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1.
Environ Pollut ; 357: 124414, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908677

RESUMO

Plastic pollution has reached concerning levels globally, with single-use plastic products (SUPs) comprising at least 50% of plastic waste. This study investigates the physical and chemical degradation of frequently used SUPs, including petroleum-based and bio-based plastics, in natural Northern European coastal weather and marine environments over a three-year period from 2019 to 2022. Addressing a critical knowledge gap, this research was based on a hypothesis that real-world ageing studies on SUPs would produce more accurate time- and process-lines for their transformation from macro-to microplastics than are available today based on the modeling studies more frequently used. The study employs optical examination, mechanical testing, Fourier Transform Infrared (FTIR) spectroscopy, and Gas Chromatography-Mass Spectrometry (GC-MS) to determine and relate physical and chemical changes with time. The results indicate that SUPs undergo significantly faster degradation in natural weather than predicted to date. Photooxidation emerges as the primary degradation pathway for all SUPs, emphasizing the role of light in plastic breakdown. Importantly, physical degradation to microplastics in natural environments is not always associated with significant chemical changes such as breaking chemical bonds. Black SUPs exhibit greater resistance to visible light and ultraviolet radiation than equivalent white and transparent examples. In marine environments, SUPs degrade measurably slower than in air, their degradation slowing with increasing distance from the water surface. Our findings indicate the urgent need for strategies that mitigate the impacts of photo-oxidation of SUPs. Such strategies may include a focus on the removal of post-use SUPs from pavements, roads, beaches, and water surfaces where photo-oxidation is faster than underwater and underground. Preferential use of black SUPs over white or transparent should also be considered.

2.
Cogn Emot ; : 1-17, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625561

RESUMO

Despite the salient experience of encoding threatening events, these memories are prone to distortions and often non-veridical from encoding to recall. Further, threat has been shown to preferentially disrupt the binding of event details and enhance goal-relevant information. While extensive work has characterised distinctive features of emotional memory, research has not fully explored the influence threat has on temporal memory, a process putatively supported by the binding of event details into a temporal context. Two primary competing hypotheses have been proposed; that threat can impair or enhance temporal memory. We analysed two datasets to assess temporal memory for an in-person haunted house experience. In study 1, we examined the temporal structure of memory by characterising memory contiguity in free recall as a function of individual levels of heart rate as a proxy of threat. In study 2, we replicated marginal findings of threat-related increases in memory contiguity found in study 1. We extended these findings by showing threat-related increases in recency discriminations, an explicit test of temporal memory. Together, these findings demonstrate that threat enhances temporal memory regarding free recall structure and during explicit memory judgments.

3.
medRxiv ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38496628

RESUMO

Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

4.
J Orthop Case Rep ; 14(2): 82-87, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38420247

RESUMO

Introduction: Peri-implant fractures (PIF) reported after cannulated screw and dynamic hip screw fixation historically occur distal to the implant within the subtrochanteric region secondary to the development of a stress riser. Newer implant designs for femoral neck fractures have attempted to combine the benefits of minimally invasive techniques without forgoing rigid angular stability but bring new potential complications. Case Report: We present a case of an intertrochanteric PIF in the setting of a non-displaced femoral neck fracture treated with the DePuy Synthes Femoral Neck System (FNS). Conclusion: We present this case of a unique PIF pattern with the hope of identifying a potential complication associated with the novel FNS. Furthermore, we present a successful treatment option avoiding the need for conversion to hemiarthroplasty.

5.
medRxiv ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38076828

RESUMO

Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation, and may inform better selection of species for pre-clinical models.

6.
iScience ; 26(7): 107202, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37485375

RESUMO

We sought to study the role of circulating cellular clusters (CCC) -such as circulating leukocyte clusters (CLCs), platelet-leukocyte aggregates (PLA), and platelet-erythrocyte aggregates (PEA)- in the immunothrombotic state induced by COVID-19. Forty-six blood samples from 37 COVID-19 patients and 12 samples from healthy controls were analyzed with imaging flow cytometry. Patients with COVID-19 had significantly higher levels of PEAs (p value<0.001) and PLAs (p value = 0.015) compared to healthy controls. Among COVID-19 patients, CLCs were correlated with thrombotic complications (p value = 0.016), vasopressor need (p value = 0.033), acute kidney injury (p value = 0.027), and pneumonia (p value = 0.036), whereas PEAs were associated with positive bacterial cultures (p value = 0.033). In predictive in silico simulations, CLCs were more likely to result in microcirculatory obstruction at low flow velocities (≤1 mm/s) and at higher branching angles. Further studies on the cellular component of hyperinflammatory prothrombotic states may lead to the identification of novel biomarkers and drug targets for inflammation-related thrombosis.

7.
Am J Pharm Educ ; 87(12): 100542, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37419703

RESUMO

Core organizational values are essential for any organization, including academic institutions. Formal and informal leaders can have a positive, or negative, impact on shaping their culture through the core values. Members of an organization, including students, can be shaped by the organizational values in ways that strengthen, or impede, their professional identity formation. Here, we discuss the use of organizational values as vital substrates needed to shape the desired behaviors and attitudes that will help describe the organizational culture and identity. We define and discuss various types of core values, identify the benefits and challenges of core values alignment, and offer strategies for leaders at all levels to reflect on their own organization's core values and their current approach to their contribution to an effective and sustainable workplace that supports the professional identity formation of all members.


Assuntos
Educação em Farmácia , Identificação Social , Humanos , Cultura Organizacional , Estudantes
8.
Macromol Biosci ; 23(11): e2300226, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37364159

RESUMO

Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108-15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11-modified fibers significantly support NG108-15 neuronal cell and Schwann cell viability. NG108-15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost-effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration.


Assuntos
Silanos , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Células de Schwann , Nervos Periféricos , Regeneração Nervosa
9.
J Comp Eff Res ; : e220208, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37144744

RESUMO

Aim: Determine the clinical utility and economic differences over a 90-day period between robotic arm-assisted total hip arthroplasty (RATHA) and manual total hip arthroplasty (MTHA). Methods: Leveraging a nationwide commercial payer database, pre-covid THA procedures were identified. Following a 1:5 propensity score match, 1732 RATHA and 8660 MTHA patients were analyzed. Index costs, index lengths of-stay, and 90-day episode-of-care utilization and costs were evaluated. Results: Episode of care costs for RATHA was found to be $1573 lower compared with MTHA (p < 0.0001). Post-index hospital utilization was significantly less likely to occur for RATHA compared with MTHA. Total index costs were also significantly lower for RATHA versus MTHA (p < 0.0001). Conclusion: Index and post-index EOC hospital utilization and costs were lower for RATHA compared with MTHA.

10.
Sci Rep ; 13(1): 8678, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248283

RESUMO

Single-photon defect emitters (SPEs), especially those with magnetically and optically addressable spin states, in technologically mature wide bandgap semiconductors are attractive for realizing integrated platforms for quantum applications. Broadening of the zero phonon line (ZPL) caused by dephasing in solid state SPEs limits the indistinguishability of the emitted photons. Dephasing also limits the use of defect states in quantum information processing, sensing, and metrology. In most defect emitters, such as those in SiC and diamond, interaction with low-energy acoustic phonons determines the temperature dependence of the dephasing rate and the resulting broadening of the ZPL with the temperature obeys a power law. GaN hosts bright and stable single-photon emitters in the 600-700 nm wavelength range with strong ZPLs even at room temperature. In this work, we study the temperature dependence of the ZPL spectra of GaN SPEs integrated with solid immersion lenses with the goal of understanding the relevant dephasing mechanisms. At temperatures below ~ 50 K, the ZPL lineshape is found to be Gaussian and the ZPL linewidth is temperature independent and dominated by spectral diffusion. Above ~ 50 K, the linewidth increases monotonically with the temperature and the lineshape evolves into a Lorentzian. Quite remarkably, the temperature dependence of the linewidth does not follow a power law. We propose a model in which dephasing caused by absorption/emission of optical phonons in an elastic Raman process determines the temperature dependence of the lineshape and the linewidth. Our model explains the temperature dependence of the ZPL linewidth and lineshape in the entire 10-270 K temperature range explored in this work. The ~ 19 meV optical phonon energy extracted by fitting the model to the data matches remarkably well the ~ 18 meV zone center energy of the lowest optical phonon band ([Formula: see text]) in GaN. Our work sheds light on the mechanisms responsible for linewidth broadening in GaN SPEs. Since a low energy optical phonon band ([Formula: see text]) is a feature of most group III-V nitrides with a wurtzite crystal structure, including hBN and AlN, we expect our proposed mechanism to play an important role in defect emitters in these materials as well.

11.
J Comp Eff Res ; 12(6): e230025, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37212790

RESUMO

Aim: This largest-of-its-kind study evaluated the clinical utility of CA125 and OVA1, commonly used as ovarian tumor markers for assessing the risk of malignancy. The research focused on the ability and utility of these tests to reliably predict patients at low risk for ovarian cancer. Clinical utility endpoints were 12-month maintenance of benign mass status, reduction in gynecologic oncologist referral, avoidable surgical intervention and associated cost savings. Materials & methods: This was a multicenter retrospective review of data from electronic medical records and administrative claims databases. Patients receiving a CA125 or OVA1 test between October 2018 and September 2020 were identified and followed for 12 months using site-specific electronic medical records to assess tumor status and utilization outcomes. Propensity score adjustment was used to control for confounding variables. Payer allowed amounts from Merative MarketScan Research Databases were used to estimate 12-month episode-of-care costs per patient, including surgery and other interventions. Results: Among 290 low-risk OVA1 patients, 99.0% remained benign for 12 months compared with 97.2% of 181 low-risk CA125 patients. The OVA1 cohort exhibited 75% lower odds of surgical intervention in the overall sample of patients (Adjusted OR: 0.251, p ≤ 0.0001), and 63% lower odds of gynecologic oncologist utilization among premenopausal women (Adjusted OR: 0.37, p = 0.0390) versus CA125. OVA1 demonstrated significant savings in surgical interventions ($2486, p ≤ 0.0001) and total episode-of-care costs ($2621, p ≤ 0.0001) versus CA125. Conclusion: This study underscores the utility of a reliably predictive multivariate assay for assessing ovarian cancer risk. For patients assessed at low risk of ovarian tumor malignancy, OVA1 is associated with a significant reduction in avoidable surgeries and substantial cost savings per patient. OVA1 is also associated with a significant reduction in subspecialty referrals for low-risk premenopausal patients.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Risco , Estudos Retrospectivos , Biomarcadores Tumorais , Algoritmos
12.
Adv Colloid Interface Sci ; 314: 102866, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36898186

RESUMO

Peptide amphiphiles (PAs) are peptide-based molecules that contain a peptide sequence as a head group covalently conjugated to a hydrophobic segment, such as lipid tails. They can self-assemble into well-ordered supramolecular nanostructures such as micelles, vesicles, twisted ribbons and nanofibers. In addition, the diversity of natural amino acids gives the possibility to produce PAs with different sequences. These properties along with their biocompatibility, biodegradability and a high resemblance to native extracellular matrix (ECM) have resulted in PAs being considered as ideal scaffold materials for tissue engineering (TE) applications. This review introduces the 20 natural canonical amino acids as building blocks followed by highlighting the three categories of PAs: amphiphilic peptides, lipidated peptide amphiphiles and supramolecular peptide amphiphile conjugates, as well as their design rules that dictate the peptide self-assembly process. Furthermore, 3D bio-fabrication strategies of PAs hydrogels are discussed and the recent advances of PA-based scaffolds in TE with the emphasis on bone, cartilage and neural tissue regeneration both in vitro and in vivo are considered. Finally, future prospects and challenges are discussed.


Assuntos
Nanofibras , Nanoestruturas , Engenharia Tecidual , Peptídeos/química , Nanoestruturas/química , Nanofibras/química , Hidrogéis
13.
ACS Biomater Sci Eng ; 9(3): 1472-1485, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36848250

RESUMO

The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current "gold standard" of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30-50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances. A novel blend of PHAs, P(3HO)/P(3HB) (50:50), was investigated for its potential as an intraluminal aligned fiber guidance scaffold. Aligned fibers of 5 and 8 µm diameter were manufactured by electrospinning and characterized using SEM. Fibers were investigated for their effect on neuronal cell differentiation, Schwann cell phenotype, and cell viability in vitro. Overall, P(3HO)/P(3HB) (50:50) fibers supported higher neuronal and Schwann cell adhesion compared to PCL fibers. The 5 µm PHA blend fibers also supported significantly higher DRG neurite outgrowth and Schwann cell migration distance using a 3D ex vivo nerve injury model.


Assuntos
Traumatismos dos Nervos Periféricos , Traumatismos dos Nervos Periféricos/terapia , Células de Schwann/citologia , Adesão Celular , Poli-Hidroxialcanoatos/química , Elétrons , Animais , Camundongos , Células Cultivadas , Movimento Celular
14.
Neuropsychologia ; 180: 108467, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36610494

RESUMO

As individuals navigate the world, they are bound to have emotionally intense experiences. These events not only influence momentary physiological and affective responses, but may also have a powerful impact on one's memory for their emotional experience. In this research, we used the naturalistic context of a haunted house to examine how physiological arousal is associated with metacognitive emotional memory (i.e., the extent to which an individual remembers having experienced a certain emotion). Participants first navigated the haunted house while heart rate and explicit situational appraisals were recorded, and then recalled specific events from the haunted house and the intensity of these affective events approximately one week later. We found that heart rate predicted both the intensity of reported scariness in the haunted house and meta-cognitive memory of affect during recall. Critically, we found evidence for malleability in metacognitive emotional memory based on how the event was initially labeled. Individuals tended to recall events that they explicitly labeled as fear-evoking as being more intense than they reported at the time of the event. We found the opposite relationship for events that they labeled as not fear-evoking. Taken together, this indicates that there are strong relationships between physiological arousal and emotional experiences in naturalistic contexts, but that affective labeling can modulate the relationship between these features when reflecting on the emotionality of that experience in memory.


Assuntos
Metacognição , Humanos , Emoções/fisiologia , Rememoração Mental/fisiologia , Frequência Cardíaca , Nível de Alerta/fisiologia
15.
J Funct Biomater ; 14(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36662087

RESUMO

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used.

16.
J Knee Surg ; 36(10): 1077-1086, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35817055

RESUMO

In this observational, retrospective study, we performed economic analyses between robotic arm-assisted total knee arthroplasty (RATKA) and manual total knee arthroplasty (MTKA). Specifically, we compared: (1) index costs including computed tomography (CT) scans; (2) 90-day postoperative health care utilization, (3) 90-day episode-of-care (EOC) costs, and (4) lengths of stay between CT scan-based robotically-assisted versus MTKAs. A large national database, Blue Health Intelligence (BHI), was used for RATKAs and MTKAs performed between April 1, 2017 and September 30, 2019. Based on strict inclusion-exclusion criteria, with propensity score matching, 4,135 RATKAs and 4,135 MTKAs were identified and analyzed. Index costs to the payer for RATKA patients were found to be less than those for MTKA patients ($29,984 vs. $31,280, p <0.0001). Overall, 90-day EOC costs for RATKA patients were found to be less than that for MTKA patients in the inpatient and outpatient settings. This also holds true for the use of skilled nursing facilities, pharmacies, or other services. In conclusion, the results from our study show that RATKA were associated with lower costs than MTKAs, even when including the cost of CT scans. These results are of marked importance given the emphasis to contain and reduce health care costs.


Assuntos
Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Custos de Cuidados de Saúde , Tomografia Computadorizada por Raios X , Articulação do Joelho/cirurgia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38239429

RESUMO

Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular Leishmania upon exposure to pentavalent antimonials (SbV). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed ex vivo to L. V. panamensis infection and SbV, and transcriptomes were generated. Seven metallothionein (MT) genes, potent scavengers of heavy metals and central elements of the mammalian cell machinery for xenobiotic detoxification, were within the top 20 up-regulated genes. To functionally validate the participation of MTs in drug-mediated killing of intracellular Leishmania, tandem knockdown (KD) of MT2-A and MT1-E, MT1-F, and MT1-X was performed using a pan-MT shRNA approach in THP-1 cells. Parasite survival was unaffected in tandem-KD cells, as a consequence of strong transcriptional upregulation of MTs by infection and SbV, overcoming the KD effect. Gene silencing of the metal transcription factor-1 (MTF-1) abrogated expression of MT1 and MT2-A genes, but not ZnT-1. Upon exposure to SbV, intracellular survival of Leishmania in MTF-1KD cells was significantly enhanced. Results from this study highlight the participation of macrophage MTs in Sb-dependent parasite killing.

18.
Mar Pollut Bull ; 184: 114128, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36130424

RESUMO

Polyurethane (PUR) ether sponges represent a widely-used cleaning tool with a short service lifetime resulting in the production of high quantities of waste. However, the fate of PUR in natural environments is poorly understood. In this study, sponges were exposed to the natural environments of Danish weather and seawater for two years. Physiochemical changes were monitored using visual, microscopic, spectroscopic and chromatographic techniques. Results from Attenuated Total Reflection-Fourier Transform Infrared spectroscopy and change in mass indicated that photo-oxidation was the primary degradation pathway of polyurethane ether- based sponges with a specific surface degradation rate of 12,500 µm year-1 in Danish weather. Significantly, analysis by gas chromatography-mass spectrometry showed the release to the environment of toxic substance TDI as a product of photo-oxidation. Although PUR degraded more slowly in seawater than in weather, flame retardant TMCP leached from sponges to water, indicating potential health risks of PUR waste to aquatic life.


Assuntos
Retardadores de Chama , Poliuretanos , Poliuretanos/química , Éteres , Tempo (Meteorologia) , Água , Dinamarca
19.
J Neurosci ; 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879096

RESUMO

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

20.
Virulence ; 13(1): 890-902, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35587156

RESUMO

Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Humanos , Projetos Piloto , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus
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