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1.
Plant Cell ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102899

RESUMEN

Elevated temperatures impair pollen performance and reproductive success, resulting in lower crop yields. The tomato (Solanum lycopersicum) anthocyanin reduced (are) mutant harbors a mutation in FLAVANONE 3-HYDROXYLASE (F3H), resulting in impaired flavonol antioxidant biosynthesis. The are mutant has reduced pollen performance and seed set relative to the VF36 parental line, phenotypes that are accentuated at elevated temperatures. Transformation of are with the wild-type F3H gene, or chemical complementation with flavonols, prevented temperature-dependent reactive oxygen species (ROS) accumulation in pollen and restored the reduced viability, germination, and tube elongation of are to VF36 levels. Overexpression of F3H in VF36 prevented temperature-driven ROS increases and impaired pollen performance, revealing that flavonol biosynthesis promotes thermotolerance. Although stigmas of are had reduced flavonol and elevated ROS levels, the growth of are pollen tubes was similarly impaired in both are and VF36 pistils. RNA-seq was performed at optimal and stress temperatures in are, VF36, and the F3H overexpression line at multiple timepoints across pollen tube elongation. The number of differentially expressed genes increased over time under elevated temperatures in all genotypes, with the greatest number in are. These findings suggest potential agricultural interventions to combat the negative effects of heat-induced ROS in pollen that lead to reproductive failure.

2.
Nucleic Acids Res ; 52(5): 2372-2388, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38214234

RESUMEN

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.


Asunto(s)
Neoplasias Encefálicas , Glioma , Histonas , Niño , Humanos , Neoplasias Encefálicas/patología , Reparación del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Glioma/patología , Histonas/genética , Histonas/metabolismo , Mutación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética
3.
Proc Natl Acad Sci U S A ; 120(4): e2212813120, 2023 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-36649417

RESUMEN

The immune system must be able to respond to a myriad of different threats, each requiring a distinct type of response. Here, we demonstrate that the cytoplasmic lysine deacetylase HDAC7 in macrophages is a metabolic switch that triages danger signals to enable the most appropriate immune response. Lipopolysaccharide (LPS) and soluble signals indicating distal or far-away danger trigger HDAC7-dependent glycolysis and proinflammatory IL-1ß production. In contrast, HDAC7 initiates the pentose phosphate pathway (PPP) for NADPH and reactive oxygen species (ROS) production in response to the more proximal threat of nearby bacteria, as exemplified by studies on uropathogenic Escherichia coli (UPEC). HDAC7-mediated PPP engagement via 6-phosphogluconate dehydrogenase (6PGD) generates NADPH for antimicrobial ROS production, as well as D-ribulose-5-phosphate (RL5P) that both synergizes with ROS for UPEC killing and suppresses selective inflammatory responses. This dual functionality of the HDAC7-6PGD-RL5P axis prioritizes responses to proximal threats. Our findings thus reveal that the PPP metabolite RL5P has both antimicrobial and immunomodulatory activities and that engagement of enzymes in catabolic versus anabolic metabolic pathways triages responses to different types of danger for generation of inflammatory versus antimicrobial responses, respectively.


Asunto(s)
Antiinfecciosos , Triaje , Especies Reactivas de Oxígeno/metabolismo , NADP/metabolismo , Macrófagos/metabolismo , Antiinfecciosos/metabolismo , Vía de Pentosa Fosfato/fisiología
4.
FASEB J ; 38(3): e23460, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38315443

RESUMEN

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long-lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA-Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus-derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Extractos del Timo , Humanos , Ratas , Animales , Bovinos , Extractos del Timo/farmacología , Extractos del Timo/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Neuronas , Neuroglía , Hipocampo , Modelos Animales de Enfermedad
5.
Neuroimage ; 290: 120564, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38442778

RESUMEN

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Imagen de Difusión Tensora , Fluorodesoxiglucosa F18 , Imagen por Resonancia Magnética , Atrofia , Enfermedad de Alzheimer/metabolismo
6.
Lancet ; 402(10409): 1251-1260, 2023 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-37805216

RESUMEN

BACKGROUND: Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. METHODS: In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. We collected blood, analysed cfDNA, and returned results to participants' doctors. If a methylation signature indicative of cancer was detected, predicted cancer signal origin(s) informed diagnostic assessment. The primary outcome was time to, and extent of, diagnostic testing required to confirm the presence or absence of cancer. This trial is registered at ClinicalTrials.gov, NCT04241796, and is completed. FINDINGS: Between Dec 12, 2019, and Dec 4, 2020, we recruited 6662 participants. 4204 (63·5%) of 6621 participants with analysable results were women, 2417 (36·5%) were men, and 6071 (91·7%) were White. A cancer signal was detected in 92 (1·4%) of 6621 participants with analysable results. 35 (38%) participants were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, median time to diagnostic resolution was 79 days (IQR 37-219): 57 days (33-143) in true-positive and 162 days (44-248) in false-positive participants. Most participants had both laboratory tests (26 [79%] of 33 with true-positive results and 50 [88%] of 57 with false-positive results) and imaging (30 [91%] of 33 with true-positive results and 53 [93%] of 57 with false-positive results). Fewer procedures were done in participants with false-positive results (17 [30%] of 57) than true-positive results (27 [82%] of 33) and few had surgery (one with a false-positive result and three with a true-positive result). INTERPRETATION: This study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility. FUNDING: GRAIL.


Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias , Masculino , Humanos , Femenino , Estudios Prospectivos , Detección Precoz del Cáncer , Pruebas Hematológicas , Neoplasias/diagnóstico
7.
J Plant Res ; 137(3): 307-314, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38517655

RESUMEN

The present review explains briefly the importance of phosphorus in the biological activities and states that the most phosphorus of living organisms is absorbed by plants from the soil. Next, previous studies on the mechanisms of phosphate uptake by plants are reviewed as H+-dependent or Na+-dependent co-transport systems and the phosphate environment in which plants grow is discussed. The evolution of transporter genes and their regulation mechanisms of expression is discussed in relation to the phosphorus environment.


Asunto(s)
Fosfatos , Plantas , Fosfatos/metabolismo , Plantas/metabolismo , Plantas/genética , Transporte Biológico , Fósforo/metabolismo , Suelo/química , Regulación de la Expresión Génica de las Plantas
8.
Alzheimers Dement ; 20(7): 5054-5061, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38899634

RESUMEN

INTRODUCTION: Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity. METHODS: Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO < 40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO < 50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype. RESULTS: Females with PBO < 40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity. DISCUSSION: Females who underwent PBO < 40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions. HIGHLIGHTS: Females with premenopausal bilateral oophorectomy (PBO) < 40 years had lower FA versus referents. Females with PBO < 40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.


Asunto(s)
Encéfalo , Imagen de Difusión Tensora , Ovariectomía , Premenopausia , Sustancia Blanca , Humanos , Femenino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Anisotropía
9.
Alzheimers Dement ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115941

RESUMEN

Phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences. Some sequences require the latest hardware and software system upgrades and are continuously rolled out as they become available at each site. The main sequence additions/changes in ADNI4 are: (1) compressed sensing (CS) T1-weighting, (2) pseudo-continuous arterial spin labeling (ASL) on all three vendors (GE, Siemens, Philips), (3) multiple-post-labeling-delay ASL, (4) 1 mm3 isotropic 3D fluid-attenuated inversion recovery, and (5) CS 3D T2-weighted. ADNI4 aims to help the neuroimaging community extract valuable imaging biomarkers and provide a database to test the impact of advanced imaging strategies on diagnostic accuracy and disease sensitivity among individuals lying on the cognitively normal to impaired spectrum. HIGHLIGHTS: A summary of MRI protocols for phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI 4). The design and justification for the ADNI 4 MRI protocols. Compressed sensing and multi-band advances have been applied to improve scan time. ADNI4 protocols aim to streamline safety screening and therapy monitoring. The ADNI4 database will be a valuable test bed for academic research.

10.
Alzheimers Dement ; 20(2): 1201-1213, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37932910

RESUMEN

INTRODUCTION: Cost-effective screening tools for vascular contributions to cognitive impairment and dementia (VCID) has significant implications. We evaluated non-imaging indicators of VCID using magnetic resonance imaging (MRI)-measured white matter (WM) damage and hypothesized that these indicators differ based on age. METHODS: In 745 participants from the Mayo Clinic Study of Aging (≥50 years of age) with serial WM assessments from diffusion MRI and fluid-attenuated inversion recovery (FLAIR)-MRI, we examined associations between baseline non-imaging indicators (demographics, vascular risk factors [VRFs], gait, behavioral, plasma glial fibrillary acidic protein [GFAP], and plasma neurofilament light chain [NfL]) and WM damage across three age tertiles. RESULTS: VRFs and gait were associated with diffusion changes even in low age strata. All measures (VRFs, gait, behavioral, plasma GFAP, plasma NfL) were associated with white matter hyperintensities (WMHs) but mainly in intermediate and high age strata. DISCUSSION: Non-imaging indicators of VCID were related to WM damage and may aid in screening participants and assessing outcomes for VCID. HIGHLIGHTS: Non-imaging indicators of VCID can aid in prediction of MRI-measured WM damage but their importance differed by age. Vascular risk and gait measures were associated with early VCID changes measured using diffusion MRI. Plasma markers explained variability in WMH across age strata. Most non-imaging measures explained variability in WMH and vascular WM scores in intermediate and older age groups. The framework developed here can be used to evaluate new non-imaging VCID indicators proposed in the future.


Asunto(s)
Disfunción Cognitiva , Demencia Vascular , Sustancia Blanca , Humanos , Anciano , Imagen por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen de Difusión por Resonancia Magnética/métodos , Disfunción Cognitiva/patología , Envejecimiento/patología , Demencia Vascular/patología
11.
Alzheimers Dement ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258539

RESUMEN

The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1-weighted and fluid-attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. HIGHLIGHTS: The MRI Core provides multi-platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF-fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM-SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF-fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

12.
Healthc Manage Forum ; 37(3): 156-159, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38189240

RESUMEN

Leadership is vital to a well-functioning and effective health system. This importance was underscored during the COVID-19 pandemic. As disparities in infection and mortality rates became pronounced, greater calls for equity-informed healthcare emerged. These calls led some leaders to use the Learning Health System (LHS) approach to quickly transform research into healthcare practice to mitigate inequities causing these rates. The LHS is a relatively new framework informed by many within and outside health systems, supported by decision-makers and financial arrangements and encouraged by a culture that fosters quick learning and improvements. Although studies indicate the LHS can enhance patients' health outcomes, scarce literature exists on health leaders' use and incorporation of equity into the LHS. This article begins addressing this gap by examining how equity can be incorporated into LHS activities and discussing ways leaders can ensure equity is considered and achieved in rapid learning cycles.


Asunto(s)
COVID-19 , Liderazgo , Aprendizaje del Sistema de Salud , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Equidad en Salud , Pandemias
13.
Neuroimage ; 276: 120199, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37269958

RESUMEN

It is now widely known that research brain MRI, CT, and PET images may potentially be re-identified using face recognition, and this potential can be reduced by applying face-deidentification ("de-facing") software. However, for research MRI sequences beyond T1-weighted (T1-w) and T2-FLAIR structural images, the potential for re-identification and quantitative effects of de-facing are both unknown, and the effects of de-facing T2-FLAIR are also unknown. In this work we examine these questions (where applicable) for T1-w, T2-w, T2*-w, T2-FLAIR, diffusion MRI (dMRI), functional MRI (fMRI), and arterial spin labelling (ASL) sequences. Among current-generation, vendor-product research-grade sequences, we found that 3D T1-w, T2-w, and T2-FLAIR were highly re-identifiable (96-98%). 2D T2-FLAIR and 3D multi-echo GRE (ME-GRE) were also moderately re-identifiable (44-45%), and our derived T2* from ME-GRE (comparable to a typical 2D T2*) matched at only 10%. Finally, diffusion, functional and ASL images were each minimally re-identifiable (0-8%). Applying de-facing with mri_reface version 0.3 reduced successful re-identification to ≤8%, while differential effects on popular quantitative pipelines for cortical volumes and thickness, white matter hyperintensities (WMH), and quantitative susceptibility mapping (QSM) measurements were all either comparable with or smaller than scan-rescan estimates. Consequently, high-quality de-facing software can greatly reduce the risk of re-identification for identifiable MRI sequences with only negligible effects on automated intracranial measurements. The current-generation echo-planar and spiral sequences (dMRI, fMRI, and ASL) each had minimal match rates, suggesting that they have a low risk of re-identification and can be shared without de-facing, but this conclusion should be re-evaluated if they are acquired without fat suppression, with a full-face scan coverage, or if newer developments reduce the current levels of artifacts and distortion around the face.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Neuroimagen , Artefactos , Marcadores de Spin
14.
Neuroimage ; 269: 119912, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36731814

RESUMEN

The clinical usefulness MRI biomarkers for aging and dementia studies relies on precise brain morphological measurements; however, scanner and/or protocol variations may introduce noise or bias. One approach to address this is post-acquisition scan harmonization. In this work, we evaluate deep learning (neural style transfer, CycleGAN and CGAN), histogram matching, and statistical (ComBat and LongComBat) methods. Participants who had been scanned on both GE and Siemens scanners (cross-sectional participants, known as Crossover (n = 113), and longitudinally scanned participants on both scanners (n = 454)) were used. The goal was to match GE MPRAGE (T1-weighted) scans to Siemens improved resolution MPRAGE scans. Harmonization was performed on raw native and preprocessed (resampled, affine transformed to template space) scans. Cortical thicknesses were measured using FreeSurfer (v.7.1.1). Distributions were checked using Kolmogorov-Smirnov tests. Intra-class correlation (ICC) was used to assess the degree of agreement in the Crossover datasets and annualized percent change in cortical thickness was calculated to evaluate the Longitudinal datasets. Prior to harmonization, the least agreement was found at the frontal pole (ICC = 0.72) for the raw native scans, and at caudal anterior cingulate (0.76) and frontal pole (0.54) for the preprocessed scans. Harmonization with NST, CycleGAN, and HM improved the ICCs of the preprocessed scans at the caudal anterior cingulate (>0.81) and frontal poles (>0.67). In the Longitudinal raw native scans, over- and under-estimations of cortical thickness were observed due to the changing of the scanners. ComBat matched the cortical thickness distributions throughout but was not able to increase the ICCs or remove the effects of scanner changeover in the Longitudinal datasets. CycleGAN and NST performed slightly better to address the cortical thickness variations between scanner change. However, none of the methods succeeded in harmonizing the Longitudinal dataset. CGAN was the worst performer for both datasets. In conclusion, the performance of the methods was overall similar and region dependent. Future research is needed to improve the existing approaches since none of them outperformed each other in terms of harmonizing the datasets at all ROIs. The findings of this study establish framework for future research into the scan harmonization problem.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Estudios Transversales , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Envejecimiento , Cintigrafía
15.
J Gen Intern Med ; 38(13): 2936-2944, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37429974

RESUMEN

BACKGROUND: Delirium is among the most prevalent harmful events in hospitals that is associated with an elevated risk for severe outcomes such as functional decline, falls, longer length of stay, and increased mortality. OBJECTIVE: To evaluate the impact of the implementation of a multi-component delirium program on the prevalence of delirium and the incidence of falls among patients staying on general medicine inpatient hospital units. DESIGN: A pre-post intervention study using retrospective chart abstraction and interrupted time series analysis. COHORT: Patients were selected from adult patients that stayed at least 1 day on one of the five general medicine units in a large community hospital in Ontario, Canada. A total of 16 random samples of 50 patients per month for 8 consecutive months pre-intervention (October 2017 to May 2018) and 8 months post intervention (January 2019 to August 2019) were selected for a total of 800 patients. There were no exclusion criteria. INTERVENTION: The delirium program included multiple components: education of staff and hospital leadership, twice per day bed-side screen for delirium, non-pharmacological and pharmacological prevention, and intervention strategies and a delirium consultation team. MEASUREMENT: Delirium prevalence was assessed using the evidence-based delirium chart abstraction method, CHART-del. Demographic data as well as fall incidence were also collected. RESULT: Our evaluation showed that the implementation of a multicomponent delirium program led to a reduction in delirium prevalence and fall incidences. The reduction in both delirium and falls was the largest for patients in the ages between 72 and 83 years old and varied across inpatient units. CONCLUSION: A multi-component delirium program to improve the prevention, recognition, and management of delirium reduces the prevalence of delirium and fall incidence among patients in general medicine units.


Asunto(s)
Delirio , Adulto , Humanos , Anciano , Anciano de 80 o más Años , Análisis de Series de Tiempo Interrumpido , Estudios Retrospectivos , Delirio/diagnóstico , Delirio/epidemiología , Delirio/prevención & control , Hospitales Comunitarios , Ontario , Unidades Hospitalarias
16.
Tob Control ; 32(5): 546-552, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-34911813

RESUMEN

INTRODUCTION: A common barrier identified by individuals trying to quit smoking is the cost of cessation pharmacotherapies. The purpose of this evaluation was to: (1) Assess the feasibility of offering nicotine replacement therapy (NRT) 'gift cards' to hospitalised smokers for use posthospitalisation; and, (2) Estimate the effect of providing NRT gift cards on 6-month smoking abstinence. METHODS: A prospective, quasi-experimental, before-and-after controlled cohort design with random sampling was used to compare patients who had received the Ottawa Model for Smoking Cessation (OMSC) intervention ('control') with patients who received the OMSC plus a $C300 Quit Card ('QCI'), which they could use to purchase any brand or form of NRT from any Canadian pharmacy. RESULTS: 750 Quit Cards were distributed to the three participating hospitals of which 707 (94.3%) were distributed to patients. Of the cards received by patients, 532 (75.2%) were used to purchase NRT. A total of 272 participants completed evaluation surveys (148 control; 124 QCI).Point prevalence abstinence rates adjusted for misreporting among survey responders were 15.3% higher in the QCI group, compared with controls (44.4% vs 29.1%; OR 1.95, 1.18-3.21; p=0.009). Satisfaction was high among participants in both groups, and among staff delivering the QCI. QCI participants rated the intervention as high in terms of motivation, ease of use and helpfulness. CONCLUSIONS: The NRT gift card appears to be a feasible and effective smoking cessation tool that removes a primary barrier to the use of evidence-based smoking cessation pharmacotherapies, while motivating both patients and health providers.


Asunto(s)
Cese del Hábito de Fumar , Humanos , Estudios Prospectivos , Pacientes Internos , Proyectos Piloto , Dispositivos para Dejar de Fumar Tabaco , Canadá , Encuestas y Cuestionarios , Fumar , Hospitales
17.
J Ethn Subst Abuse ; 22(3): 606-625, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34533434

RESUMEN

While Black girls have lower rates of drug use, they face worse health and wellbeing consequences associated with drug use. Understanding which strengths-based factors serve as buffers to limit adverse outcomes related to drug use among Black girls is essential for prevention. This study investigated the mediating role of sociopolitical control on drug use among Black girls (n = 340). Using path analysis, models were tested to include the variables of interest. Sociopolitical control (e.g. leadership competency and policy control) significantly mediated the relationship between ethnic identity and social support on drug use. Implications from this study may consider bolstering empowerment-based strategies in drug use prevention for Black girls.

18.
BMC Genomics ; 23(1): 574, 2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-35953768

RESUMEN

BACKGROUND: Echinoderms are established models in experimental and developmental biology, however genomic resources are still lacking for many species. Here, we present the draft genome of Ophioderma brevispinum, an emerging model organism in the field of regenerative biology. This new genomic resource provides a reference for experimental studies of regenerative mechanisms. RESULTS: We report a de novo nuclear genome assembly for the brittle star O. brevispinum and annotation facilitated by the transcriptome assembly. The final assembly is 2.68 Gb in length and contains 146,703 predicted protein-coding gene models. We also report a mitochondrial genome for this species, which is 15,831 bp in length, and contains 13 protein-coding, 22 tRNAs, and 2 rRNAs genes, respectively. In addition, 29 genes of the Notch signaling pathway are identified to illustrate the practical utility of the assembly for studies of regeneration. CONCLUSIONS: The sequenced and annotated genome of O. brevispinum presented here provides the first such resource for an ophiuroid model species. Considering the remarkable regenerative capacity of this species, this genome will be an essential resource in future research efforts on molecular mechanisms regulating regeneration.


Asunto(s)
Equinodermos , Genoma Mitocondrial , Animales , Núcleo Celular , Equinodermos/genética , Anotación de Secuencia Molecular , Regeneración/genética , Transcriptoma
19.
Neuroimage ; 251: 119020, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35196565

RESUMEN

Specific brain structures (gray matter regions and white matter tracts) play a dominant role in determining cognitive decline and explain the heterogeneity in cognitive aging. Identification of these structures is crucial for screening of older adults at risk of cognitive decline. Using deep learning models augmented with a model-interpretation technique on data from 1432 Mayo Clinic Study of Aging participants, we identified a subset of brain structures that were most predictive of individualized cognitive trajectories and indicative of cognitively resilient vs. vulnerable individuals. Specifically, these structures explained why some participants were resilient to the deleterious effects of elevated brain amyloid and poor vascular health. Of these, medial temporal lobe and fornix, reflective of age and pathology-related degeneration, and corpus callosum, reflective of inter-hemispheric disconnection, accounted for 60% of the heterogeneity explained by the most predictive structures. Our results are valuable for identifying cognitively vulnerable individuals and for developing interventions for cognitive decline.


Asunto(s)
Envejecimiento Cognitivo , Disfunción Cognitiva , Aprendizaje Profundo , Anciano , Envejecimiento/psicología , Encéfalo , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/psicología , Humanos , Imagen por Resonancia Magnética
20.
Acta Neuropathol ; 144(6): 1117-1125, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35841412

RESUMEN

Summarizing the multiplicity and heterogeneity of cerebrovascular disease (CVD) features into a single measure has been difficult in both neuropathology and imaging studies. The objective of this work was to evaluate the association between neuroimaging surrogates of CVD and two available neuropathologic CVD scales in those with both antemortem imaging CVD measures and postmortem CVD evaluation. Individuals in the Mayo Clinic Study of Aging with MRI scans within 5 years of death (N = 51) were included. Antemortem CVD measures were computed from diffusion MRI (dMRI), FLAIR, and T2* GRE imaging modalities and compared with postmortem neuropathologic findings using Kalaria and Strozyk Scales. Of all the neuroimaging measures, both regional and global dMRI measures were associated with Kalaria and Strozyk Scales (p < 0.05) and modestly correlated with global cognitive performance. The major conclusions from this study were: (i) microstructural white matter injury measurements using dMRI may be meaningful surrogates of neuropathologic CVD scales, because they aid in capturing diffuse (and early) changes to white matter and secondary neurodegeneration due to lesions; (ii) vacuolation in the corpus callosum may be associated with white matter changes measured on antemortem dMRI imaging; (iii) Alzheimer's disease neuropathologic change did not associate with neuropathologic CVD scales; and (iv) future work should be focused on developing better quantitative measures utilizing dMRI to optimally assess CVD-related neuropathologic changes.


Asunto(s)
Enfermedad de Alzheimer , Trastornos Cerebrovasculares , Sustancia Blanca , Humanos , Neuropatología , Imagen por Resonancia Magnética , Neuroimagen/métodos , Sustancia Blanca/patología , Trastornos Cerebrovasculares/complicaciones , Enfermedad de Alzheimer/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología
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