

During programmed cell death (PCD), it is commonly accepted that macrophages are recruited by apoptotic cells to complete cell degradation. Interdigital cell death, a classical model of PCD, contributes to digit individualization in limbs of mammals and other vertebrates. Here, we show that macrophages are present in interdigits before significant cell death occurs and remain after apoptosis inhibition. The typical interdigital phagocytic activity was not observed after a partial depletion of macrophages and was markedly reduced by engulfment/phagosome maturation inhibition, as detected by its association with high lysosomal activity. ß-galactosidase activity in this region was also coupled with phagocytosis, against its relationship with cellular senescence. Interdigital phagocytosis correlated with high levels of reactive oxygen species (ROS), common in embryo regions carrying abundant cell death, suggesting that macrophages are the major source of ROS. ROS generation was dependent on NADPH oxidases and blood vessel integrity, but not directly associated with lysosomal activity. Therefore, macrophages prepattern regions where abundant cell death is going to occur, and high lysosomal activity and the generation of ROS by an oxidative burst-like phenomenon are activities of phagocytosis.


Asunto(s)
Apoptosis , Lisosomas , Macrófagos , Fagocitosis , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/metabolismo , Animales , Lisosomas/metabolismo , Ratones , NADPH Oxidasas/metabolismo
6.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000111

RESUMEN

A new family of antifibrinolytic drugs has been recently discovered, combining a triazole moiety, an oxadiazolone, and a terminal amine. Two of the molecules of this family have shown activity that is greater than or similar to that of tranexamic acid (TXA), the current antifibrinolytic gold standard, which has been associated with several side effects and whose use is limited in patients with renal impairment. The aim of this work was to thoroughly examine the mechanism of action of the two ideal candidates of the 1,2,3-triazole family and compare them with TXA, to identify an antifibrinolytic alternative active at lower dosages. Specifically, the antifibrinolytic activity of the two compounds (1 and 5) and TXA was assessed in fibrinolytic isolated systems and in whole blood. Results revealed that despite having an activity pathway comparable to that of TXA, both compounds showed greater activity in blood. These differences could be attributed to a more stable ligand-target binding to the pocket of plasminogen for compounds 1 and 5, as suggested by molecular dynamic simulations. This work presents further evidence of the antifibrinolytic activity of the two best candidates of the 1,2,3-triazole family and paves the way for incorporating these molecules as new antifibrinolytic therapies.


Asunto(s)
Antifibrinolíticos , Ácido Tranexámico , Triazoles , Triazoles/química , Triazoles/farmacología , Antifibrinolíticos/farmacología , Antifibrinolíticos/química , Humanos , Ácido Tranexámico/farmacología , Ácido Tranexámico/química , Simulación de Dinámica Molecular , Plasminógeno/metabolismo , Plasminógeno/química , Fibrinólisis/efectos de los fármacos
7.
Angew Chem Int Ed Engl ; : e202409226, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995733

RESUMEN

The synthesis of housanes derivatives from cyclopropenes is described. Under rhodium(II) catalysis, cyclopropenylvinyl carbinols can regioselectively generate a carbene intermediate which undergo an intramolecular cyclopropanation to form a housane, a skeleton with similar ring strain as the cyclopropene precursor. The procedure shows a remarkable broad scope and efficiency. Moreover, the method served to prepare man-made housane-containing terpene derivatives, which are not accessible by Nature.

8.
J Cell Biol ; 223(10)2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-38949648

RESUMEN

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.


Asunto(s)
Anafase , Proteínas de Drosophila , Drosophila melanogaster , Dineínas , Microtúbulos , Animales , Dineínas/metabolismo , Dineínas/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Microtúbulos/metabolismo , Microtúbulos/genética , Simulación de Dinámica Molecular , Mutación/genética , Huso Acromático/metabolismo , Huso Acromático/genética , Humanos , Mutación Missense
9.
medRxiv ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38978675

RESUMEN

Purpose: This study presents the biodistribution, clearance and dosimetry estimates of [64Cu]Fibrin Binding Probe #8 ([64Cu]FBP8) in healthy subjects. Procedures: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [64Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 hours, 4h and 24h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software. Results: Subjects were injected with ~400 MBq of [64Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [64Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [18F]fluorodeoxyglucose ([18F]FDG, 0.020mSv/MBq). Conclusions: This study demonstrates the following properties of the [64Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 minutes in a single session. These properties provide the basis for [64Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.

10.
Alzheimers Dement ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38961808

RESUMEN

INTRODUCTION: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application. METHODS: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL. RESULTS: RR selection and RR type impact CL the most, particularly in amyloid-negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24). DISCUSSION: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings. HIGHLIGHTS: We developed a framework for evaluating Centiloid (CL) variability to different factors. Reference region selection and delineation had the highest impact on CL values. Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers. The standard CL pipeline is robust against atrophy and image resolution variation. Estimated within- and between-pipeline variability (95% confidence interval) in absolute CL units.

11.
Ann Epidemiol ; 96: 48-52, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880361

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer with few treatment options available to patients. Most HCC cases in Arizona, a state with a high proportion of Hispanic adults, have not been included in recent reports of HCC incidence. This study describes trends in HCC incidence and stage at diagnosis among Arizona residents between 2009-2017 and reports on racial and ethnic disparities for these outcomes. METHODS: The Arizona Cancer Registry was used to identify Arizonans aged 19 or older diagnosed with liver cell carcinoma diagnosed between 2009-2017. A total of 5043 cases were examined. Adjusted annual and 3-year HCC incidence rates (per 100,000) were examined for non-Hispanic White (NHW) and Hispanic adults. RESULTS: The total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017. CONCLUSION: Whe total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017.


Asunto(s)
Carcinoma Hepatocelular , Hispánicos o Latinos , Neoplasias Hepáticas , Población Blanca , Humanos , Arizona/epidemiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etnología , Femenino , Masculino , Carcinoma Hepatocelular/etnología , Carcinoma Hepatocelular/epidemiología , Incidencia , Hispánicos o Latinos/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Anciano , Población Blanca/estadística & datos numéricos , Disparidades en el Estado de Salud , Sistema de Registros , Adulto Joven , Anciano de 80 o más Años
12.
J Antimicrob Chemother ; 79(8): 1794-1800, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38863341

RESUMEN

OBJECTIVES: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort. METHODS: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC. RESULTS: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC. CONCLUSIONS: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated.


Asunto(s)
Bacteriemia , Humanos , Estudios Prospectivos , Masculino , Femenino , Bacteriemia/mortalidad , Bacteriemia/microbiología , Anciano , Persona de Mediana Edad , España/epidemiología , Anciano de 80 o más Años , Adulto , Factores de Riesgo , Pronóstico , Modelos Logísticos
13.
Alzheimers Res Ther ; 16(1): 130, 2024 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886831

RESUMEN

BACKGROUND: There is good evidence that elevated amyloid-ß (Aß) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aß burden and decline in daily living activities in this population. Moreover, Aß-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established. METHODS: Cross-sectional and longitudinal analyses over a mean three-year timeframe were performed on the European amyloid-PET imaging AMYPAD-PNHS dataset that phenotypes 1260 individuals, including 1032 CN individuals and 228 participants with questionable functional impairment. Amyloid-PET was assessed continuously on the Centiloid (CL) scale and using Aß groups (CL < 12 = Aß-, 12 ≤ CL ≤ 50 = Aß-intermediate/Aß± , CL > 50 = Aß+). Functional abilities were longitudinally assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). The Global-CDR was available for the 1260 participants at baseline, while baseline CDR-SOB and A-IADL-Q scores and longitudinal functional data were available for different subsamples that had similar characteristics to those of the entire sample. RESULTS: Participants included 765 Aß- (61%, Mdnage = 66.0, IQRage = 61.0-71.0; 59% women), 301 Aß± (24%; Mdnage = 69.0, IQRage = 64.0-75.0; 53% women) and 194 Aß+ individuals (15%, Mdnage = 73.0, IQRage = 68.0-78.0; 53% women). Cross-sectionally, CL values were associated with CDR outcomes. Longitudinally, baseline CL values predicted prospective changes in the CDR-SOB (bCL*Time = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (bCL*Time = -0.010/CL/year, 95% CI [-0.016,-0.004], p = .002) scores in initially CN participants. Increased clinical progression (Global-CDR > 0) was mainly observed in Aß+ CN individuals (HRAß+ vs Aß- = 2.55, 95% CI [1.16,5.60], p = .020). Optimal thresholds for predicting decline were found at 41 CL using the CDR-SOB (bAß+ vs Aß- = 0.137/year, 95% CI [0.069,0.206], p < .001) and 28 CL using the A-IADL-Q (bAß+ vs Aß- = -0.693/year, 95% CI [-1.179,-0.208], p = .005). CONCLUSIONS: Amyloid-PET quantification supports the identification of CN individuals at risk of functional decline. TRIAL REGISTRATION: The AMYPAD PNHS is registered at www.clinicaltrialsregister.eu with the EudraCT Number: 2018-002277-22.


Asunto(s)
Actividades Cotidianas , Péptidos beta-Amiloides , Tomografía de Emisión de Positrones , Humanos , Tomografía de Emisión de Positrones/métodos , Femenino , Masculino , Estudios Transversales , Estudios Longitudinales , Anciano , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Anciano de 80 o más Años
14.
Neurology ; 103(1): e209419, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38862136

RESUMEN

BACKGROUND AND OBJECTIVES: Discordance between CSF and PET biomarkers of ß-amyloid (Aß) might reflect an imbalance between soluble and aggregated species, possibly reflecting disease heterogeneity. Previous studies generally used binary cutoffs to assess discrepancies in CSF/PET biomarkers, resulting in a loss of information on the extent of discordance. In this study, we (1) jointly modeled Aß-CSF/PET data to derive a continuous measure of the imbalance between soluble and fibrillar pools of Aß, (2) investigated factors contributing to this imbalance, and (3) examined associations with cognitive trajectories. METHODS: Across 822 cognitively unimpaired (n = 261) and cognitively impaired (n = 561) Alzheimer's Disease Neuroimaging Initiative individuals (384 [46.7%] females, mean age 73.0 ± 7.4 years), we fitted baseline CSF-Aß42 and global Aß-PET to a hyperbolic regression model, deriving a participant-specific Aß-aggregation score (standardized residuals); negative values represent more soluble relative to aggregated Aß and positive values more aggregated relative to soluble Aß. Using linear models, we investigated whether methodological factors, demographics, CSF biomarkers, and vascular burden contributed to Aß-aggregation scores. With linear mixed models, we assessed whether Aß-aggregation scores were predictive of cognitive functioning. Analyses were repeated in an early independent validation cohort of 383 Amyloid Imaging to Prevent Alzheimer's Disease Prognostic and Natural History Study individuals (224 [58.5%] females, mean age 65.2 ± 6.9 years). RESULTS: The imbalance model could be fit (pseudo-R2 = 0.94) in both cohorts, across CSF kits and PET tracers. Although no associations were observed with the main methodological factors, lower Aß-aggregation scores were associated with larger ventricular volume (ß = 0.13, p < 0.001), male sex (ß = -0.18, p = 0.019), and homozygous APOE-ε4 carriership (ß = -0.56, p < 0.001), whereas higher scores were associated with increased uncorrected CSF p-tau (ß = 0.17, p < 0.001) and t-tau (ß = 0.16, p < 0.001), better baseline executive functioning (ß = 0.12, p < 0.001), and slower global cognitive decline (ß = 0.14, p = 0.006). In the validation cohort, we replicated the associations with APOE-ε4, CSF t-tau, and, although modestly, with cognition. DISCUSSION: We propose a novel continuous model of Aß CSF/PET biomarker imbalance, accurately describing heterogeneity in soluble vs aggregated Aß pools in 2 independent cohorts across the full Aß continuum. Aß-aggregation scores were consistently associated with genetic and AD-associated CSF biomarkers, possibly reflecting disease heterogeneity beyond methodological influences.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Masculino , Péptidos beta-Amiloides/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Anciano de 80 o más Años , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Persona de Mediana Edad
15.
Artículo en Inglés | MEDLINE | ID: mdl-38833092

RESUMEN

BACKGROUND: Guided by Andersen's Behavioral Model of Health Services Use (BMHSU), this study aimed to identify determinants of post-migration healthcare use among a sample of Mexican immigrants in a US-Mexico border region in Southern Arizona, while considering pre-migration health and healthcare experiences. METHODS: A non-probabilistic convenience sample of 300 adult Mexican immigrants completed a telephone survey to assess healthcare practices. Multivariable logistic regressions were fitted to determine adjusted relationships between frequency of care and predisposing, enabling, need, and contextual factors as well as personal health practices. RESULTS: Overall, participants had a 79% probability of receiving healthcare "at least once a year" after migrating to Southern Arizona. Receiving post-migration healthcare was associated with predisposing, enabling, need, contextual factors, and personal health practices (p < 0.05). DISCUSSION: Consistent with BMHSU, our findings suggest that frequency of healthcare is not only a function of having post-migration health insurance but is also shaped by a complex array of other factors. The results of this study shed light onto potential areas to be leveraged by multifactorial sociocultural interventions to increase Mexican immigrants' frequency of healthcare services use.

16.
Support Care Cancer ; 32(6): 334, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722345

RESUMEN

PURPOSE: To describe the characteristics of and the associations between health-related quality of life, pain, craniomandibular function, and psychosocial factors related to pain and fear of movement in patients with head and neck cancer. METHODS: Seventy-eight patients diagnosed with HNC were recruited. Measurements of the maximum mouth opening range and pressure pain thresholds on the masseter muscle and the distal phalanx of the thumb were conducted, as well as a battery of self-report questionnaires were administrated, including the QoL Questionnaire (EORT QLQ-H&N35), Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), the Spanish translation of the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD), and the short version of the Craniofacial Pain and Disability Inventory (CF-PDI-11). RESULTS: The study sample (66.7% men, mean age 60.12 [11.95] years) experienced a moderate impact on their QoL levels (57.68 [18.25] EORT QLQ-H&N35) and high kinesiophobia values (20.49 [9.11] TSK-TMD). Pain was present in 41% of the patients, but only 3.8% reported severe pain. 26.4% had a restricted mouth opening range, and 34.62% showed significant catastrophism levels. There were strong positive correlations between EORT QLQ-H&N35 and CF-PDI-11 (r = 0.81), between NRS and CF-PDI-11 (r = 0.74), and between PCS and CF-PDI-11 (r = 0.66). CONCLUSION: Patients with HNC experience negative effects in their QoL, related to their impairment in craniomandibular function. Fear of movement, pain intensity, and catastrophism are associated with poorer functionality; relationships that should be considered when attempting to improve health care.


Asunto(s)
Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/psicología , Neoplasias de Cabeza y Cuello/complicaciones , Anciano , Encuestas y Cuestionarios , Dimensión del Dolor , Movimiento , Trastornos de la Articulación Temporomandibular/psicología , Trastornos de la Articulación Temporomandibular/fisiopatología , Miedo/psicología , Estudios Transversales , Dolor en Cáncer/psicología , Adulto , Umbral del Dolor/psicología
17.
Soc Sci Med ; 351: 116982, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38788427

RESUMEN

Mexicans in the United States have been reported to maintain practices of Mexican traditional medicine at comparably higher rates than most other populations, including other Latino sub-groups. In this cross-sectional study, we examined the pre- and post-migration traditional medicine practices of first-generation immigrants from Mexico living in southern Arizona. Our objective was to assess how migration affected Mexican immigrants' ethnomedical practices and to better understand the mechanisms and motivating factors for the post-migration maintenance of practice. We designed a survey instrument based off prior qualitative data on traditional medicine practices and translated it into Spanish. The survey measured the rates and frequency of six domains of lay healing practices: herbal medicine, healing foods, self-medication with over-the-counter medicine, and three types of specialty healers (curandero/a, and sobador/a, or partero/a), and asked questions about knowledge sources, reasons for maintaining practice post-migration, and to what extent participants believed the remedies were effective. The research team fielded the telephone-based survey from April 2022 to February 2023 to 300 first-generation adult Mexican immigrants residing in southern Arizona. A series of proportions tests were conducted to examine differences in reliance on lay healing pre- and post-migration as well as to assess differences between women's and men's lay practices. The data indicate a general, but moderated decline in lay medical practices post-migration, with the usage of expert healers declining at much higher rates than the three self-care domains. Women tend to use herbal medicine and healing foods at higher rates than men post-migration. This cross-sectional quantitative study confirms prior research indicating that traditional medicine practices are heavily relied upon by Mexican origin people both pre- and post-migration. These findings suggest that public health messaging and medical providers should better address and harness Mexican immigrants' lay medical practices in order to optimize health in this population.


Asunto(s)
Medicina Tradicional , Humanos , Arizona , Masculino , Femenino , Estudios Transversales , Medicina Tradicional/estadística & datos numéricos , Medicina Tradicional/métodos , Adulto , Persona de Mediana Edad , Emigrantes e Inmigrantes/estadística & datos numéricos , Emigrantes e Inmigrantes/psicología , Americanos Mexicanos/estadística & datos numéricos , Americanos Mexicanos/psicología , México/etnología , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Anciano , Pueblos de América del Norte
18.
Ann Clin Transl Neurol ; 11(6): 1541-1556, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38757392

RESUMEN

OBJECTIVE: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. METHODS: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid ß1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. RESULTS: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. INTERPRETATION: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades de los Pequeños Vasos Cerebrales , Imagen de Difusión Tensora , Sustancia Blanca , Humanos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Masculino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Anciano , Persona de Mediana Edad , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/metabolismo , Estudios Prospectivos
19.
JMIR Public Health Surveill ; 10: e51191, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801767

RESUMEN

BACKGROUND: Understanding the patterns of disease importation through international travel is paramount for effective public health interventions and global disease surveillance. While global airline network data have been used to assist in outbreak prevention and effective preparedness, accurately estimating how these imported cases disseminate locally in receiving countries remains a challenge. OBJECTIVE: This study aimed to describe and understand the regional distribution of imported cases of dengue and malaria upon arrival in Spain via air travel. METHODS: We have proposed a method to describe the regional distribution of imported cases of dengue and malaria based on the computation of the "travelers' index" from readily available socioeconomic data. We combined indicators representing the main drivers for international travel, including tourism, economy, and visits to friends and relatives, to measure the relative appeal of each region in the importing country for travelers. We validated the resulting estimates by comparing them with the reported cases of malaria and dengue in Spain from 2015 to 2019. We also assessed which motivation provided more accurate estimates for imported cases of both diseases. RESULTS: The estimates provided by the best fitted model showed high correlation with notified cases of malaria (0.94) and dengue (0.87), with economic motivation being the most relevant for imported cases of malaria and visits to friends and relatives being the most relevant for imported cases of dengue. CONCLUSIONS: Factual descriptions of the local movement of international travelers may substantially enhance the design of cost-effective prevention policies and control strategies, and essentially contribute to decision-support systems. Our approach contributes in this direction by providing a reliable estimate of the number of imported cases of nonendemic diseases, which could be generalized to other applications. Realistic risk assessments will be obtained by combining this regional predictor with the observed local distribution of vectors.


Asunto(s)
Dengue , Malaria , Viaje , Humanos , España/epidemiología , Dengue/epidemiología , Malaria/epidemiología , Malaria/prevención & control , Viaje/estadística & datos numéricos , Enfermedades Transmisibles Importadas/epidemiología , Enfermedades Transmisibles Importadas/prevención & control , Modelos Estadísticos
20.
PLoS One ; 19(5): e0300917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38743759

RESUMEN

Suicide-related media content has preventive or harmful effects depending on the specific content. Proactive media screening for suicide prevention is hampered by the scarcity of machine learning approaches to detect specific characteristics in news reports. This study applied machine learning to label large quantities of broadcast (TV and radio) media data according to media recommendations reporting suicide. We manually labeled 2519 English transcripts from 44 broadcast sources in Oregon and Washington, USA, published between April 2019 and March 2020. We conducted a content analysis of media reports regarding content characteristics. We trained a benchmark of machine learning models including a majority classifier, approaches based on word frequency (TF-IDF with a linear SVM) and a deep learning model (BERT). We applied these models to a selection of more simple (e.g., focus on a suicide death), and subsequently to putatively more complex tasks (e.g., determining the main focus of a text from 14 categories). Tf-idf with SVM and BERT were clearly better than the naive majority classifier for all characteristics. In a test dataset not used during model training, F1-scores (i.e., the harmonic mean of precision and recall) ranged from 0.90 for celebrity suicide down to 0.58 for the identification of the main focus of the media item. Model performance depended strongly on the number of training samples available, and much less on assumed difficulty of the classification task. This study demonstrates that machine learning models can achieve very satisfactory results for classifying suicide-related broadcast media content, including multi-class characteristics, as long as enough training samples are available. The developed models enable future large-scale screening and investigations of broadcast media.


Asunto(s)
Aprendizaje Automático , Medios de Comunicación de Masas , Humanos , Suicidio , Prevención del Suicidio , Oregon , Washingtón , Aprendizaje Profundo
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