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1.
Front Public Health ; 12: 1386714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022409

RESUMO

Introduction: Youth Participatory Action Research (YPAR) is an approach to conducting research with youth populations in order to effectively engage youth in research that impacts their lives. Young people experiencing homelessness (YEH) are vulnerable to power and social environments in ways that call attention to their experiences in research. Methods: The context for this paper was a qualitative YPAR project to incorporate youth voice into the operations of a larger research study that hired youth as researchers. Participant-researchers provided feedback and consultation with senior staff in order to improve their access to resources, safety, and stability. Results: Themes that emerged from thematic analysis of reflections, discussions, and meetings showed the need for consistent access to food, the risk of environmental violence targeting youth researchers, the structural and experiential barriers to professional engagement, and the benefits that young researchers experienced as part of their work in the study. Discussion: Recommendations and lessons learned are described, notably to ensure that youth are paid and provided food, to construct effective safety plans during fieldwork, and to provide a flexible, inclusive, trauma-responsive approach to supervision of project tasks.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Jovens em Situação de Rua , Pesquisa Qualitativa , Humanos , Adolescente , Jovens em Situação de Rua/psicologia , Feminino , Masculino , Pesquisadores/psicologia , Adulto Jovem
2.
Phys Rev Lett ; 132(26): 266601, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996300

RESUMO

Weyl fermions are hypothetical chiral particles that can also manifest as excitations near three-dimensional band crossing points in lattice systems. These quasiparticles are subject to the Nielsen-Ninomiya "no-go" theorem when placed on a lattice, requiring the total chirality across the Brillouin zone to vanish. This constraint results from the topology of the (orientable) manifold on which they exist. Here, we ask to what extent the concepts of topology and chirality of Weyl points remain well defined when the underlying manifold is nonorientable. We show that the usual notion of chirality becomes ambiguous in this setting, allowing for systems with a nonzero total chirality. This circumvention of the Nielsen-Ninomiya theorem stems from a generic discontinuity of the vector field whose zeros are Weyl points. Furthermore, we discover that Weyl points on nonorientable manifolds carry an additional Z_{2} topological invariant which satisfies a different no-go theorem. We implement such Weyl points by imposing a nonsymmorphic symmetry in the momentum space of lattice models. Finally, we experimentally realize all aspects of their phenomenology in a photonic platform with synthetic momenta. Our work highlights the subtle but crucial interplay between the topology of quasiparticles and of their underlying manifold.

3.
Mol Pain ; : 17448069241270295, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054310

RESUMO

The transmission of nociceptive and pruriceptive signals in the spinal cord is greatly influenced by descending modulation from brain areas such as the rostral ventromedial medulla (RVM). Within the RVM 3 classes of neurons have been discovered which are relevant to spinal pain modulation, the On, Off, and Neutral cells. These neurons were discovered due to their functional response to nociceptive stimulation. On cells are excited, Off cells are inhibited, and Neutral cells have no response to noxious pain stimulation. Since these neurons are identified by functional response characteristics it has been difficult to molecularly identify them. In the present study, we leverage our ability to perform optotagging within the RVM to determine whether RVM On, Off, and Neutral cells are GABAergic. We found that 27.27% of RVM On cells, 47.37% of RVM Off cells, and 42.6% of RVM Neutral cells were GABAergic. These results demonstrate that RVM On, Off, and Neutral cells represent a heterogeneous population of neurons and provide a reliable technique for the molecular identification of these neurons.

4.
J Biol Chem ; : 107560, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002681

RESUMO

Lowering expression of prion protein (PrP) is a well-validated therapeutic strategy in prion disease, but additional modalities are urgently needed. In other diseases, small molecules have proven capable of modulating pre-mRNA splicing, sometimes by forcing inclusion of cryptic exons that reduce gene expression. Here, we characterize a cryptic exon located in human PRNP's sole intron and evaluate its potential to reduce PrP expression through incorporation into the 5' untranslated region (5'UTR). This exon is homologous to exon 2 in non-primate species, but contains a start codon that would yield an upstream open reading frame (uORF) with a stop codon prior to a splice site if included in PRNP mRNA, potentially downregulating PrP expression through translational repression or nonsense-mediated decay. We establish a minigene transfection system and test a panel of splice site alterations, identifying mutants that reduce PrP expression by as much as 78%. Our findings nominate a new therapeutic target for lowering PrP.

5.
Trauma Surg Acute Care Open ; 9(1): e001403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974221

RESUMO

Background: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements. Methods: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression. Results: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively). Conclusions: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours. Level of evidence: Level II.

6.
Small ; : e2402293, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923726

RESUMO

Cobalt phthalocyanine (CoPc) is a promising molecular catalyst for aqueous electroreduction of CO2, but its catalytic activity is limited by aggregation at high loadings. Codeposition of CoPc onto electrode surfaces with the coordinating polymer poly(4-vinylpyridine) (P4VP) mitigates aggregation in addition to providing other catalytic enhancements. Transmission and diffuse reflectance UV-vis measurements demonstrate that a combination of axial coordination and π-stacking effects from pyridyl moieties in P4VP serve to disperse cobalt phthalocyanine in deposition solutions and help prevent reaggregation in deposited films. Polymers lacking axial coordination, such as Nafion, are significantly less effective at cobalt phthalocyanine dispersion in both the deposition solution and in the deposited films. SEM images corroborate these findings through particle counts and morphological analysis. Electrochemical measurements show that CoPc codeposited with P4VPonto carbon electrode surfaces reduces CO2 with higher activity and selectivity compared to the catalyst codeposited with Nafion.

7.
JAMA Netw Open ; 7(6): e2418114, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38913375

RESUMO

Importance: Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear. Objective: To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF. Design, Setting, and Participants: Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023. Exposure: VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group). Main Outcomes and Measures: The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors. Results: The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant. Conclusions and Relevance: In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.


Assuntos
Anticoagulantes , Fibrilação Atrial , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etnologia , Masculino , Feminino , Idoso , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Estados Unidos/epidemiologia , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , United States Department of Veterans Affairs , Pessoa de Meia-Idade , Varfarina/uso terapêutico , Hispânico ou Latino/estatística & dados numéricos , Idoso de 80 Anos ou mais , Etnicidade/estatística & dados numéricos , População Branca/estatística & dados numéricos
8.
Front Cell Neurosci ; 18: 1386352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841202

RESUMO

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron-glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.

9.
J Sex Res ; : 1-14, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940432

RESUMO

Humans have sex for myriad reasons, many unrelated to desire. But under what conditions does sexual desire not lead to sex? We investigated reasons college students refrain from sex despite desire and having an attractive, willing partner and relationships between these reasons and other aspects of sexuality and personality. For item generation, 604 participants identified 109 reasons why individuals may refrain from sex despite desire. For construct validation, 712 participants reported the frequency they experienced these reasons on a novel measure. Every reason evidencing discernible gender differences was endorsed more by women. These items largely concentrated in factors of Personal Insecurities and Principled Concerns. No gender differences emerged on the Partner Issues factor. Factors differentially related to sexuality and personality variables. Principled Concerns related negatively to sociosexual behavior and attitudes and positively to sexual traditionalism across genders. Partner Issues positively correlated with sociosexual behavior and desire for women. Personal Insecurities negatively correlated with sociosexual attitudes for men. Principled Concerns related to sexual functioning issues for women. Personal Insecurities and Principled Concerns related to worse sexual functioning for men. Personal Insecurities related to Neuroticism across genders. These results suggest potential directions for therapeutic interventions and further research.

10.
J Prim Care Community Health ; 15: 21501319241251934, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726652

RESUMO

INTRODUCTION/OBJECTIVES: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. PRIMARY AIM: Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. SECONDARY AIM: Evaluate associations between sociodemographics and screening adherence. METHODS: Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. RESULTS: Primary HPV uptake represented <1% of annual screening from 1/2017 to 1/2022. On 1/1/2022, only 55% of 21 to 29 year old and 63% of 30 to 65 year old were up to date with screening among the studied population. For 21 to 29 year old, compared with White women, Black women were 28% less likely to be screened [RR = 0.72 (0.66-0.79)]. Compared with never-smokers, current smokers were 9% less likely to be screened [RR = 0.91 (0.87-0.96)], past smokers were 14% more likely [RR = 1.14 (1.09-1.2)]. Among 30 to 65 year old, compared with White women, Black women were 14% less likely to be screened [RR = 0.86 (0.81-0.9)]. Compared with never-smokers, current smokers were 21% less likely to be screened [RR = 0.79 (0.77-0.81)], past smokers were 6% less likely [RR = 0.94 (0.92-0.95)]. Jointly considering race, ethnicity, smoking status, Charlson score, and rurality, findings were similar for 21 to 29 year old; Black women were screened less than White women [RR = 0.73 (0.67-0.79)]; current smokers [RR = 0.9 (0.85-0.94)] and past smokers [RR = 1.12 (1.06-1.17)] were screened less than never smokers. For 30 to 65 year old, Black women were screened less than White women [RR = 0.83 (0.79-0.88)]; current smokers [RR = 0.8 (0.78-0.81)] and past smokers [RR = 0.95 (0.93-0.96)] were screened less than never smokers. CONCLUSIONS: Screening rates remained below the Healthy People 2030 goal of 79.2% over time, particularly for younger Black women and current smokers, with minimal use of primary HPV screening.


Assuntos
Detecção Precoce de Câncer , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Detecção Precoce de Câncer/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Idoso , Meio-Oeste dos Estados Unidos/epidemiologia , Adulto Jovem , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Papillomavirus Humano
11.
Artigo em Inglês | MEDLINE | ID: mdl-38713568

RESUMO

A major challenge in applying deep learning to medical imaging is the paucity of annotated data. This study explores the use of synthetic images for data augmentation to address the challenge of limited annotated data in colonoscopy lesion classification. We demonstrate that synthetic colonoscopy images generated by Generative Adversarial Network (GAN) inversion can be used as training data to improve polyp classification performance by deep learning models. We invert pairs of images with the same label to a semantically rich and disentangled latent space and manipulate latent representations to produce new synthetic images. These synthetic images maintain the same label as the input pairs. We perform image modality translation (style transfer) between white light and narrow-band imaging (NBI). We also generate realistic synthetic lesion images by interpolating between original training images to increase the variety of lesion shapes in the training dataset. Our experiments show that GAN inversion can produce multiple colonoscopy data augmentations that improve the downstream polyp classification performance by 2.7% in F1-score and 4.9% in sensitivity over other methods, including state-of-the-art data augmentation. Testing on unseen out-of-domain data also showcased an improvement of 2.9% in F1-score and 2.7% in sensitivity. This approach outperforms other colonoscopy data augmentation techniques and does not require re-training multiple generative models. It also effectively uses information from diverse public datasets, even those not specifically designed for the targeted downstream task, resulting in strong domain generalizability. Project code and model: https://github.com/DurrLab/GAN-Inversion.

12.
Diabetes Care ; 47(7): 1171-1180, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38752923

RESUMO

OBJECTIVE: This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). RESEARCH DESIGN AND METHODS: A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). RESULTS: All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. CONCLUSIONS: This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.


Assuntos
Diabetes Mellitus Tipo 2 , Tutoria , Atenção Primária à Saúde , Humanos , Diabetes Mellitus Tipo 2/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Tutoria/métodos , Idoso , Adulto , Hemoglobinas Glicadas/metabolismo , Pessoal Técnico de Saúde
13.
Can J Microbiol ; 70(7): 289-302, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747604

RESUMO

The Grand River watershed is the largest catchment in southern Ontario. The river's northern and southern sections are influenced by agriculture, whereas central regions receive wastewater effluent and urban runoff. To characterize in-river microbial communities, as they relate to spatial and environmental factors, we conducted two same-day sampling events along the entire 300 km length of the river, representing contrasting flow seasons (high flow spring melt and low flow end of summer). Through high-throughput sequencing of 16S rRNA genes, we assessed the relationship between river microbiota and spatial and physicochemical variables. Flow season had a greater impact on communities than spatial or diel effects and profiles diverged with distance between sites under both flow conditions, but low-flow profiles exhibited higher beta diversity. High-flow profiles showed greater species richness and increased presence of soil and sediment taxa, which may relate to increased input from terrestrial sources. Total suspended solids, dissolved inorganic carbon, and distance from headwaters significantly explained microbial community variation during the low-flow event, whereas conductivity, sulfate, and nitrite were significant explanatory factors for spring melt. This study establishes a baseline for the Grand River's microbial community, serving as a foundation for modeling the microbiology of anthropogenically impacted freshwater systems affected by lotic processes.


Assuntos
Bactérias , Microbiota , RNA Ribossômico 16S , Rios , Estações do Ano , Rios/microbiologia , Ontário , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade
15.
J Prim Care Community Health ; 15: 21501319241249400, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695452

RESUMO

OBJECTIVE: The purpose of this study was to implement a 2-phase approach to rapidly increase the number of annual wellness visits (AWVs) and build a sustainable model at 3 study units (Mayo Clinic in Rochester, Minnesota, and clinics in 2 regions of Mayo Clinic Health System), which collectively serve approximately 80 000 patients who qualify for an AWV annually. METHODS: In the rapid improvement phase, beginning in July 2022, goals at the facilities were reoriented to prioritize AWVs, educate staff on existing AWV resources, and create low-effort workflows so that AWVs could be incorporated into existing patient appointments. Staff at all 3 study units worked independently and iterated quickly. In the second phase, all study units collaborated to design and implement a best-practice solution while they leveraged the engagement and lessons learned from the first phase and invested in additional system elements and change management to codify long-term success. RESULTS: The number of AWVs completed monthly increased in each study unit. In the rapid improvement phase, the number of AWVs increased but then plateaued (or decreased at some study units). In April 2023, the final scheduled outreach automation and visit tools were implemented, and the number of AWVs was sustained or increased, while outreach and scheduling times were decreased. The number of completed AWVs increased from 1148 across all study units in the first 6 months of 2022 to 14 061 during the first 6 months of 2023. CONCLUSIONS: The lessons learned from this project can be applied to other health systems that want to provide more patients with AWVs while improving operational efficiency. The keys are to have a clear vision of a successful outcome, engage all stakeholders, and iterate quickly to find what works best for the organization.


Assuntos
Promoção da Saúde , Humanos , Minnesota , Promoção da Saúde/métodos , Melhoria de Qualidade , Atenção Primária à Saúde/organização & administração , Agendamento de Consultas
16.
medRxiv ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38746398

RESUMO

Neurofilament light (NfL) concentration in cerebrospinal fluid (CSF) and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance of NfL from biofluids. We observed an NfL increase of 3.5-fold in plasma and 5.7-fold in CSF in an asymptomatic individual at risk for genetic prion disease following 6 weeks' treatment with oral minocycline for a dermatologic indication. Other biomarkers remained normal, and proteomic analysis of CSF revealed that the spike was exquisitely specific to neurofilaments. NfL dropped nearly to normal levels 5 weeks after minocycline cessation, and the individual remained free of disease 2 years later. Plasma NfL in dermatology patients was not elevated above normal controls. Dramatically high plasma NfL (>500 pg/mL) was variably observed in some hospitalized individuals receiving minocycline. In mice, treatment with minocycline resulted in variable increases of 1.3- to 4.0-fold in plasma NfL, with complete washout 2 weeks after cessation. In neuron-microglia co-cultures, minocycline increased NfL concentration in conditioned media by 3.0-fold without any visually obvious impact on neuronal health. We hypothesize that minocycline does not cause or exacerbate neuronal damage, but instead impacts the clearance of NfL from biofluids, a potential confounder for interpretation of this biomarker.

17.
Pain ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38709489

RESUMO

ABSTRACT: Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, ß-pinene, α-humulene, and ß-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the potential antinociception and mechanism of these Cannabis terpenes in a mouse model of chronic pain. We first tested for antinociception by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with mouse models of chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal antinociception to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain and identify a receptor mechanism for this activity.

18.
Nat Commun ; 15(1): 4321, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773076

RESUMO

The flat bands in magic-angle twisted bilayer graphene (MATBG) provide an especially rich arena to investigate interaction-driven ground states. While progress has been made in identifying the correlated insulators and their excitations at commensurate moiré filling factors, the spin-valley polarizations of the topological states that emerge at high magnetic field remain unknown. Here we introduce a technique based on twist-decoupled van der Waals layers that enables measurement of their electronic band structure and-by studying the backscattering between counter-propagating edge states-the determination of the relative spin polarization of their edge modes. We find that the symmetry-broken quantum Hall states that extend from the charge neutrality point in MATBG are spin unpolarized at even integer filling factors. The measurements also indicate that the correlated Chern insulator emerging from half filling of the flat valence band is spin unpolarized and suggest that its conduction band counterpart may be spin polarized.

19.
BMJ Open Sport Exerc Med ; 10(2): e001956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736641

RESUMO

Sports participation confers many health benefits yet greatly increases injury risk. Long-term health outcomes in former athletes and transition to life after competitive sports are understudied. Ending a sport may pose physical and psychosocial challenges. The purpose was to determine the lived experiences of former competitive athletes and how their sports participation impacted their long-term health and well-being. Former college varsity athletes participated in semistructured interviews focusing on their experiences, including past and current health, the impact of injuries, activity, exercise, diet and transition to life after competitive sport. Thematic analysis was completed using a collaborative, iterative process. Thirty-one (16 female, 15 male) former college athletes aged 51.3±7.4 years were interviewed. Six themes emerged: (1) lifelong athlete identity; (2) structure, support and challenges of the college athlete experience; (3) a big transition to life beyond competitive sport; (4) impact of competitive sport on long-term health; (5) facilitators and barriers to long-term health after sport and (6) transferable life skills. Continuing sports eased the transition for many but often delayed their postathlete void. Challenges included managing pain and prior injury (eg, If I didn't have my knee injury, I would definitely be more active), reducing energy needs and intake (eg, When I was an athlete, I could eat anything; and unfortunately, that's carried into my regular life), lack of accountability, changed identity and lost resources and social support. Participants suggested a programme, toolkit, mentoring or exit course to facilitate the transition. While former athletes benefit from transferrable life skills and often continue sports and exercise, they face unique challenges such as managing pain and prior injury, staying active, reducing energy intake and changing identity. Future research should develop and evaluate a toolkit, programme and other resources to facilitate life after ending competitive sports under 'normal' conditions (eg, retirement) and after a career-ending injury.

20.
Laryngoscope ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602281

RESUMO

OBJECTIVE: To determine if patient factors related to ethnicity, socioeconomic status (SES), medical comorbidities, or appointment characteristics increase the risk of missing an initial adult otolaryngology appointment. METHODS: This study is a retrospective case control study at Boston Medical Center (BMC) in Boston, Massachusetts, that took place in 2019. Patient demographic and medical comorbidity data as well as appointment characteristic data were collected and compared between those that attended their initial otolaryngology appointment versus those who missed their initial appointment. Chi-square and ANOVA tests were used to calculate differences between attendance outcomes. Multivariate analysis was used to compare the odds of missing an appointment based on various patient- and appointment-related factors. RESULTS: Patients who were more likely to miss their appointments were more often female, of lower education, disabled, not employed, Black or Hispanic, and Spanish-speaking. Spring and Fall appointments were more likely to be missed. When a multivariate regression was conducted to control for social determinants of health (SDOH) such as race, insurance status, employment, and education status, the odds of females, Spanish-speaking, students, and disabled patients missing their appointment were no longer statistically significant. CONCLUSION: A majority of patients at BMC come from lower SES backgrounds and have multiple medical comorbidities. Those who reside closer to BMC, often areas of lower average income, had higher rates of missed appointments. Interventions such as decreasing lag time, providing handicap-accessible free transportation, and increasing accessibility of telemedicine for patients could help improve attendance rates at BMC. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

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