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1.
Res Vet Sci ; 173: 105279, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38704977

RESUMO

Emerging pathogens can threaten human and animal health, necessitating reliable surveillance schemes to enable preparedness. We evaluated the repeatability and reproducibility of a method developed previously during a single year at one study site. Hunter-harvested ducks and geese were sampled for avian influenza virus at three discrete locations in the UK. H5N1 highly pathogenic avian influenza (HPAIV) was detected in four species (mallard [Anas platyrhynchos], Eurasian teal [Anas crecca], Eurasian wigeon [Mareca penelope] and pink-footed goose [Anser brachyrhynchus]) across all three locations and two non-HPAIV H5N1, influenza A positive detections were made from a mallard and Eurasian wigeon at two locations. Virus was detected within 1-to-4 days of sampling at every location. Application of rapid diagnostic methods to samples collected from hunter-harvested waterfowl offers potential as an early warning system for the surveillance and monitoring of emerging and existing strains of avian influenza A viruses in key avian species.

2.
Mol Ther ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38720458

RESUMO

Injectable anticoagulants are widely used in medical procedures to prevent unwanted blood clotting. However, many lack safe, effective reversal agents. Here, we present new data on a previously described RNA origami-based, direct thrombin inhibitor (HEX01). We describe a new, fast-acting, specific, single-molecule reversal agent (antidote) and present in vivo data for the first time, including efficacy, reversibility, preliminary safety, and initial biodistribution studies. HEX01 contains multiple thrombin-binding aptamers appended on an RNA origami. It exhibits excellent anticoagulation activity in vitro and in vivo. The new single-molecule, DNA antidote (HEX02) reverses anticoagulation activity of HEX01 in human plasma within 30 seconds in vitro and functions effectively in a murine liver laceration model. Biodistribution studies of HEX01 in whole mice using ex vivo imaging show accumulated mainly in the liver over 24 hours and with 10-fold lower concentrations in the kidneys. Additionally, we show that the HEX01/HEX02 system is non-cytotoxic to epithelial cell lines and non-hemolytic in vitro. Furthermore, we found no serum cytokine response to HEX01/HEX02 in a murine model. HEX01 and HEX02 represent a safe and effective coagulation control system with a fast-acting, specific reversal agent showing promise for potential drug development.

3.
Virus Evol ; 10(1): veae027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699215

RESUMO

Since 2016, A(H5Nx) high pathogenic avian influenza (HPAI) virus of clade 2.3.4.4b has become one of the most serious global threats not only to wild and domestic birds, but also to public health. In recent years, important changes in the ecology, epidemiology, and evolution of this virus have been reported, with an unprecedented global diffusion and variety of affected birds and mammalian species. After the two consecutive and devastating epidemic waves in Europe in 2020-2021 and 2021-2022, with the second one recognized as one of the largest epidemics recorded so far, this clade has begun to circulate endemically in European wild bird populations. This study used the complete genomes of 1,956 European HPAI A(H5Nx) viruses to investigate the virus evolution during this varying epidemiological outline. We investigated the spatiotemporal patterns of A(H5Nx) virus diffusion to/from and within Europe during the 2020-2021 and 2021-2022 epidemic waves, providing evidence of ongoing changes in transmission dynamics and disease epidemiology. We demonstrated the high genetic diversity of the circulating viruses, which have undergone frequent reassortment events, providing for the first time a complete overview and a proposed nomenclature of the multiple genotypes circulating in Europe in 2020-2022. We described the emergence of a new genotype with gull adapted genes, which offered the virus the opportunity to occupy new ecological niches, driving the disease endemicity in the European wild bird population. The high propensity of the virus for reassortment, its jumps to a progressively wider number of host species, including mammals, and the rapid acquisition of adaptive mutations make the trend of virus evolution and spread difficult to predict in this unfailing evolving scenario.

4.
Emerg Microbes Infect ; : 2348521, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686548

RESUMO

AbstractA free-range organic broiler (Gallus gallus domesticus) premises in Staffordshire was infected by high pathogenicity avian influenza virus (HPAIV) H5N8 during the 2020-2021 epizootic in the United Kingdom (UK). Following initial confirmation of the infection in poultry, multiple wild bird species were seen scavenging on chicken carcasses. Detected dead wild birds were subsequently demonstrated to have been infected and succumbed to HPAIV H5N8. Initially, scavenging species, magpie (Pica pica) and raven (Corvus corax), were found dead on the premises but over the following days, buzzards (Buteo buteo) were also found dead within the local area with positive detection of HPAIV in submitted carcasses. The subacute nature of microscopic lesions within a buzzard was consistent with the timeframe of infection. Finally, a considerable number of free-living pheasants (Phasianus colchicus) were also found dead in the surrounding area, with carcasses having higher viral antigen loads compared to infected chickens. Limited virus dissemination was observed in the carcasses of the magpie, raven and buzzard. Further, an avirulent avian paramyxovirus type 1 (APMV-1) was detected within poultry samples as well as in the viscera of a magpie infected with HPAIV. Immunohistochemistry did not reveal colocalization of avian paramyxovirus antigens with lesions, supporting an avirulent APMV-1 infection. Overall, this case highlights scenarios in which bi-directional transmission of avian viral diseases between commercial and wild bird species may occur. It also underlines the importance of bio separation and reduced access when infection pressure from HPAIV is high.

5.
JAMA Neurol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619853

RESUMO

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

6.
Dev Cogn Neurosci ; 66: 101373, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574406

RESUMO

Adolescence has been hypothesized to be a critical period for the development of human association cortex and higher-order cognition. A defining feature of critical period development is a shift in the excitation: inhibition (E/I) balance of neural circuitry, however how changes in E/I may enhance cortical circuit function to support maturational improvements in cognitive capacities is not known. Harnessing ultra-high field 7 T MR spectroscopy and EEG in a large, longitudinal cohort of youth (N = 164, ages 10-32 years old, 347 neuroimaging sessions), we delineate biologically specific associations between age-related changes in excitatory glutamate and inhibitory GABA neurotransmitters and EEG-derived measures of aperiodic neural activity reflective of E/I balance in prefrontal association cortex. Specifically, we find that developmental increases in E/I balance reflected in glutamate:GABA balance are linked to changes in E/I balance assessed by the suppression of prefrontal aperiodic activity, which in turn facilitates robust improvements in working memory. These findings indicate a role for E/I-engendered changes in prefrontal signaling mechanisms in the maturation of cognitive maintenance. More broadly, this multi-modal imaging study provides evidence that human association cortex undergoes physiological changes consistent with critical period plasticity during adolescence.

7.
Neurology ; 102(9): e209323, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38626363

RESUMO

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.


Assuntos
Isquemia Encefálica , Hiperglicemia , Insulinas , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Ativador de Plasminogênio Tecidual/efeitos adversos , Glicemia , Fibrinolíticos/efeitos adversos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/complicações , Hiperglicemia/induzido quimicamente , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Insulinas/uso terapêutico
8.
Sci Transl Med ; 16(742): eadi4490, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598613

RESUMO

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.


Assuntos
Hemostáticos , Roedores , Animais , Camundongos , Suínos , Roedores/metabolismo , Distribuição Tecidual , Plaquetas/metabolismo , Hemorragia , Fibrina/química , Fibrina/metabolismo
9.
J Biomech Eng ; 146(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38529730

RESUMO

Tendinopathy is a leading cause of mobility issues. Currently, the cell-matrix interactions involved in the development of tendinopathy are not fully understood. In vitro tendon models provide a unique tool for addressing this knowledge gap as they permit fine control over biochemical, micromechanical, and structural aspects of the local environment to explore cell-matrix interactions. In this study, direct-write, near-field electrospinning of gelatin solution was implemented to fabricate micron-scale fibrous scaffolds that mimic native collagen fiber size and orientation. The stiffness of these fibrous scaffolds was found to be controllable between 1 MPa and 8 MPa using different crosslinking methods (EDC, DHT, DHT+EDC) or through altering the duration of crosslinking with EDC (1 h to 24 h). EDC crosslinking provided the greatest fiber stability, surviving up to 3 weeks in vitro. Differences in stiffness resulted in phenotypic changes for equine tenocytes with low stiffness fibers (∼1 MPa) promoting an elongated nuclear aspect ratio while those on high stiffness fibers (∼8 MPa) were rounded. High stiffness fibers resulted in the upregulation of matrix metalloproteinase (MMPs) and proteoglycans (possible indicators for tendinopathy) relative to low stiffness fibers. These results demonstrate the feasibility of direct-written gelatin scaffolds as tendon in vitro models and provide evidence that matrix mechanical properties may be crucial factors in cell-matrix interactions during tendinopathy formation.


Assuntos
Gelatina , Tenócitos , Alicerces Teciduais , Gelatina/química , Animais , Cavalos , Tenócitos/citologia , Tenócitos/metabolismo , Alicerces Teciduais/química , Fenômenos Mecânicos , Regulação da Expressão Gênica , Forma Celular , Fenômenos Biomecânicos
10.
Health Serv Res ; 59(3): e14297, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38456362

RESUMO

OBJECTIVE: To identify characteristics associated with unfulfilled contraceptive preferences, document reasons for these unfulfilled preferences, and examine how these unfulfilled preferences vary across specific method users. DATA SOURCES AND STUDY SETTING: We draw on secondary baseline data from 4660 reproductive-aged contraceptive users in the Arizona, Iowa, New Jersey, and Wisconsin Surveys of Women (SoWs), state-representative surveys fielded between October 2018 and August 2020 across the four states. STUDY DESIGN: This is an observational cross-sectional study, which examined associations between individuals' reproductive health-related experiences and contraceptive preferences, adjusting for sociodemographic characteristics. Our primary outcome of interest is having an unfulfilled contraceptive preference, and a key independent variable is experience of high-quality contraceptive care. We also examine specific contraceptive method preferences according to current method used, as well as reasons for not using a preferred method. DATA COLLECTION/EXTRACTION METHODS: Survey respondents who indicated use of any contraceptive method within the last 3 months prior to the survey were eligible for inclusion in this analysis. PRINCIPAL FINDINGS: Overall, 23% reported preferring to use a method other than their current method, ranging from 17% in Iowa to 26% in New Jersey. Young age (18-24), using methods not requiring provider involvement, and not receiving quality contraceptive care were key attributes associated with unfulfilled contraceptive preferences. Those using emergency contraception and fertility awareness-based methods had some of the highest levels of unfulfilled contraceptive preferences, while pills, condoms, partner vasectomy, and IUDs were identified as the most preferred methods. Reasons for not using preferred contraceptive methods fell largely into one of two buckets: system-level or interpersonal/individual reasons. CONCLUSIONS: Our findings highlight that avenues for decreasing the gap between contraceptive methods used and those preferred to be used may lie with healthcare providers and funding streams that support the delivery of contraceptive care.


Assuntos
Comportamento Contraceptivo , Anticoncepção , Humanos , Feminino , Estudos Transversais , Adulto , Comportamento Contraceptivo/estatística & dados numéricos , Adolescente , Anticoncepção/estatística & dados numéricos , Adulto Jovem , Preferência do Paciente/estatística & dados numéricos , Pessoa de Meia-Idade , Serviços de Planejamento Familiar/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários
11.
J Stud Aff Res Pract ; 61(1): 86-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504868

RESUMO

Given the prevalence of alcohol and cannabis co-use among college students, prevention for co-use is crucial. We examined hypothetical receptiveness to substance-specific interventions among students who reported co-use. Students who use alcohol and cannabis were more receptive to alcohol interventions than cannabis interventions. Campus prevention experts should consider offering evidence-based alcohol-focused interventions as a potential pathway for decreasing substance use among college students who engage in co-use.

13.
Appl Nurs Res ; 75: 151764, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38490795

RESUMO

AIM: The purpose of this manuscript is to report the findings of a qualitative content analysis of interviews with VA Nurse Scientists about work life experiences, barriers, and facilitators across the enterprise. BACKGROUND: The VA enterprise is widely variable in terms of size, services, research activity, and budget. For this reason, the roles of nurses with a research-focused doctorate are also quite diverse. METHODS: We purposively sampled 18 PhD prepared Nurse Scientists based on a variety geographic locations, titles, and years in the field and who conduct research. We conducted semi-structured interviews over the virtual platform, WebEx. Interviews, averaging 1 h in length, were conducted between April and May 2021. We analyzed interviews using deductive and inductive content analysis. RESULTS: We found five key factors affecting VA Nurse Scientists. Each factor emerged as an important issue influencing whether Nurse Scientists reported being successful, supported, and productive in their research. These include having: 1) mentorship, 2) supportive leadership 3) available resources, 4) respect and understanding from clinical and research colleagues who understand a Nurse Scientist's role in research, and 5) a career pathway. CONCLUSIONS: VA Nurse Scientists are leaders and innovators who generate evidence to improve health outcomes and promote equity in health and health care of Veterans, their families, and caregivers. Results from this project suggest that many Nurse Scientists need additional mentorship, resources, and networks to advance their development, increase their funding success, and maximize the impact of their role, ultimately enhancing care of Veterans and their families.


Assuntos
Saúde dos Veteranos , Veteranos , Humanos , Papel do Profissional de Enfermagem , Pesquisa Qualitativa
14.
Clin Imaging ; 108: 110114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460253

RESUMO

BACKGROUND: While there are clear guidelines regarding chest wall ultrasound in the symptomatic patient, there is conflicting evidence regarding the use of ultrasound in the screening of women post-mastectomy. OBJECTIVE: To assess the utility of screening chest wall ultrasound after mastectomy and to assess features of detected malignancies. METHODS: This IRB approved, retrospective study evaluates screening US examinations of the chest wall after mastectomy. Asymptomatic women presenting for screening chest wall ultrasound from January 2016 through May 2017 were included. Cases of known active malignancy were excluded. All patients had at least one year of clinical or imaging follow-up. 43 exams (8.5 %) were performed with a history of contralateral malignancy, 465 exams (91.3 %) were performed with a history of ipsilateral malignancy, and one exam (0.2 %) was performed in a patient with bilateral prophylactic mastectomy. RESULTS: During the 17-month period, there were 509 screening US in 389 mastectomy patients. 504 (99.0 %) exams were negative/benign. Five exams (1.0 %) were considered suspicious, with recommendation for biopsy, which was performed. Out of 509 exams, 3 (0.6 %) yielded benign results, while 2 (0.39 %) revealed recurrent malignancy, with a 95 % confidence interval (exact binomial) of 0.05 % to 1.41 % for screening ultrasound. Both patients who recurred had previously recurred, and both had initial cancer of lobular histology. CONCLUSION: Of 509 chest wall screening US exams performed in mastectomy, 2 malignancies were detected, and each patient had history of invasive lobular carcinoma and at least one prior recurrence prior to this study, suggesting benefit of screening ultrasound in these populations.


Assuntos
Neoplasias da Mama , Parede Torácica , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia , Parede Torácica/diagnóstico por imagem , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia
15.
Wound Repair Regen ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459905

RESUMO

Cells integrate many mechanical and chemical cues to drive cell signalling responses. Because of the complex nature and interdependency of alterations in extracellular matrix (ECM) composition, ligand density, mechanics, and cellular responses it is difficult to tease out individual and combinatorial contributions of these various factors in driving cell behavior in homeostasis and disease. Tuning of material viscous and elastic properties, and ligand densities, in combinatorial fashions would enhance our understanding of how cells process complex signals. For example, it is known that increased ECM mechanics and transforming growth factor beta (TGF-ß) receptor (TGF-ß-R) spacing/clustering independently drive TGF-ß signalling and associated myofibroblastic differentiation. However, it remains unknown how these inputs orthogonally contribute to cellular outcomes. Here, we describe the development of a novel material platform that combines microgel thin films with controllable viscoelastic properties and DNA origami to probe how viscoelastic properties and nanoscale spacing of TGF-ß-Rs contribute to TGF-ß signalling and myofibroblastic differentiation. We found that highly viscous materials with non-fixed TGF-ß-R spacing promoted increased TGF-ß signalling and myofibroblastic differentiation. This is likely due to the ability of cells to better cluster receptors on these surfaces. These results provide insight into the contribution of substrate properties and receptor localisation on downstream signalling. Future studies allow for exploration into other receptor-mediated processes.

16.
Vaccine ; 42(9): 2347-2356, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38443277

RESUMO

Human immunodeficiency virus (HIV) infects and depletes CD4+ T-cells, resulting in Acquired Immunodeficiency Syndrome (AIDS) and death. Despite numerous clinical trials, there is no licensed HIV vaccine. The HIV envelope glycoprotein (env) is a major target for vaccine development, especially for the development of antibody-mediated protection. In this study, we used J paramyxovirus (JPV) as a viral vector to express HIV-env. We replaced the JPV small hydrophobic (SH) gene with HIV-env (rJPV-env). Intranasal rJPV-env immunization induced anti-HIV-gp120 IgG antibodies in mice. Furthermore, we examined the immunogenicity of homologous and heterologous prime/boost regimens with rJPV-env, parainfluenza virus 5 (rPIV5)-vectored HIV-env, and HIV-Gag-Env virus-like particles (VLPs). The rJPV-env/rPIV5-env heterologous prime/boost regimen induced the strongest humoral and cellular responses. Introducing a third dose of immunization, mice that received a viral-vectored prime had high levels of HIV-env-specific cellular responses, with group rJPV-env/rPIV5-env/VLP having the highest. Together, this work indicates that a heterologous combination of viral-vectored HIV-env vaccines and a HIV-Gag-Env VLP induces high levels of humoral and cellular responses against HIV in mice.


Assuntos
Vacinas contra a AIDS , Infecções por HIV , HIV-1 , Humanos , Animais , Camundongos , Vetores Genéticos , Linfócitos T , Anticorpos Anti-HIV , Infecções por HIV/prevenção & controle
17.
Spine (Phila Pa 1976) ; 49(11): 763-771, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38343165

RESUMO

STUDY DESIGN: Prospective, case series. OBJECTIVE: To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH. BACKGROUND: Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations. METHODS: A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH. RESULTS: Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH ( P <0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects ( P =0.001), L4/L5 superior endplate defects ( P =0.012), and L4/L5 inferior endplate defects ( P =0.020) on MRI. No other differences in MRI phenotypes ( e.g. Modic changes, osteophytes, etc .) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH. CONCLUSIONS: Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected. LEVEL OF EVIDENCE: Level 3.


Assuntos
Deslocamento do Disco Intervertebral , Vértebras Lombares , Imageamento por Ressonância Magnética , Fenótipo , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Vértebras Lombares/diagnóstico por imagem , Adulto , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Idoso
18.
Cogn Neurosci ; : 1-15, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38368598

RESUMO

According to the traditional memory-systems view, the hippocampus is critical during explicit (conscious) long-term memory, whereas other brain regions support implicit (nonconscious) memory. In the last two decades, some fMRI studies have reported hippocampal activity during implicit memory tasks. The aim of the present discussion paper was to identify whether any implicit memory fMRI studies have provided convincing evidence that the hippocampus is associated with nonconscious processes without being confounded by conscious processes. Experimental protocol and analysis parameters included the stimulus type(s), task(s), measures of subjective awareness, explicit memory accuracy, the relevant fMRI contrast(s) or analysis, and confound(s). A systematic review was conducted to identify implicit memory studies that reported fMRI activity in the hippocampus. After applying exclusion criteria, 13 articles remained for analysis. We found that there were no implicit memory fMRI studies where subjective awareness was absent, explicit memory performance was at chance, and there were no confounds that could have driven the observed hippocampal activity. The confounds included explicit memory (including false memory), imbalanced attentional states between conditions (yielding activation of the default-mode network), imbalanced stimuli between conditions, and differential novelty. As such, not a single fMRI study provided convincing evidence that implicit memory was associated with the hippocampus. Neuropsychological evidence was also considered, and implicit memory deficits were caused by factors known to disrupt brain regions beyond the hippocampus, such that the behavioral effects could not be attributed to this region. The present results indicate that implicit memory is not associated with the hippocampus.

19.
J Behav Med ; 47(3): 483-491, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38393445

RESUMO

Pre-surgical psychological evaluations (PSPE) are required by many insurance companies and used to help identify risk factors that may compromise bariatric post-surgical outcomes. These evaluations, however, are not yet standardized. The present study investigated the utility of a semi-structured assessment, Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), on post-surgical outcomes across 18 months. A total of 272 adult patients underwent a psychosocial evaluation and received bariatric surgery November 2017 to September 2020 at a Midwestern academic medical center. Average age at pre-surgical evaluation was 45.2 (SD = 10.7) years and 82.3% of patients were female (n = 224). With an a priori α of 0.05, multi-level modeling with weight as the outcome and regression with complications as the outcome were used. Higher SIPAT Patient Readiness, indicating difficulty with adhering to health behaviors and a reduced understanding of bariatric surgery, was associated with elevated patient weight at the 18-month follow-up (𝛽 = 0.129, p = 0.03). Higher SIPAT Social Support, was associated with patient weight at the 18-month follow-up, with reduced support associated with greater weight (𝛽 = 0.254, p = 0.004). Higher SIPAT Social Support also was associated with a greater risk of complications across the 18-month follow-up window (𝛽 = -0.108, p = 0.05). Patients with higher readiness to adhere to behavioral changes, and those reporting an intact social support system, generally weighed less at 18 months. The SIPAT may be considered as part of the standardized pre-surgical assessment, however, further research is required to elucidate its utility.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Adulto , Humanos , Feminino , Masculino , Fatores de Risco
20.
Nutr J ; 23(1): 25, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414001

RESUMO

BACKGROUND: Studies investigating the relationship between food insecurity and sleep among older populations are limited. This study aimed to cross-sectionally examine the associations between food sufficiency status and sleep outcomes in a nationally representative sample of older adults. METHODS: Our study included 1,665 older adults (≥ 65 years), using data from the 2013 and 2014 National Health and Aging Trends Study (NHATS). Food insufficiency was determined via participants' experience and utilization of food assistance programs (FAP). Sleep outcomes, including nighttime and total sleep hours, sleep latency, and sleep quality, were derived from self-reported data. Multivariable linear regression and logistic regression models were used to estimate the associations between food sufficiency status and sleep outcomes. RESULTS: In 2013-2014, 86.1% of older adults were classified as food sufficient without FAP, 9.85% as food sufficient with FAP, and 4.08% as food insufficient. Adjusting for sociodemographic characteristics, food sufficient older adults with FAP reported more total sleep hours (𝛽 = 0.31, 95% CI: -0.02, 0.64) than those participants who are food sufficient without FAP. Further adjusting for health factors, food sufficient participants with FAP had more nighttime sleep hours and greater total sleep hours compared to those participants food sufficient without FAP. Compared to those deemed as food sufficient without FAP, food sufficient participants with FAP had lower odds of having longer sleep latency (OR = 0.50, 95% CI: 0.28, 0.89), after further adjusting for physical function performance. CONCLUSIONS: Among older adults, food sufficiency with FAP is associated with greater total sleep hours, greater nighttime sleep hours, and lower odds of longer sleep latency. Our findings may help inform nutrition food assistance programs targeting older populations.


Assuntos
Estado Nutricional , Sono , Humanos , Idoso , Alimentos , Autorrelato , Envelhecimento
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