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1.
Nature ; 574(7779): 553-558, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645721

RESUMO

Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing1, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing2,3. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has implications for regenerative medicine and rejuvenation strategies4. Here we show that fibroblast cultures from old mice secrete inflammatory cytokines and exhibit increased variability in the efficiency of iPS cell reprogramming between mice. Variability between individuals is emerging as a feature of old age5-8, but the underlying mechanisms remain unknown. To identify drivers of this variability, we performed multi-omics profiling of fibroblast cultures from young and old mice that have different reprogramming efficiencies. This approach revealed that fibroblast cultures from old mice contain 'activated fibroblasts' that secrete inflammatory cytokines, and that the proportion of activated fibroblasts in a culture correlates with the reprogramming efficiency of that culture. Experiments in which conditioned medium was swapped between cultures showed that extrinsic factors secreted by activated fibroblasts underlie part of the variability between mice in reprogramming efficiency, and we have identified inflammatory cytokines, including TNF, as key contributors. Notably, old mice also exhibited variability in wound healing rate in vivo. Single-cell RNA-sequencing analysis identified distinct subpopulations of fibroblasts with different cytokine expression and signalling in the wounds of old mice with slow versus fast healing rates. Hence, a shift in fibroblast composition, and the ratio of inflammatory cytokines that they secrete, may drive the variability between mice in reprogramming in vitro and influence wound healing rate in vivo. This variability may reflect distinct stochastic ageing trajectories between individuals, and could help in developing personalized strategies to improve iPS cell generation and wound healing in elderly individuals.


Assuntos
Envelhecimento/metabolismo , Reprogramação Celular , Senescência Celular/fisiologia , Fibroblastos/metabolismo , Cicatrização , Animais , Linhagem Celular , Reprogramação Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mediadores da Inflamação/metabolismo , Judeus/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Processos Estocásticos , Fatores de Tempo , Cicatrização/efeitos dos fármacos
2.
Am J Transplant ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996969

RESUMO

Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human IgG1 monoclonal antibody that binds the major capsid protein VP1 of BKPyV with picomolar affinity, neutralizes infection by the four major BKPyV genotypes (EC50 ranging from 0.009 to 0.093 µg/ml; EC90 ranging from 0.102 to 4.160 µg/ml), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified three key contact residues in VP1 (Y169, R170, K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were Grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease.

3.
Retina ; 44(5): 868-877, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38170761

RESUMO

PURPOSE: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria. METHODS: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease. RESULTS: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone. CONCLUSION: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.


Assuntos
Doenças Autoimunes , Angiofluoresceinografia , Doenças Retinianas , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Idoso , Tomografia de Coerência Óptica/métodos , Doenças Autoimunes/diagnóstico , Angiofluoresceinografia/métodos , Idoso de 80 Anos ou mais , Doenças Retinianas/diagnóstico , Doenças Retinianas/fisiopatologia , Fundo de Olho
4.
Med Teach ; 45(5): 466-474, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35868011

RESUMO

Neuroanatomy is a complex and fascinating subject that is often a daunting prospect for medical students. In fact, the fear of learning neuroanatomy has gained its own name - "neurophobia." This widespread phenomenon among medical students poses a challenge to medical teachers and educators. To tackle "neurophobia" by summarising tips for dynamic and engaging neuroanatomy teaching formulated based on our experiences as medical students and evidence-based techniques.Focusing on the anatomical, physiological, and clinical aspects of neurology and their integration, here we present 12 tips which are [1] Teach the basic structure before fine details, [2] Supplement teaching with annotated diagrams, [3] Use dissections for haptic learning, [4] Teach form and function together, [5] Group anatomy into systems, [6] Familiarise students with neuroimaging, [7] Teach from clinical cases, [8] Let the patient become the teacher, [9] Build from first principles, [10] Try working in reverse, [11] Let the student become the teacher, [12] Let the student become the examiner. These 12 tips can be used by teachers and students alike to provide a high-yield learning experience.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Neuroanatomia/educação , Currículo , Educação de Graduação em Medicina/métodos , Aprendizagem , Ensino
5.
Facial Plast Surg ; 39(6): 674-678, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37328152

RESUMO

Rhinoplasty is one of the most performed elective surgeries, and given the opioid crisis, increasing research and studies are focused on successful pain control with multimodality opioid-sparing techniques, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and gabapentin. Although limiting overuse of opioids is critical, this cannot be at the expense of inadequate pain control, particularly as insufficient pain control can be correlated with patient dissatisfaction and the postoperative experience in elective surgery. There is likely significant opioid overprescription, as patients often report taking less than 50% of their prescribed opioids. Furthermore, excess opioids provide opportunities for misuse and opioid diversion if not disposed of properly. To optimize postoperative pain control and minimize opioid requirements, interventions must occur at the preoperative, intraoperative, and postoperative time points. Preoperative counseling is imperative to set expectations for pain and to screen for predisposing factors for opioid misuse. Intraoperatively, use of local nerve blocks and long-acting analgesia in conjunction with modified surgical techniques can lead to prolonged pain control. Postoperatively, pain should be managed with a multimodal approach, incorporating acetaminophen, NSAIDs, and potentially gabapentin with opioids reserved for rescue analgesia. Rhinoplasty represents a category of short-stay, low/medium pain, and elective procedures highly susceptible to overprescription and consequently, are readily amenable to opioid minimization through standardized perioperative interventions. Recent literature on regimens and interventions to help limit opioids after rhinoplasty are reviewed and discussed here.


Assuntos
Analgésicos Opioides , Rinoplastia , Humanos , Analgésicos Opioides/uso terapêutico , Acetaminofen/uso terapêutico , Gabapentina/uso terapêutico , Rinoplastia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico
6.
Retina ; 41(11): 2269-2277, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34190725

RESUMO

PURPOSE: To describe characteristics and outcomes of patients with retinopathy of prematurity who failed intravitreal antivascular endothelial growth factor. METHODS: A retrospective case series of 211 eyes (112 patients) treated with antivascular endothelial growth factor as initial therapy for retinopathy of prematurity at a single academic institution between 2011 and 2019 and an additional 6 eyes (3 patients) referred to us for management of failed antivascular endothelial growth factor. RESULTS: Among the 211 eyes receiving initial treatment at our institution, 17 eyes (11%) failed. Of the 23 total eyes managed by us for failure, 3 eyes (13%) failed after 50-week postmenstrual age. Failure manifested as recurrent plus in 14 eyes (58%), recurrent Stage 3 in 13 eyes (54%) and retinal detachment in 5 eyes (21%). Treatment failures were managed with laser (13 eyes), repeat injection (4 eyes), vitrectomy (2 eyes), or a combination of modalities (4 eyes). Follow-up of ≥6 months was available for 18 of the 23 eyes. The retina was fully attached in 17 eyes, and fixation behavior was present in 10 eyes. CONCLUSION: The most common manifestations of treatment failure were recurrent plus and Stage 3. The failure rate at our institution was 11.0%. A significant proportion of failures occurred after 50-week postmenstrual age. Most failed eyes had favorable anatomical outcomes and over half demonstrated fixation behavior.


Assuntos
Bevacizumab/administração & dosagem , Ranibizumab/administração & dosagem , Retina/diagnóstico por imagem , Retinopatia da Prematuridade/tratamento farmacológico , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Idade Gestacional , Humanos , Recém-Nascido , Injeções Intravítreas , Masculino , Retinopatia da Prematuridade/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
7.
Chem Senses ; 45(4): 321-330, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32406505

RESUMO

The ability to identify odors predicts morbidity, mortality, and quality of life. It varies by age, gender, and race and is used in the vast majority of survey and clinical literature. However, odor identification relies heavily on cognition. Other facets of olfaction, such as odor sensitivity, have a smaller cognitive component. Whether odor sensitivity also varies by these factors has not been definitively answered. We analyzed data from the National Social Life, Health, and Aging Project, a nationally representative study of older US adults (n = 2081). Odor identification was measured using 5 validated odors presented with Sniffin' Stick pens as was odor sensitivity in a 6-dilution n-butanol constant stimuli detection test. Multivariate ordinal logistic regression modeled relationships between olfaction and age, gender, race, cognition, education, socioeconomic status, social network characteristics, and physical and mental health. Odor sensitivity was worse in older adults (P < 0.01), without gender (P = 0.56) or race (P = 0.79) differences. Odor identification was also worse in older adults, particularly men (both P ≤ 0.01), without differences by race. Decreased cognitive function was associated with worse odor identification (P ≤ 0.01) but this relationship was weaker for odor sensitivity (P = 0.02) in analyses that adjusted for other covariates. Odor sensitivity was less strongly correlated with cognitive ability than odor identification, confirming that it may be a more specific measure of peripheral olfactory processing. Investigators interested in associations between olfaction and health should consider both odor sensitivity and identification when attempting to understand underlying neurosensory mechanisms.


Assuntos
Cognição , Odorantes , Fatores Etários , Idoso , Estudos Transversais , Fatores Econômicos , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Raciais , Fatores Sexuais , Olfato , Rede Social , Inquéritos e Questionários , Estados Unidos
8.
Med Care ; 57(12): 937-944, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567862

RESUMO

BACKGROUND: Asian American Pacific Islander (AAPI) sexual and gender minorities (SGM) face unique challenges in mental health and accessing high-quality health care. OBJECTIVE: The objective of this study was to identify barriers and facilitators for shared decision making (SDM) between AAPI SGM and providers, especially surrounding mental health. RESEARCH DESIGN: Interviews, focus groups, and surveys. SUBJECTS: AAPI SGM interviewees in Chicago (n=20) and San Francisco (n=20). Two focus groups (n=10) in San Francisco. MEASURES: Participants were asked open-ended questions about their health care experiences and how their identities impacted these encounters. Follow-up probes explored SDM and mental health. Participants were also surveyed about attitudes towards SGM disclosure and preferences about providers. Transcripts were analyzed for themes and a conceptual model was developed. RESULTS: Our conceptual model elucidates the patient, provider, and encounter-centered factors that feed into SDM for AAPI SGM. Some participants shared the stigma of SGM identities and mental health in their AAPI families. Their AAPI and SGM identities were intertwined in affecting mental health. Some providers inappropriately controlled the visibility of the patient's identities, ignoring or overemphasizing them. Participants varied on whether they preferred a provider of the same race, and how prominently their AAPI and/or SGM identities affected SDM. CONCLUSIONS: Providers should understand identity-specific challenges for AAPI SGM to engage in SDM. Providers should self-educate about AAPI and SGM history and intracommunity heterogeneity before the encounter, create a safe environment conducive to patient disclosure of SGM identity, and ask questions about patient priorities for the visit, pronouns, and mental health.


Assuntos
Asiático/psicologia , Tomada de Decisão Compartilhada , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Participação do Paciente/psicologia , Minorias Sexuais e de Gênero/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Saúde Mental , Estigma Social
9.
Ophthalmic Plast Reconstr Surg ; 35(5): 447-450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844916

RESUMO

PURPOSE: To quantify the complete dimensions of the retro-orbicularis oculi fat (ROOF) pad and to determine its relationship to other fat compartments of the forehead. METHODS: The entire forehead of 14 hemifaces of seven fresh frozen human cadavers (four female, three male) was dissected in the subcutaneous and submuscular planes. For each plane, a ruler was placed at the facial midline, and images of the dissection plane were taken at 90° and 45°. Images were analyzed for vertical height, horizontal length, the distance to midline from the point of maximal height, and area for each hemiface of the ROOF and for the entire fat compartment contiguous with the ROOF. A two-tailed t test was conducted between ROOF and ROOF plus the extended fat plane across all measurements. A Wilcoxon nonparametric signed rank test was performed to determine equivalent fat distribution of the extended fat plane over each cadaver's respective eye. RESULTS: The deep fat originating from the ROOF consistently extended laterally and superiorly in each specimen, distinctly separated via septae from the deep central, deep lateral, and the deep temporal fat compartments. The color, composition, and distribution of this contiguous deep fat did not differ phenotypically from the traditional ROOF. The extended deep fat plane possessed an average vertical height of 3.09 ± 0.68 cm, average distance to midline from point of maximal height of 3.56 ± 0.53 cm, an average horizontal length of 5.37 ± 0.82 cm, and an average area of 13.40 ± 2.69 cm. The extended deep fat demonstrated a statistically significant increase in maximal height, length, and total area compared with the ROOF. A Wilcoxon nonparametric signed rank test was nonsignificant (α = 0.01) across all measurements, demonstrating that the extended fat plane was similarly distributed over each eye. CONCLUSIONS: A layer of deep fat originating from the traditionally defined ROOF extends superiorly and laterally beneath the frontalis muscle, separate from the deep lateral, deep central, and deep temporal fat pads. This is the first study to clearly demonstrate a contiguous superficial musculoaponeurotic system layer of fat extending under both the orbicularis oculi and frontalis muscles. This plane of fat is more appropriately described as the retro-orbicularis oculi and frontalis fat.


Assuntos
Tecido Adiposo/anatomia & histologia , Pálpebras/anatomia & histologia , Músculos Faciais/anatomia & histologia , Músculos Oculomotores/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
J Biol Chem ; 292(11): 4743-4752, 2017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28174303

RESUMO

The precise signaling mechanisms by which type II IFN receptors control expression of unique genes to induce biological responses remain to be established. We provide evidence that Sin1, a known element of the mammalian target of rapamycin complex 2 (mTORC2), is required for IFNγ-induced phosphorylation and activation of AKT and that such activation mediates downstream regulation of mTORC1 and its effectors. These events play important roles in the assembly of the eukaryotic translation initiation factor 4F (eIF4F) and mRNA translation of IFN-stimulated genes. Interestingly, IFNγ-induced tyrosine phosphorylation of STAT1 is reduced in cells with targeted disruption of Sin1, leading to decreased transcription of several IFNγ-inducible genes in an mTORC2-independent manner. Additionally, our studies establish that Sin1 is essential for generation of type II IFN-dependent antiviral effects and antiproliferative responses in normal and malignant hematopoiesis. Together, our findings establish an important role for Sin1 in both transcription and translation of IFN-stimulated genes and type II IFN-mediated biological responses, involving both mTORC2-dependent and -independent functions.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas de Transporte/imunologia , Interferon gama/imunologia , Animais , Linhagem Celular , Humanos , Imunidade Inata , Camundongos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/química , Proteínas Proto-Oncogênicas c-akt/imunologia , Fator de Transcrição STAT1/química , Fator de Transcrição STAT1/imunologia , Transdução de Sinais
11.
J Pediatr ; 196: 116-122.e3, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29398049

RESUMO

OBJECTIVE: To determine how parents of infants in the neonatal intensive care unit with a poor or uncertain prognosis view their experience, and whether they view their choices as "worth it," regardless of outcome. STUDY DESIGN: Parents of eligible neonates at 2 institutions underwent audiotaped, semistructured interviews while their infants were still in the hospital and then again 6 months to 1 year after discharge or death. Interviews were transcribed and data were analyzed using thematic analysis. Two authors independently reviewed and coded each interview and discrepancies were resolved by consensus. RESULTS: Twenty-six families were interviewed in the initial group and 17 families were interviewed in the follow-up group. The most common themes identified included realism about death (24 families), appreciation for the infant's care team (23 families), and optimism and hope (22 families). Overall themes were very similar across both centers, and among parents of infants who died and those who survived. Themes of regret, futility, distrust of care team, and infant pain were brought up infrequently or not at all. CONCLUSIONS: No family believed that the care being provided to their infant was futile; rather, parents were grateful for the care provided to their infant, regardless of outcome. Even in the case of a poor prognosis or the death of an infant, families in our study viewed their infant's stay in the neonatal intensive care unit favorably.


Assuntos
Tomada de Decisões , Unidades de Terapia Intensiva Neonatal , Pais , Relações Profissional-Família , Morte , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Terapia Intensiva Neonatal , Estudos Longitudinais , Masculino , Otimismo , Alta do Paciente , Prognóstico , Pesquisa Qualitativa , Risco , Estresse Psicológico
12.
J Gen Intern Med ; 31(6): 677-87, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27008649

RESUMO

BACKGROUND: Enhancing patient-centered care and shared decision making (SDM) has become a national priority as a means of engaging patients in their care, improving treatment adherence, and enhancing health outcomes. Relatively little is known about the healthcare experiences or shared decision making among racial/ethnic minorities who also identify as being LGBT. The purpose of this paper is to understand how race, sexual orientation and gender identity can simultaneously influence SDM among African-American LGBT persons, and to propose a model of SDM between such patients and their healthcare providers. METHODS: We reviewed key constructs necessary for understanding SDM among African-American LGBT persons, which guided our systematic literature review. Eligible studies for the review included English-language studies of adults (≥ 19 y/o) in North America, with a focus on LGBT persons who were African-American/black (i.e., > 50 % of the study population) or included sub-analyses by sexual orientation/gender identity and race. We searched PubMed, CINAHL, ProQuest Dissertations & Theses, PsycINFO, and Scopus databases using MESH terms and keywords related to shared decision making, communication quality (e.g., trust, bias), African-Americans, and LGBT persons. Additional references were identified by manual reviews of peer-reviewed journals' tables of contents and key papers' references. RESULTS: We identified 2298 abstracts, three of which met the inclusion criteria. Of the included studies, one was cross-sectional and two were qualitative; one study involved transgender women (91 % minorities, 65 % of whom were African-Americans), and two involved African-American men who have sex with men (MSM). All of the studies focused on HIV infection. Sexual orientation and gender identity were patient-reported factors that negatively impacted patient/provider relationships and SDM. Engaging in SDM helped some patients overcome normative beliefs about clinical encounters. In this paper, we present a conceptual model for understanding SDM in African-American LGBT persons, wherein multiple systems of social stratification (e.g., race, gender, sexual orientation) influence patient and provider perceptions, behaviors, and shared decision making. DISCUSSION: Few studies exist that explore SDM among African-American LGBT persons, and no interventions were identified in our systematic review. Thus, we are unable to draw conclusions about the effect size of SDM among this population on health outcomes. Qualitative work suggests that race, sexual orientation and gender work collectively to enhance perceptions of discrimination and decrease SDM among African-American LGBT persons. More research is needed to obtain a comprehensive understanding of shared decision making and subsequent health outcomes among African-Americans along the entire spectrum of gender and sexual orientation.


Assuntos
Negro ou Afro-Americano/psicologia , Tomada de Decisões , Modelos Psicológicos , Participação do Paciente , Minorias Sexuais e de Gênero/psicologia , Identidade de Gênero , Disparidades nos Níveis de Saúde , Humanos , Grupos Minoritários/psicologia , Assistência Centrada no Paciente , Relações Médico-Paciente
13.
bioRxiv ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38979361

RESUMO

Tightly coordinated cell cycle regulation is essential for homeostasis. G 0 , or quiescence, is especially crucial for cells to respond to extracellular stimuli. Little is known about the mechanisms that establish the G 0 program, though the primary cilium (a key signaling hub formed only in G 0 ) is the most widely recognized marker. The study of ciliogenesis is challenging due to its small size, relative to the cell body. To address this gap in our understanding, we developed STAMP (Spatio-Temporal Analysis via Microscopy and Proteomics) to temporally map the changes in cellular landscape occurring in G 0 and ciliogenesis. Using synchronized RPE cells, we used fixed and live cell imaging combined with phosphoproteomics to uncover new signals and order them in these processes, which also allows further, more targeted, analyses (e.g., using genetic and pharmacological perturbations). We propose that STAMP is broadly applicable for studying temporal-spatial signaling processes and the underlying mechanisms in various biological contexts and cell types.

14.
Otolaryngol Head Neck Surg ; 170(1): 284-288, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37668169

RESUMO

Reputation score has been shown to be the strongest predictor of ranking in the US News & World Reports (USNWR) Best Hospitals report. However, the extent to which physicians participate in the underlying USNWR reputation survey is not well-characterized. We conducted a retrospective cross-sectional study of USNWR public methodology reports from 2015 to 2023 to characterize trends in physician response rates by specialty, region, and Doximity membership. Overall response rates declined between 2015 (24.0%) and 2023 (8.9%). In 2023, rates ranged from 4.7% (psychiatry) to 13.9% (otolaryngology). Otolaryngology had the highest response rate among all specialties between 2017 and 2023. Within otolaryngology, both response rates (25.0% to 13.9%) and count (2106 to 1724 physicians) declined between 2015 and 2023. Among Doximity members, response rates were consistently higher for otolaryngologists in the Northeast and Midwest compared to other regions. Though hospital rankings often influence where patients seek care, our findings suggest USNWR reputation scores may not be reliable or representative.


Assuntos
Medicina , Otolaringologia , Humanos , Estados Unidos , Estudos Transversais , Estudos Retrospectivos , Hospitais
15.
Laryngoscope ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973594

RESUMO

Although outcomes account for 45% of the total ranking score in otolaryngology in the 2023-2024 U.S. News Best Hospitals rankings, little attention has been paid to the representativeness of their outcomes or volume analyses. Through retrospective review of finance data from an academic otolaryngology department, we found the overall 2023-2024 USNWR volume estimate accounted for only 10.0% (n = 2, usw 024/20,334) of all adult admissions and outpatient procedures and did not adequately represent the overall case mix or caseload.

16.
Nat Aging ; 4(4): 546-567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553564

RESUMO

Partial reprogramming (pulsed expression of reprogramming transcription factors) improves the function of several tissues in old mice. However, it remains largely unknown how partial reprogramming impacts the old brain. Here we use single-cell transcriptomics to systematically examine how partial reprogramming influences the subventricular zone neurogenic niche in aged mouse brains. Whole-body partial reprogramming mainly improves neuroblasts (cells committed to give rise to new neurons) in the old neurogenic niche, restoring neuroblast proportion to more youthful levels. Interestingly, targeting partial reprogramming specifically to the neurogenic niche also boosts the proportion of neuroblasts and their precursors (neural stem cells) in old mice and improves several molecular signatures of aging, suggesting that the beneficial effects of reprogramming are niche intrinsic. In old neural stem cell cultures, partial reprogramming cell autonomously restores the proportion of neuroblasts during differentiation and blunts some age-related transcriptomic changes. Importantly, partial reprogramming improves the production of new neurons in vitro and in old brains. Our work suggests that partial reprogramming could be used to rejuvenate the neurogenic niche and counter brain decline in old individuals.


Assuntos
Células-Tronco Neurais , Neurônios , Camundongos , Animais , Neurogênese/genética , Diferenciação Celular/genética , Reprogramação Celular/genética
17.
J Vitreoretin Dis ; 7(6): 504-509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37974918

RESUMO

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

18.
Laryngoscope ; 133(2): 235-236, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36420797

RESUMO

Using publicly available Medicare data, we performed a retrospective cross-sectional analysis of separation between otolaryngologists and affiliated medical groups between 2014 and 2021. During this period, the cumulative turnover rate among otolaryngologists was 36.4%, with annual turnover rates ranging between 6.2%-10.2%. Otolaryngologist turnover rates varied by career stage and group size.


Assuntos
Otolaringologia , Médicos , Idoso , Humanos , Estados Unidos , Otorrinolaringologistas , Estudos Retrospectivos , Estudos Transversais , Medicare
19.
Laryngoscope ; 133(12): 3319-3326, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37114661

RESUMO

OBJECTIVE: To identify the impact of gender on the clinical outcomes of endoscopic sinus surgery (ESS) through the comparison of quality of life measures in female and male patients who undergo surgical treatment for chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective observational cohort study. METHODS: Patients with CRS completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and EuroQol 5-Dimension Survey (EQ-5D) preoperatively and annually for 5 years following ESS. Health utility values (HUV) were calculated from EQ-5D scores. Comparisons of cohort characteristics were performed with chi-square and t-tests. A multivariable linear mixed effects model evaluated changes in SNOT-22 and HUV over time by gender. RESULTS: Among the 1268 patients (54% female) enrolled, 789 and 343 completed postoperative surveys at one and 5 years, respectively. Preoperatively, females experienced more severe symptoms: mean SNOT-22 score (51.1 ± 20.9 female vs. 44.7 ± 20.0 male, p < 0.001) and HUV (0.80 ± 0.14 female vs. 0.84 ± 0.11 male, p < 0.001). These gender differences were resolved by year one postoperatively (SNOT-22: p = 0.083; HUV: p = 0.465). Two years after surgery, however, females reported more severe symptoms (SNOT-22: 25.6 ± 20.7 female vs. 21.5 ± 17.4 male, p = 0.005; HUV: 0.88 ± 0.12 female vs. 0.90 ± 0.11 male, p = 0.018), a difference that persisted at year five. These gender-related differences remained after adjusting for age, race, ethnicity, nasal polyps, history of prior ESS, and smoking status (p < 0.001). Within-subject improvement was comparable between genders (SNOT-22: p = 0.869; HUV: p = 0.611). CONCLUSION: Females with CRS reported more severe symptoms both before and 5 years after surgery compared to their male counterparts. Understanding the mechanism behind these gender-related differences is important for optimizing CRS treatment. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3319-3326, 2023.


Assuntos
Rinite , Sinusite , Humanos , Masculino , Feminino , Qualidade de Vida , Estudos Prospectivos , Rinite/cirurgia , Sinusite/cirurgia , Doença Crônica , Endoscopia/métodos , Resultado do Tratamento
20.
Ann Otol Rhinol Laryngol ; 132(12): 1682-1685, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37329265

RESUMO

BACKGROUND: Clinicians are increasingly adopting telemedicine in an effort to expand patient access and efficiently deliver care. The degree of health disparities among patients receiving otolaryngologic telemedical care is unclear. AIMS: We performed a retrospective cross-sectional study to explore disparities in telemedicine delivery. METHODS: We evaluated otolaryngology clinical visits from January 2019 to November 2022. We obtained patient demographics and visit characteristics (e.g., subspecialty, telemedicine vs in-person). Our primary outcome was demographic characteristics of otolaryngology patients who received telemedicine vs in-person care during the study timeframe. RESULTS: A total of 231,384 otolaryngology clinical visits were reviewed, of which 26,895 (11.6%) were telemedicine visits. Rhinology (36.5%) and facial plastics (28.4%) subspecialties performed the most telemedicine visits. On multivariate analysis, individuals who identified as Asian, non-English speaking, and with Medicare insurance were statistically significantly less likely to use telemedicine than in-person services. CONCLUSION: Our findings suggest that expanding telemedicine care may not improve access for all populations, and socioeconomic factors are important considerations to ensure patients are receiving equally accessible care. Futures studies are warranted to understand how these disparities may impact health outcomes and patient satisfaction with care.


Assuntos
Otolaringologia , Telemedicina , Estados Unidos , Humanos , Idoso , Estudos Transversais , Medicare , Estudos Retrospectivos
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