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1.
Neuropsychologia ; 204: 109000, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39271053

RESUMO

Humans can use the contents of memory to construct scenarios and events that they have not encountered before, a process colloquially known as imagination. Much of our current understanding of the neural mechanisms mediating imagination is limited by paradigms that rely on participants' subjective reports of imagined content. Here, we used a novel behavioral paradigm that was designed to systematically evaluate the contents of an individual's imagination. Participants first learned the layout of four distinct rooms containing five wall segments with differing geometrical characteristics, each associated with a unique object. During functional MRI, participants were then shown two different wall segments or objects on each trial and asked to first, retrieve the associated objects or walls, respectively (retrieval phase) and then second, imagine the two objects side-by-side or combine the two wall segments (imagination phase). Importantly, the contents of each participant's imagination were interrogated by having them make a same/different judgment about the properties of the imagined objects or scenes. Using univariate and multivariate analyses, we observed widespread activity across occipito-temporal cortex for the retrieval of objects and for the imaginative creation of scenes. Interestingly, a classifier, whether trained on the imagination or retrieval data, was able to successfully differentiate the neural patterns associated with the imagination of scenes from that of objects. Our results reveal neural differences in the cued retrieval of object and scene memoranda, demonstrate that different representations underlie the creation and/or imagination of scene and object content, and highlight a novel behavioral paradigm that can be used to systematically evaluate the contents of an individual's imagination.

2.
Proc Natl Acad Sci U S A ; 121(37): e2404250121, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39231203

RESUMO

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.


Assuntos
Citomegalovirus , Proteínas do Envelope Viral , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , Citomegalovirus/imunologia , Humanos , Animais , Camundongos , Microscopia Crioeletrônica , Conformação Proteica , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Internalização do Vírus , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Estabilidade Proteica , Vacinas contra Citomegalovirus/imunologia , Substituição de Aminoácidos , Modelos Moleculares
3.
Artigo em Inglês | MEDLINE | ID: mdl-39327863

RESUMO

OBJECTIVE: Mandibular osteoradionecrosis (MORN) is a morbid complication of head and neck radiation therapy. Recent advances in surgical and medical therapies underscore the need for a shift in traditional treatment paradigms and a disease grading system that can guide appropriate management. DATA SOURCES: Pubmed/MEDLINE. REVIEW METHODS: We conducted a detailed review of publications related to MORN, specifically focusing on its staging and management techniques. Articles meeting inclusion criteria were synthesized into a final narrative review. CONCLUSION: There has been a paradigm shift away from hyperbaric oxygen therapy in the management of MORN. Growing evidence for the efficacy of pentoxifylline and tocopherol in early-stage disease and novel surgical techniques to manage moderate and late-stage disease warrant an updated staging stratification which is proposed. IMPLICATIONS FOR PRACTICE: This review summarizes the clinical efficacy of established and novel therapeutic modalities currently available in treating MORN, emphasizing the significant advances achieved over the last decade. It introduces a contemporary staging and treatment algorithm which incorporates traditional, evidence-supported surgical and medical management with effective early intervention strategies.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39214605

RESUMO

Spaces produced in healthcare settings and research institutions tend to perpetuate marginalized populations' state of social otherness. We believe nurses from borderlands are best suited to walk between dominant (striated) spaces and margins in healthcare settings. Borderlands is a liminal space where multiple identities, places, cultures, paradigms, or ways of thinking intersect. We believe nurses can navigate these spaces by becoming walkers/travelers between worlds or as nepantleras Anzaldúa's critical rhetorical analysis framework can assist borderlands nurses to create geographies of inclusion for equity-denied groups as it is within these borderlands spaces that the dominant narratives are relegated to the margins and new spaces are imagined.

5.
Cell Rep Med ; 5(8): 101668, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39094579

RESUMO

We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Humanos , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , Epitopos/imunologia , Feminino , Anticorpos Monoclonais/imunologia , Masculino
6.
Can Fam Physician ; 70(7-8): e89-e96, 2024.
Artigo em Francês | MEDLINE | ID: mdl-39122438

RESUMO

OBJECTIF: Présenter un guide à l'intention des professionnels des soins primaires sur le dépistage approprié des infections transmissibles sexuellement (ITS) chez des patients qui s'identifient comme des hommes ayant des rapports sexuels avec des hommes (HSH). SOURCES DE L'INFORMATION: Les lignes directrices canadiennes sur le dépistage des ITS et des infections entériques et par des protozoaires; les lignes directrices ontariennes sur le dépistage du VIH et du mpox; et les lignes directrices américaines sur le dépistage des ITS. MESSAGE PRINCIPAL: Dans toutes les régions du Canada, les taux des infections bactériennes, entériques, par protozoaires et systémiques, y compris le VIH et la mpox, qui sont transmissibles sexuellement, ont augmenté de manière constante chez les HSH cisgenres et transgenres. Même si elles présentent souvent des tableaux cliniques semblables, ces infections ont diverses périodes d'incubation et requièrent des méthodes de dépistage différentes, et leur présence doit être effectivement exclue afin d'orienter le diagnostic et le traitement chez des patients qui s'identifient comme des HSH et ont des symptômes de divers problèmes de santé. Par ailleurs, les renseignements et les recommandations cliniques se trouvent souvent dans de multiples lignes directrices plutôt que dans une seule source, ce qui complique encore davantage ces rencontres cliniques. Ce document fournit une consolidation des données probantes et des recommandations sur le dépistage des ITS chez les HSH. CONCLUSION: Les approches de dépistage des ITS devraient être rigoureuses, et fondées sur les facteurs de risque signalés par le patient et sur la présentation clinique. Lorsqu'un risque d'ITS est cerné, mais que les résultats des analyses en laboratoire sont négatifs, il faudrait aussi expliquer aux HSH les recommandations entourant la répétition des tests, de même que les services de prévention du VIH, comme la prophylaxie préexposition.


Assuntos
Homossexualidade Masculina , Programas de Rastreamento , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Infecções Sexualmente Transmissíveis/diagnóstico , Programas de Rastreamento/métodos , Canadá , Infecções por HIV/diagnóstico , Guias de Prática Clínica como Assunto , Fatores de Risco , Adulto
7.
Can Fam Physician ; 70(7-8): 449-455, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39122439

RESUMO

OBJECTIVE: To provide a guide on appropriate sexually transmitted infection (STI) testing for primary care providers to use with patients who identify as men who have sex with men (MSM). SOURCES OF INFORMATION: Canadian guidelines for STI testing and enteric and protozoan infections; Ontario guidelines for HIV screening and mpox; and US guidelines for STI testing. MAIN MESSAGE: Across Canada rates of sexually transmitted bacterial, enteric, protozoan, and systemic infections-including HIV and mpox-have been steadily increasing among cisgender and transgender MSM. Despite often having similar clinical presentations, these infections have different incubation periods and testing approaches and must be ruled out effectively to guide diagnosis and treatment for MSM-identifying patients who present with symptoms of various conditions. Clinical information and screening recommendations, however, are often found in multiple guidelines rather than in a single source, thus further complicating these clinical encounters. This document provides a consolidated set of evidence and recommendations for STI testing in MSM. CONCLUSION: Testing approaches for STIs should be comprehensive and based on the patient's reported risk factors and clinical presentation. Where ongoing STI risk is identified and negative laboratory test results are received, MSM should also be counselled on recommendations for repeat screening and HIV prevention services, such as preexposure prophylaxis.


Assuntos
Homossexualidade Masculina , Programas de Rastreamento , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Infecções Sexualmente Transmissíveis/diagnóstico , Programas de Rastreamento/métodos , Canadá , Infecções por HIV/diagnóstico , Guias de Prática Clínica como Assunto , Fatores de Risco , Adulto
8.
Artigo em Inglês | MEDLINE | ID: mdl-38949954

RESUMO

Background: Treatment of Bell's palsy ranges from medical management with high-dose corticosteroids to complex facial reanimation procedures. Objective: To characterize the number of static, dynamic, and combined facial reanimation procedures for the management of Bell's palsy using a national database over time. Methods: This retrospective cohort study included patients in the 2013-2020 National Surgical Quality Improvement Project database with a postoperative diagnosis of Bell's palsy. Cases were categorized as involving only static, only dynamic, and a combination of static and dynamic procedures. Chi-square or Fisher's exact tests were performed for patient demographics, and linear regressions were created to evaluate utilization trends. Results: In total, 294 patients were identified. There was no significant difference in patient sex and comorbidities between these treatment groups. Of the 294 patients, 101 received both types of procedures, 107 received only dynamic procedures, and 86 received only static procedures. The trendlines for all treatment groups were significantly positive (B = 1.27 for both, B = 0.89 for dynamic only, and B = 1.01 for static only). Conclusion: In this study of a national surgical database, an increase in static, dynamic, and combined treatments for patients with Bell's palsy was found.

10.
Laryngoscope ; 134(11): 4514-4520, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38884344

RESUMO

OBJECTIVES: To characterize the effect of facial reanimation using masseteric nerve transfer on the masseter muscle itself, examining whether there is any demonstrable atrophy postoperatively. METHODS: Electronic medical records of adult patients who underwent facial reanimation using masseteric nerve transfer at our institution over a 15-year period were reviewed. To account for the impact of postoperative radiation, randomly selected patients who underwent radical parotidectomy without nerve transfer and received postoperative radiation served as controls in a 1:1 fashion against those who underwent masseteric nerve transfer with postoperative radiation. RESULTS: Twenty patients were identified who underwent masseteric nerve transfer and had sufficient pre- and postoperative imaging to assess masseter volume (mean age 58.2, 60% female). Of the four patients who did not receive postoperative radiation, each demonstrated masseteric atrophy on the side of their nerve transfer, with a mean reduction in masseter volume of 20.6%. The remaining 16 patients were included in the case-control analysis accounting for radiation. When compared with controls, those in the study group were found to have a statistically significant difference in atrophy (p = 0.0047) and total volume loss (p = 0.0002). The overall reduction in masseter volume in the study group was significantly higher compared with the control group, at 41.7% and 16.6%, respectively (p = 0.0001). CONCLUSION: Facial reanimation utilizing masseteric nerve transfer appears to result in atrophy of the denervated masseter when compared with the contralateral muscle. This volume deficit may lead to further facial asymmetry for patients undergoing comprehensive reanimation surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4514-4520, 2024.


Assuntos
Paralisia Facial , Músculo Masseter , Atrofia Muscular , Transferência de Nervo , Humanos , Feminino , Músculo Masseter/inervação , Músculo Masseter/diagnóstico por imagem , Músculo Masseter/patologia , Masculino , Pessoa de Meia-Idade , Transferência de Nervo/métodos , Paralisia Facial/cirurgia , Paralisia Facial/etiologia , Paralisia Facial/diagnóstico por imagem , Estudos Retrospectivos , Atrofia Muscular/etiologia , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/patologia , Adulto , Idoso , Assimetria Facial/etiologia , Assimetria Facial/cirurgia , Assimetria Facial/diagnóstico por imagem , Radiografia , Estudos de Casos e Controles , Atrofia
11.
Environ Sci Pollut Res Int ; 31(29): 42428-42444, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38877192

RESUMO

Iron and steel slags have a long history of both disposal and beneficial use in the coastal zone. Despite the large volumes of slag deposited, comprehensive assessments of potential risks associated with metal(loid) leaching from iron and steel by-products are rare for coastal systems. This study provides a national-scale overview of the 14 known slag deposits in the coastal environment of Great Britain (those within 100 m of the mean high-water mark), comprising geochemical characterisation and leaching test data (using both low and high ionic strength waters) to assess potential leaching risks. The seaward facing length of slag deposits totalled at least 76 km, and are predominantly composed of blast furnace (iron-making) slags from the early to mid-20th Century. Some of these form tidal barriers and formal coastal defence structures, but larger deposits are associated with historical coastal disposal in many former areas of iron and steel production, notably the Cumbrian coast of England. Slag deposits are dominated by melilite phases (e.g. gehlenite), with evidence of secondary mineral formation (e.g. gypsum, calcite) indicative of weathering. Leaching tests typically show lower element (e.g. Ba, V, Cr, Fe) release under seawater leaching scenarios compared to deionised water, largely ascribable to the pH buffering provided by the former. Only Mn and Mo showed elevated leaching concentrations in seawater treatments, though at modest levels (<3 mg/L and 0.01 mg/L, respectively). No significant leaching of potentially ecotoxic elements such as Cr and V (mean leachate concentrations <0.006 mg/L for both) were apparent in seawater, which micro-X-Ray Absorption Near Edge Structure (µXANES) analysis show are both present in slags in low valence (and low toxicity) forms. Although there may be physical hazards posed by extensive erosion of deposits in high-energy coastlines, the data suggest seawater leaching of coastal iron and steel slags in the UK is likely to pose minimal environmental risk.


Assuntos
Monitoramento Ambiental , Ferro , Aço , Ferro/química , Ferro/análise , Poluentes Químicos da Água/análise , Água do Mar/química
12.
Oral Maxillofac Surg Clin North Am ; 36(3): 401-409, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38724423

RESUMO

Facial nerve pathology in children has devastating functional and psychosocial consequences. Facial palsy occurs less commonly in children than adults with a greater proportion caused by congenital causes. Most pediatric patients have normal life expectancy and few comorbidities and dynamic restoration of facial expression is prioritized. This article will focus on the unique aspects of care for facial palsy in the pediatric population.


Assuntos
Doenças do Nervo Facial , Paralisia Facial , Humanos , Criança , Paralisia Facial/etiologia , Nervo Facial
13.
PLoS One ; 19(5): e0302785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768150

RESUMO

INTRODUCTION: The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. OBJECTIVES: To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. METHODOLOGY: All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. RESULTS: From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). CONCLUSION: Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Gonorreia , Neisseria gonorrhoeae , Faringe , Reto , Manejo de Espécimes , Humanos , Chlamydia trachomatis/isolamento & purificação , Chlamydia trachomatis/genética , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Gonorreia/diagnóstico , Gonorreia/microbiologia , Masculino , Neisseria gonorrhoeae/isolamento & purificação , Neisseria gonorrhoeae/genética , Reto/microbiologia , Faringe/microbiologia , Manejo de Espécimes/métodos , Adulto , Feminino , Técnicas de Amplificação de Ácido Nucleico/métodos , Homossexualidade Masculina , Pessoa de Meia-Idade , Autocuidado , Adulto Jovem
14.
Facial Plast Surg Clin North Am ; 32(2): 239-246, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575282

RESUMO

A successful nasal reconstruction relies heavily on a stable internal lining. Larger defects pose unique challenges for internal lining reconstruction as obtaining tissue of adequate size while maintaining airway patency is difficult. The prelamination technique uses a staged skin graft to the paramedian forehead flap prior to transfer. As such, a composite flap can be later transferred to reconstruct internal and external nasal defects concomitantly. This article reviews the current background, techniques, and clinical considerations in the use of the prelaminated forehead flap for nasal lining reconstruction in partial to total nasal defects.


Assuntos
Neoplasias Nasais , Rinoplastia , Humanos , Rinoplastia/métodos , Testa/cirurgia , Neoplasias Nasais/cirurgia , Nariz/cirurgia , Retalhos Cirúrgicos
15.
J Assoc Nurses AIDS Care ; 35(4): 309-324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564213

RESUMO

ABSTRACT: Clinical trials of pre-exposure prophylaxis (PrEP) to prevent HIV infection have established its efficacy as upwards of 99%. Despite this, the effectiveness of this medication has been shown to be diminished by individual factors, such as medication adherence. We completed a systematic review to identify and describe interventions to improve oral PrEP adherence. Overall, 16 articles were located. Two of the articles reported on results from the same trial and were collapsed for analysis, bringing the total to 15 studies. Twelve unique PrEP adherence interventions were tested, with the most common intervention being the use of mobile phone technology, which was used in 7 (46%) of the studies. Ten (67%) studies found that medication adherence improved when participants received an intervention to support adherence. Adherence intervention strategies effectively improved PrEP adherence. Further research into PrEP adherence interventions is warranted, particularly among diverse groups.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Profilaxia Pré-Exposição/métodos , Adesão à Medicação/psicologia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Administração Oral , Telefone Celular , Masculino
16.
AIDS Behav ; 28(6): 2015-2022, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38526637

RESUMO

Current international HIV testing guidelines recommend that HIV negative persons from HIV priority groups complete repeat screening every 3-6 months; local guidelines in our jurisdiction recommend that such retesting should occur every 3 months. Such an approach allows for timely HIV diagnosis and linkage to care - and aligns with the UNAIDS 95-95-95 targets to have 95% of undiagnosed persons be aware of their HIV status. To meet these aims, new approaches to HIV testing have been developed, including our HIV self-testing initiative, GetaKit.ca, which uses an online screening algorithm to determine eligibility and has built in pathways for re-test reminders, linkage HIV prevention care, and rapid follow-up for positive test results. To understand self-testing frequency in relation to our local recommendations for resting every 3 months, we evaluated data from participants who ordered repeat HIV self-tests through GetaKit.ca. Descriptive analyses were performed on participant characteristics and chi-square tests were performed on aggregated participant risk data. During the study period, 5235 HIV self-tests were distributed to 3627 participants, of whom, 26% ordered more than once and 27% belonged to an HIV priority population. Participants who retested were more likely to have been white, male, and part of an HIV priority population; they were also more likely to have completed prior STI or HIV testing or had a prior STI diagnosis, compared to those who did not. We identified 16 new HIV diagnoses, 2 of which were among repeat testers. Our results suggest that HIV self-testing can be useful to help meet UNAIDS targets to identify undiagnosed infections; however, such efforts are less likely to be successful without adequate linkage to follow-up services, including HIV treatment and prevention care.


Assuntos
Infecções por HIV , Teste de HIV , Programas de Rastreamento , Autoteste , Humanos , Masculino , Feminino , Adulto , Infecções por HIV/diagnóstico , Pessoa de Meia-Idade , Programas de Rastreamento/métodos , Teste de HIV/estatística & dados numéricos , Teste de HIV/métodos , Adulto Jovem , Adolescente , Algoritmos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
17.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38545622

RESUMO

We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K D < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC 50 ∼0.1-1.75 nM) and provided robust protection in vivo . Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization. HIGHLIGHTS: ▪ Infection and vaccination elicit unique IgG antibody profiles at the molecular level▪ Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)▪ Hybrid immunity maintains the imprint of first infection or first vaccination▪ Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth.

18.
Laryngoscope ; 134(8): 3548-3554, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38470307

RESUMO

OBJECTIVE: To estimate and adjust for rater effects in operating room surgical skills assessment performed using a structured rating scale for nasal septoplasty. METHODS: We analyzed survey responses from attending surgeons (raters) who supervised residents and fellows (trainees) performing nasal septoplasty in a prospective cohort study. We fit a structural equation model with the rubric item scores regressed on a latent component of skill and then fit a second model including the rating surgeon as a random effect to model a rater-effects-adjusted latent surgical skill. We validated this model against conventional measures including the level of expertise and post-graduation year (PGY) commensurate with the trainee's performance, the actual PGY of the trainee, and whether the surgical goals were achieved. RESULTS: Our dataset included 188 assessments by 7 raters and 41 trainees. The model with one latent construct for surgical skill and the rater as a random effect was the best. Rubric scores depended on how severe or lenient the rater was, sometimes almost as much as they depended on trainee skill. Rater-adjusted latent skill scores increased with attending-estimated skill levels and PGY of trainees, increased with the actual PGY, and appeared constant over different levels of achievement of surgical goals. CONCLUSION: Our work provides a method to obtain rater effect adjusted surgical skill assessments in the operating room using structured rating scales. Our method allows for the creation of standardized (i.e., rater-effects-adjusted) quantitative surgical skill benchmarks using national-level databases on trainee assessments. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:3548-3554, 2024.


Assuntos
Competência Clínica , Internato e Residência , Salas Cirúrgicas , Humanos , Salas Cirúrgicas/normas , Estudos Prospectivos , Septo Nasal/cirurgia , Rinoplastia/educação , Rinoplastia/normas , Cirurgiões/educação , Cirurgiões/normas , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Feminino , Masculino
19.
Am J Otolaryngol ; 45(4): 104262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38552339

RESUMO

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.


Assuntos
Anastomose Cirúrgica , Microcirurgia , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/instrumentação , Estudos Transversais , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Microcirurgia/instrumentação , Microcirurgia/efeitos adversos , Falha de Equipamento/estatística & dados numéricos , Estados Unidos , Trombose/etiologia , United States Food and Drug Administration , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Retalhos de Tecido Biológico/efeitos adversos , Bases de Dados Factuais
20.
PLOS Glob Public Health ; 4(2): e0002336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324519

RESUMO

COVID-19 self-testing strategy (COVIDST) can rapidly identify symptomatic and asymptomatic SARS-CoV-2-infected individuals and their contacts, potentially reducing transmission. In this living systematic review, we evaluated the evidence for real-world COVIDST performance. Two independent reviewers searched six databases (PubMed, Embase, Web of Science, World Health Organization database, Cochrane COVID-19 registry, Europe PMC) for the period April 1st, 2020, to January 18th, 2023. Data on studies evaluating COVIDST against laboratory-based conventional testing and reported on diagnostic accuracy, feasibility, acceptability, impact, and qualitative outcomes were abstracted. Bivariate random effects meta-analyses of COVIDST accuracy were performed (n = 14). Subgroup analyses (by sampling site, symptomatic/asymptomatic infection, supervised/unsupervised strategy, with/without digital supports) were conducted. Data from 70 included studies, conducted across 25 countries with a median sample size of 817 (range: 28-784,707) were pooled. Specificity and DOR was high overall, irrespective of subgroups (98.37-99.71%). Highest sensitivities were reported for: a) symptomatic individuals (73.91%, 95%CI: 68.41-78.75%; n = 9), b) mid-turbinate nasal samples (77.79%, 95%CI: 56.03-90.59%; n = 14), c) supervised strategy (86.67%, 95%CI: 59.64-96.62%; n = 13), and d) use of digital interventions (70.15%, 95%CI: 50.18-84.63%; n = 14). Lower sensitivity was attributed to absence of symptoms, errors in test conduct and absence of supervision or a digital support. We found no difference in COVIDST sensitivity between delta and omicron pre-dominant period. Digital supports increased confidence in COVIDST reporting and interpretation (n = 16). Overall acceptability was 91.0-98.7% (n = 2) with lower acceptability reported for daily self-testing (39.5-51.1%). Overall feasibility was 69.0-100.0% (n = 5) with lower feasibility (35.9-64.6%) for serial self-testing. COVIDST decreased closures in school, workplace, and social events (n = 4). COVIDST is an effective rapid screening strategy for home-, workplace- or school-based screening, for symptomatic persons, and for preventing transmission during outbreaks. These data will guide COVIDST policy. Our review demonstrates that COVIDST has paved the way for self-testing in pandemics worldwide.

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