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1.
Otolaryngol Head Neck Surg ; 170(4): 1081-1090, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38219743

RESUMO

OBJECTIVE: To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. STUDY DESIGN: Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. RESULTS: Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). CONCLUSIONS: This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias da Língua , Adulto , Humanos , Estudos de Casos e Controles , Estudos Transversais , Fatores de Risco , Processo Alveolar , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias Bucais/complicações
2.
Allergy ; 79(3): 629-642, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38186079

RESUMO

BACKGROUND: Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 and Siglec-8 are closely related mast cell (MC) receptors with broad inhibitory activity, but whose functional differences are incompletely understood. METHODS: Proteomic profiling using quantitative mass spectrometry was performed on primary mouse MCs to identify proteins associated with Siglec-6 and Siglec-8. For functional characterization, each receptor was evaluated biochemically and in ex vivo and in vivo inhibition models of IgE and non-IgE-mediated MC activation in Siglec-6- or Siglec-8-expressing transgenic mice. RESULTS: Siglec-6 and Siglec-8 were found in MCs within large complexes, interacting with 66 and 86 proteins, respectively. Strikingly, Siglec-6 and Siglec-8 interacted with a large cluster of proteins involved in IgE and non-IgE-mediated MC activation, including the high affinity IgE receptor, stem cell factor (SCF) receptor KIT/CD117, IL-4 and IL-33 receptors, and intracellular kinases LYN and JAK1. Protein interaction networks revealed Siglec-6 and Siglec-8 had overlapping yet distinct MC functions, with a potentially broader regulatory role for Siglec-6. Indeed, Siglec-6 preferentially interacted with the mature form of KIT at the cell surface, and treatment with an anti-Siglec-6 antibody significantly inhibited SCF-mediated MC activation more in comparison to targeting Siglec-8. CONCLUSION: These data demonstrate a central role for Siglec-6 and Siglec-8 in controlling MC activation through interactions with multiple activating receptors and key signaling molecules. Our findings suggest that Siglec-6 has a role distinct from that of Siglec-8 in regulating MC function and represents a distinct potential therapeutic target in mast cell-driven diseases.


Assuntos
Antígenos CD , Mastócitos , Camundongos , Animais , Antígenos CD/metabolismo , Proteômica , Camundongos Transgênicos , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Imunoglobulina E/metabolismo
3.
Front Aging Neurosci ; 15: 1221768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076542

RESUMO

Objective: The role of subjective cognitive concerns (SCC) as a diagnostic criterion for MCI remains uncertain and limits the development of a universally (or widely)-accepted MCI definition. The optimal MCI definition should define an at-risk state and accurately predict the development of incident dementia. Questions remain about operationalization of definitions of self- and informant-reported SCCs and their individual and joint associations with incident dementia. Methods: The present study included Einstein Aging Study participants who were non-Hispanic White or Black, free of dementia at enrollment, had follow-up, and completed neuropsychological tests and self-reported SCC at enrollment to determine MCI status. Informant-reported SCC at baseline were assessed via the CERAD clinical history questionnaire. Self-reported SCC were measured using the CERAD, items from the EAS Health Self-Assessment, and the single memory item from the Geriatric Depression Scale. Cox proportional hazards models examined the association of different operationalizations of SCC with Petersen and Jak/Bondi MCI definitions on the risk of dementia, further controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at specific time points for each definition, and Youden's index were calculated as an accuracy measure. Cox proportional hazards models were also used to evaluate the associations of combinations of self- and informant-reported SCC with the risk of incident dementia. Results: 91% of the sample endorsed at least one SCC. Youden's index showed that not including SCC in either Jak/Bondi or Petersen classifications had the best balance between sensitivity and specificity across follow-up. A subset of individuals with informants, on average, had a lower proportion of non-Hispanic Blacks and 94% endorsed at least one self-reported SCC. Both informant-reported and self-reported SCC were significantly associated with incident dementia. Conclusion: Our findings suggest that the SCC criterion may not improve the predictive validity for dementia when included in widely-employed definitions of MCI. Consistent with some prior research, informant-reported SCC was more related to risk of incident dementia than self-reported SCC. Given that requiring informant report as a diagnostic criterion may unintentionally exclude health disparate groups, additional consideration is needed to determine how best to utilize informant-report in MCI diagnosis.

4.
Med Educ ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655437

RESUMO

BACKGROUND: Simulation-based education (SBE) is crucial to prepare nursing students prior to their clinical learning experience. Theory-based simulation learning is increasingly important for analysing how students learn. This study describes and analyses how nursing students learn through simulation in the context of palliative care communication under a socio-material approach and explores the transfer of their knowledge and skills from simulation to clinical practice. METHODS: Twenty-seven final-year nursing students in six groups participated in two simulated scenarios, followed by a debriefing and post-clinical focus groups to capture their reflections and learning. Fourteen of them joined the post-clinical focus groups after completing their clinical placements. Video recordings of the simulation, and the audio recordings from the debriefing, and post-clinical focus groups were transcribed and coded based on the human and non-human elements that were observed. These were triangulated with data collected through team participant observations, an analysis of the existing syllabi and curriculum, and a participant mapping exercise after the simulation. These various data sources illustrate how student learning and reflections took place. RESULTS: The three themes of student learning derived from the results and analysis were (1) students' expanded learning of health care communication through a socio-material approach in the context of palliative care; 2) students' discovery of the diverse and complex relations and interactions between humans and materials and (3) students' new perspectives on health care communication and the transfer of knowledge and skills through a socio-material approach in clinical practice. CONCLUSIONS: This study highlights how SBE can be further expanded using a socio-material approach to prepare students to learn beyond standardised and cognitively driven approaches and procedures. Student learning demonstrates that SBE may develop beyond high fidelity and standardisation to leave room for emergent learning and increased awareness in learning for students and teachers to optimise learning outcomes and competence.

5.
Alzheimers Dement (Amst) ; 15(1): e12410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950700

RESUMO

Introduction: We investigated the utility of the Telephone-Montreal Cognitive Assessment (T-MoCA) to track cognition in a diverse sample from the Einstein Aging Study. Methods: Telephone and in-person MoCA data, collected annually, were used to evaluate longitudinal cognitive performance. Joint models of T-MoCA and in-person MoCA compared changes, variance, and test-retest reliability measured by intraclass correlation coefficient by racial/ethnic group. Results: There were no significant differences in baseline performance or longitudinal changes across three study waves for both MoCA formats. T-MoCA performance improved over waves 1-3 but declined afterward. Test-retest reliability was lower for the T-MoCA than for the in-person MoCA. In comparison with non-Hispanic Whites, non-Hispanic Blacks and Hispanics performed worse at baseline on both MoCA formats and showed lower correlations between T-MoCA and in-person versions. Conclusions: The T-MoCA provides valuable information on cognitive change, despite racial/ethnic disparities and practice effects. We discuss implications for health disparity populations. Highlights: We assessed the comparability of Telephone-Montreal Cognitive Assessment (T-MoCA) and in-person MoCA for tracking cognition.Changes within 3 years in T-MoCA were similar to that for the in-person MoCA.T-MoCA is subject to practice effects and shows difference in performance by race/ethnicity.Test-retest reliability of T-MoCA is lower than that for in-person MoCA.

6.
Otolaryngol Head Neck Surg ; 168(5): 970-978, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36939541

RESUMO

OBJECTIVE: To systematically review the literature to determine the prevalence and risk of the free flap and postoperative complications in scalp-free tissue reconstruction with synthetic mesh cranioplasty. DATA SOURCES: Search strategies created with a medical librarian were implemented using multiple databases in May 2021. REVIEW METHODS: Two reviewers independently performed the review, data extraction, and quality assessment. Cohort studies of patients with scalp-free tissue reconstruction with or without mesh cranioplasty were included. Studies that did not report whether mesh was used or did not separate outcomes by mesh use were excluded. The primary outcomes were free flap failure and postoperative complications. A random-effects model was used for the meta-analysis to estimate prevalence and prevalence ratios (PRs). RESULTS: A total of 28 studies and 440 cases of scalp-free tissue reconstruction were included. The pooled prevalence of free flap failures and postoperative complications in patients with mesh cranioplasty was estimated at 7% (95% confidence interval [CI], 3%-17%; p = .85, I2 = 0%) and 21% (95% CI, 14%-31%; p = .44, I2 = 0%), respectively. In a subgroup analysis, mesh cranioplasty was not associated with a significantly increased risk of free flap failure or postoperative complications when compared to cases without mesh cranioplasty; pooled PR 1.21 (95% CI, 0.50-2.88; p = .90, I2 = 0%) for free flap failure and PR 1.85 (95% CI, 0.89-3.85; p = .28, I2 = 19) for postoperative complications. CONCLUSION: Synthetic mesh cranioplasty does not significantly increase the risk of free flap compromise or postoperative complications. A higher prevalence of postoperative recipient site complications was observed in patients with mesh cranioplasty.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Crânio , Telas Cirúrgicas , Humanos , Retalhos de Tecido Biológico/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Crânio/cirurgia , Telas Cirúrgicas/efeitos adversos , Titânio , Prevalência
7.
Microsurgery ; 43(3): 205-212, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36285983

RESUMO

OBJECTIVES: Much of the literature on free tissue reconstruction in the "vessel-depleted" neck is focused on identification of vessels outside the pretreated field and data on free flap outcomes when infield microvascular anastomosis is performed remain scarce. We aim to report on free flap outcomes and recipient vessel choice in a large cohort of patients with prior radiation and neck dissection (RTND) to the ipsilateral side of vessel anastomosis. METHODS: A retrospective review was performed including patients who received head and neck free tissue transfer following prior RTND to the ipsilateral side of vessel anastomosis. Pretreatment data, free flap type, defect site, and recipient vessel choice were reported. Recipient vessel choice was stratified according to neck dissection level and prior free flap. Primary outcome was free flap survival (total failure, partial failure, success) within 30 days after surgery. RESULTS: This study included 72 free flap cases in 68 patients. Free flap success was 94.4%; one case (1.4%) resulted in total flap loss and three cases (4%) had partial flap loss. The facial (35%), external carotid (ECA) (25%), and superior thyroid arteries (16%) were the most common recipient arteries. The external jugular (EJV) (38%), facial (30%), and internal jugular veins (IJV) (15%) were the most common recipient veins. The superior thyroid artery was used less frequently with a prior level 2-3/4 neck dissection compared to a prior level 1-3/4 neck dissection (6% vs. 17%, p = 0.83). The facial artery (7% vs. 67%, p < 0.01) and vein (13% vs. 46%, p = 0.04) were used less frequently when a prior free flap with ipsilateral anastomosis was performed. The superior thyroid, ECA, IJV, and EJV were more commonly used in this subgroup. CONCLUSION: Free tissue transfer with infield microvascular anastomosis in a neck with prior RTND can be safely done with comparable outcomes to surgically naïve, non-irradiated necks.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Microcirurgia/métodos , Pescoço/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Estudos Retrospectivos
8.
Int Forum Allergy Rhinol ; 13(7): 1061-1482, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36068685

RESUMO

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.


Assuntos
Apneia Obstrutiva do Sono , Adulto , Humanos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Polissonografia/métodos , Fatores de Risco
9.
Commun Biol ; 5(1): 1226, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369358

RESUMO

Mast cells (MC) are key drivers of allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 is an immunoregulatory receptor found on MCs. While it is recognized that engaging Siglecs with antibodies mediates inhibition across immune cells, the mechanisms that govern this agonism are not understood. Here we generated Siglec-6 mAb clones (AK01 to AK18) to better understand Siglec-6-mediated agonism. Siglec-6 mAbs displayed epitope-dependent receptor internalization and inhibitory activity. We identified a Siglec-6 mAb (AK04) that required Fc-mediated interaction for receptor internalization and induced inhibition and antibody-dependent cellular phagocytosis against MCs. AK04-mediated MC inhibition required Siglec-6 immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like domains and was associated with receptor cluster formation containing inhibitory phosphatases. Treatment of humanized mice with AK04 inhibited systemic anaphylaxis with a single dose and reduced MCs with chronic dosing. Our findings suggest Siglec-6 activity is epitope dependent and highlight an agonistic Siglec-6 mAb as a potential therapeutic approach in allergic disease.


Assuntos
Antígenos CD , Mastócitos , Humanos , Camundongos , Animais , Antígenos CD/química , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Anticorpos Monoclonais/farmacologia , Epitopos
10.
JMIR Form Res ; 6(10): e40726, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36256835

RESUMO

BACKGROUND: An increasing number of mental health apps (MHapps) are being developed for youth. In addition, youth are high users of both technologies and MHapps. However, little is known about their perspectives on MHapps. MHapps might be particularly well suited to reach the youth underserved by traditional mental health resources, and incorporating their perspectives is especially critical to ensure such tools are useful to them. OBJECTIVE: The goal of this study was to develop and pilot a process for eliciting youth perspectives on MHapps in a structured and collaborative way. We also sought to generate learnings on the perspectives of Latinx youth on MHapps and their use in ways that might facilitate discovery, activation, or engagement in MHapps, especially in Latinx populations. METHODS: We created a series of focus groups consisting of 5 sessions. The groups introduced different categories of MHapps (cognitive behavioral therapy apps, mindfulness apps, and miscellaneous apps). Within each category, we selected 4 MHapps that participants chose to use for a week and provided feedback through both between-session and in-session activities. We recruited 5 youths ranging in age from 15 to 21 (mean 18, SD 2.2) years. All the participants identified as Hispanic or Latinx. After completing all 5 focus groups, the participants completed a brief questionnaire to gather their impressions of the apps they had used. RESULTS: Our focus group methodology collected detailed and diverse information about youth perspectives on MHapps. However, we did identify some aspects of our methods that were less successful at engaging the youth, such as our between-session activities. The Latinx youth in our study wanted apps that were accessible, relatable, youth centric, and simple and could be integrated with their offline lives. We also found that the mindfulness apps were viewed most favorably but that the miscellaneous and cognitive behavioral therapy apps were viewed as more impactful. CONCLUSIONS: Eliciting youth feedback on MHapps is critical if these apps are going to serve a role in supporting their mental health and well-being. We refined a process for collecting feedback from the youth and identified factors that were important to a set of Latinx youth. Future work could be broader, that is, recruit larger samples of more diverse youth, or deeper, that is, collect more information from each youth around interests, needs, barriers, or facilitators or better understand the various impacts of MHapps by using qualitative and quantitative measures. Nevertheless, this study advances the formative understanding of how the youth, particularly Latinx youth, might be viewing these tools.

11.
Nurse Educ Today ; 119: 105568, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183609

RESUMO

BACKGROUND: As palliative care increases in importance due to chronic illnesses in ageing populations, there is a need to develop primary palliative care, including patient-centred communication for nursing graduates. Simulation-based education was adopted to develop students clinical skills and communication in a safer and more controlled environment prior to their clinical practice. However curricula in palliative care and communication remain limited. The current study was to develop a simulation-based programme with clinical modelling prior to the simulation experience. Authentic case scenarios were also constructed through collaboration between the researchers and clinical colleagues in palliative care. OBJECTIVES: To explore the effects of palliative care simulation-based experience on nursing students' palliative care and caring communication. DESIGN: Mixed-methods with pre- and post-questionnaires and focus groups after the simulation-based experience. SETTINGS: A nursing school at a university in Hong Kong. PARTICIPANTS: Twenty-nine senior-year undergraduate nursing students. METHODS: Students shadowed senior nurses in a palliative clinical setting, then engaged in simulation learning with two palliative scenarios in a laboratory environment. Focus group debriefings were conducted after the simulations. RESULTS: Quantitatively, findings from the pre- and post-questionnaires revealed an improvement in the students' knowledge (t = -2.83, p = 0.02), attitudes (t = -4.21, p = 0.00), and efficacy (t = -2.07, p = 0.05) in palliative care after participating in this study. Results from the focus groups also indicated an enhancement in the students' learning of palliative care and communication. CONCLUSION: This collaborative design of palliative scenarios and clinical shallowing with senior nurses in a palliative care setting followed by simulation enhanced the students' confidence, knowledge, skills, and attitudes in palliative care and communication.


Assuntos
Bacharelado em Enfermagem , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Estudantes de Enfermagem , Humanos , Cuidados Paliativos/métodos , Bacharelado em Enfermagem/métodos , Comunicação
12.
Sci Rep ; 12(1): 17320, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243725

RESUMO

Depression during sensitive periods of social development may have consequences that extend well beyond mental health, and far into adulthood. This study compared the social functioning of adults with adolescent-onset depression (ages 10-20) to those with adult-onset depression (ages 21+). Participants were 3,360 adults (67.2% female; ages 42 ± 15) who had experienced major depression. Adult functional outcomes were marital status, divorce, number of children, years of education, employment status, household income, dependency on welfare, and obesity. Participants with depression during adolescence were less likely to get married, have children, and more likely to have lower household incomes. Depression during adolescence may be associated with broader functional outcomes that impact individuals and society, and may be mitigated through intervention and effective policy.


Assuntos
Depressão , Interação Social , Adolescente , Adulto , Criança , Depressão/epidemiologia , Escolaridade , Emprego , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Adulto Jovem
13.
Cancer Control ; 29: 10732748221109991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35839251

RESUMO

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Idoso , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Humanos , Medicare , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Estados Unidos , Neoplasias Pancreáticas
14.
Laryngoscope Investig Otolaryngol ; 7(3): 901-905, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734061

RESUMO

Objective: To describe common intraoperative and pathologic findings of atypical parathyroid tumors (APTs) and evaluate clinical outcomes in patients undergoing parathyroidectomy. Methods: In this multi-institutional retrospective case series, data were collected from patients who underwent parathyroidectomy from 2000 to 2018 from three tertiary care institutions. APTs were defined according to the AJCC eighth edition guidelines and retrospective chart review was performed to evaluate the incidence of recurrent laryngeal nerve injury, recurrence of disease, and disease-specific mortality. Results: Twenty-eight patients were identified with a histopathologic diagnosis of atypical tumor. Mean age was 56 years (range, 23-83) and 68% (19/28) were female. All patients had an initial diagnosis of primary hyperparathyroidism with 21% (6/28) exhibiting clinical loss of bone density and 32% (9/28) presenting with nephrolithiasis or renal dysfunction. Intraoperatively, 29% (8/28) required thyroid lobectomy, 29% (8/28) had gross adherence to adjacent structures and 46% (13/28) had RLN adherence. The most common pathologic finding was fibrosis 46% (13/28). Postoperative complications include RLN paresis/paralysis in 14% (4/28) and hungry bone syndrome in 7% (2/28). No patients with a diagnosis of atypical tumor developed recurrent disease, however there was one patient that had persistent disease and hypercalcemia that is being observed. There were 96% (27/28) patients alive at last follow-up, with one death unrelated to disease. Conclusion: Despite the new AJCC categorization of atypical tumors staged as Tis, we observed no recurrence of disease after resection and no disease-specific mortality. However, patients with atypical tumors may be at increased risk for recurrent laryngeal nerve injury and incomplete resection.

15.
Front Immunol ; 13: 833728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154156

RESUMO

Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec-8-mediated inhibition in primary MCs using an anti-Siglec-8 monoclonal antibody (mAb). Phospho-proteomic profiling of FcεRI-activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec-8 was found to directly interact with FcεRI signaling molecules. Siglec-8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI-induced phosphorylation events through phosphatase recruitment and interaction with FcεRIγ, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Lectinas/metabolismo , Mastócitos/imunologia , Receptores de IgE/metabolismo , Animais , Degranulação Celular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteômica , Transdução de Sinais
18.
JMIR Cardio ; 5(2): e31316, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967754

RESUMO

BACKGROUND: The health benefits of urban green space have been widely reported in the literature; however, the biological mechanisms remain unexplored, and a causal relationship cannot be established between green space exposure and cardiorespiratory health. OBJECTIVE: Our aim was to conduct a panel study using personal tracking devices to continuously collect individual exposure data from healthy Chinese adults aged 50 to 64 years living in Hong Kong. METHODS: A panel of cardiorespiratory biomarkers was tested each week for a period of 5 consecutive weeks. Data on weekly exposure to green space, air pollution, and the physical activities of individual participants were collected by personal tracking devices. The effects of green space exposure measured by the normalized difference vegetation index (NDVI) at buffer zones of 100, 250, and 500 meters on a panel of cardiorespiratory biomarkers were estimated by a generalized linear mixed-effects model, with adjustment for confounding variables of sociodemographic characteristics, exposure to air pollutants and noise, exercise, and nutrient intake. RESULTS: A total of 39 participants (mean age 56.4 years, range 50-63 years) were recruited and followed up for 5 consecutive weeks. After adjustment for sex, income, occupation, physical activities, dietary intake, noise, and air pollution, significant negative associations with the NDVI for the 250-meter buffer zone were found in total cholesterol (-21.6% per IQR increase in NDVI, 95% CI -32.7% to -10.6%), low-density lipoprotein (-14.9%, 95% CI -23.4% to -6.4%), glucose (-11.2%, 95% CI -21.9% to -0.5%), and high-sensitivity C-reactive protein (-41.3%, 95% CI -81.7% to -0.9%). Similar effect estimates were found for the 100-meter and 250-meter buffer zones. After adjustment for multiple testing, the effect estimates of glucose and high-sensitivity C-reactive protein were no longer significant. CONCLUSIONS: The health benefits of green space can be found in some metabolic and inflammatory biomarkers. Further studies are warranted to establish the causal relationship between green space and cardiorespiratory health.

19.
J Alzheimers Dis ; 83(4): 1665-1678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34420967

RESUMO

BACKGROUND: The Uniform Data Set, Version 3 Neuropsychological Battery (UDSNB3.0), from the database of the University of Washington's National Alzheimer's Coordinating Center (NACC), is widely used to characterize cognitive performance in clinical and research settings; however, norms for underrepresented community-based samples are scarce. OBJECTIVE: We compared UDSNB 3.0 test scores between the Einstein Aging Study (EAS), composed of racially/ethnically diverse, community-dwelling older adults aged≥70 and the NACC, and report normative data from the EAS. METHODS: Analyses included 225 cognitively normal EAS participants and comparable data from 5,031 NACC database participants. Linear regression models compared performance between the samples, adjusting for demographics (sex, age, education, race/ethnicity), depressive symptoms, and whether English was the first language. Linear regression models to examine demographic factors including age, sex, education and race/ethnicity as predictors for the neuropsychological tests were applied in EAS and NACC separately and were used to create a demographically adjusted z-score calculator. RESULTS: Cognitive performance across all domains was worse in the EAS than in the NACC, adjusting for age, sex, education, race/ethnicity, and depression, and the differences remained in visuo-construction, visuospatial memory, confrontation naming, visual attention/processing speed, and executive functioning after further adjusting for whether English was the first language. In both samples, non-Hispanic Whites outperformed non-Hispanic Blacks and more education was associated with better cognitive performance. CONCLUSION: Differences observed in demographic, clinical, and cognitive characteristics between the community-based EAS sample and the nationwide NACC sample suggest that separate normative data that more accurately reflect non-clinic, community-based populations should be established.


Assuntos
Envelhecimento/fisiologia , População Negra/estatística & dados numéricos , Cognição/fisiologia , Etnicidade , Testes Neuropsicológicos , População Branca/estatística & dados numéricos , Idoso , Bases de Dados Factuais , Feminino , Humanos , Vida Independente , Masculino , Testes Neuropsicológicos/normas , Testes Neuropsicológicos/estatística & dados numéricos
20.
JMIR Ment Health ; 8(2): e26715, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595449

RESUMO

BACKGROUND: People with obsessive-compulsive disorder (OCD) have faced unique challenges during the COVID-19 pandemic. Research from the first two months of the pandemic suggests that a small proportion of people with OCD experienced worsening in their OCD symptoms since the pandemic began, whereas the rest experienced either no change or an improvement in their symptoms. However, as society-level factors relating to the pandemic have evolved, the effects of the pandemic on people with OCD have likely changed as well, in complex and population-specific ways. Therefore, this study contributes to a growing body of knowledge on the impact of the COVID-19 pandemic on people and demonstrates how differences across studies might emerge when studying specific populations at specific timepoints. OBJECTIVE: This study aimed to assess how members of online OCD support communities felt the COVID-19 pandemic had affected their OCD symptoms, around 3 months after the pandemic began. METHODS: We recruited participants from online OCD support communities for our brief survey. Participants indicated how much they felt their OCD symptoms had changed since the pandemic began and how much they felt that having OCD was making it harder to deal with the pandemic. RESULTS: We collected survey data from June through August 2020 and received a total of 196 responses, some of which were partial responses. Among the nonmissing data, 65.9% (108/164) of the participants were from the United States and 90.5% (152/168) had been subjected to a stay-at-home order. In all, 92.9% (182/196) of the participants said they experienced worsening of their OCD symptoms since the pandemic began, although the extent to which their symptoms worsened differed across dimensions of OCD; notably, symmetry and completeness symptoms were less likely to have worsened than others. Moreover, 95.5% (171/179) of the participants felt that having OCD made it difficult to deal with the pandemic. CONCLUSIONS: Our study of online OCD support community members found a much higher rate of OCD symptom worsening than did other studies on people with OCD conducted during the current COVID-19 pandemic. Factors such as quarantine length, location, overlapping society-level challenges, and differing measurement and sampling choices may help to explain this difference across studies.

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