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1.
Cochlear Implants Int ; 24(5): 273-281, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37489512

RESUMO

OBJECTIVE: To investigate whether revision surgery with the same device results in a change in three key indicators of electrode positioning: scalar location, mean modiolar distance (M¯), and angular insertion depth (AID). METHODS: Retrospective analysis of a cochlear implant database at a university-based tertiary medical center. Intra-operative CT scans were obtained after initial and revision implantation. Electrode array (EA) position was calculated using auto-segmentation techniques. Initial and revision scalar location, M¯, and AID were compared. RESULTS: Mean change in M¯ for all ears was -0.07 mm (SD 0.24 mm; P = 0.16). The mean change in AID for all ears was -5° (SD 67°; P = 0.72). Three initial implantations with pre-curved EAs resulted in a translocation from Scala Tympani (ST) to Scala Vestibuli (SV). Two remained translocated after revision, while one was corrected when revised with a straight EA. An additional five translocations occurred after revision. CONCLUSIONS: In this study examining revision cochlear implantation from a single manufacturer, we demonstrated no significant change in key indicators of EA positioning, even when revising with a different style of electrode. However, the revision EA is not necessarily confined by the initial trajectory and there may be an increased risk of translocation.


Assuntos
Implante Coclear , Implantes Cocleares , Humanos , Estudos Retrospectivos , Cóclea , Reimplante
2.
Ear Nose Throat J ; 102(11): 739-741, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34218707

RESUMO

When in-person experiences were taken away from medical students and residency applicants during the COVID-19 pandemic, institutions had to pivot to virtual experiences. We present here a comprehensive overview of virtual engagement for medical students. As we increasingly embrace virtual opportunities, it may be possible to continue utilizing these programs for many years to come.


Assuntos
COVID-19 , Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Pandemias
3.
J Neurosurg Pediatr ; 31(2): 179-185, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36401542

RESUMO

OBJECTIVE: Patients with fibrous dysplasia (FD) of the anterior skull base can experience progressive visual loss and impairment. The authors reviewed their experience with endonasal decompression of the optic nerve (ON) in this patient population. Endoscopic ON decompression (EOND) is a feasible surgical approach for children with FD and visual deficit due to structural ON compression. METHODS: Electronic medical records of children between 1 and 17 years of age with unilateral FD of the anterior skull base and concomitant ON compression, who required EOND between 2017 and 2022 (n = 4), were reviewed for demographic data, both pre- and postoperative imaging, and evaluations by an otolaryngologist, neurosurgeon, and ophthalmologist in a multidisciplinary fashion. RESULTS: EOND was found to be a safe and effective surgery for children with FD. Visual acuity was stable in 80% of the eyes postoperatively. Visual fields improved in 40% of the eyes and remained stable in the rest. CONCLUSIONS: EOND is beneficial for progressive optic neuropathy that is unresponsive to steroid therapy and can prevent permanent disability if performed prior to irreversible damage to the nerve. EOND can decompress the edematous ON with proper exposure of the optic canal and orbital apex, without any major complications.


Assuntos
Doenças do Nervo Óptico , Órbita , Humanos , Criança , Doenças do Nervo Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/cirurgia , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/cirurgia , Endoscopia/métodos , Descompressão Cirúrgica/métodos , Resultado do Tratamento
4.
J Craniofac Surg ; 33(8): 2659-2664, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36217234

RESUMO

INTRODUCTION: The temporoparietal fascial (TPF) and occipital cranial fascial (OCP) flaps are the mainstay of implant coverage in alloplastic auricular reconstruction. Their optimal design is critical for elevating a robust flap that ultimately leads to favorable outcomes. MATERIALS AND METHODS: Sixteen TPF and OCP dissections were performed on 8 cadaveric specimens. Vascular anatomy and key landmarks were documented. The minimum flap size that incorporated ideal vasculature and would appropriately cover a porous polyethylene implant was measured. RESULTS: The minimum flap dimensions (length × width × base width) to cover a standard PPE auricular implants were on average 11×8.3×6.4 cm for TPF and 13.1×8.6×6.5 cm for OCP. The average axial length of the superficial temporal artery and occipital artery were 12.51 and 13.2 cm, respectively. An "occipital elbow" was located on average 8.2 cm posterior to the external acoustic canal. The postauricular fascia contained additional contributions from the occipital artery and mastoid emissary vein, which was located on average 5.9 cm posterior to the superficial temporal artery. CONCLUSIONS: This study highlights the anatomic features behind optimal TPF and OCP flap design for auricular reconstruction. Contributions to axial length and anatomic relationships of their primary arterial supply, significance of the occipital elbow as a reliable landmark for fascial dissection, and importance of the postauricular fascia and its vascular supply for flap viability are emphasized. Ultimately, the authors provide minimal dimensions for both TPF and OCP flaps to obtain adequate alloplastic implant coverage.


Assuntos
Implantes Dentários , Humanos , Retalhos Cirúrgicos/irrigação sanguínea , Fáscia , Artérias Temporais/cirurgia , Polietileno
5.
Otolaryngol Head Neck Surg ; 166(2): 274-281, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34030493

RESUMO

OBJECTIVE: To evaluate the associations between median household income (MHI) and area deprivation index (ADI) on postoperative outcomes in oral cavity cancer. STUDY DESIGN: Retrospective review (2000-2019). SETTING: Single-institution tertiary medical center. METHODS: MHI and ADI were matched from home zip codes. Main postoperative outcomes of interest were length of tracheostomy use, length of hospital stay, return to oral intake, discharge disposition, and 60-day readmissions. Linear and logistic regression controlled for age, sex, race, body mass index, tobacco and alcohol use history, primary tumor location, disease staging at presentation, and length of surgery. A secondary outcome was clinical disease staging (I-IV) at time of presentation. RESULTS: The cohort (N = 681) was 91.3% White and 38.0% female, and 51.7% presented with stage IV disease. The median age at the time of surgery was 62 years (interquartile range [IQR], 53-71). The median MHI was $47,659 (IQR, $39,324-$58,917), and the median ADI was 67 (IQR, 48-79). ADI and MHI were independently associated with time to return of oral intake (ß = 0.130, P = .022; ß = -0.092, P = .045, respectively). Neither was associated with length of tracheostomy, hospital stay, discharge disposition, or readmissions. MHI quartiles were associated with a lower risk of presenting with more advanced disease (Q3 vs Q1: adjusted odds ratio, 0.56 [95% CI, 0.32-0.97]). CONCLUSION: MHI is associated with oral cavity cancer staging at the time of presentation. MHI and ADI are independently associated with postoperative return to oral intake following intraoral tumor resection and free flap reconstruction.


Assuntos
Retalhos de Tecido Biológico , Renda/estatística & dados numéricos , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Bucais , Procedimentos de Cirurgia Plástica , Áreas de Pobreza , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
6.
Otolaryngol Head Neck Surg ; 166(3): 454-460, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34399644

RESUMO

OBJECTIVE: To determine the preoperative risk factors most predictive of prolonged length of stay (LOS) or admission to a skilled nursing facility (SNF) or inpatient rehabilitation center (IPR) after free flap reconstruction of the head and neck. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. METHODS: Retrospective review of 1008 patients who underwent tumor resection and free flap reconstruction of the head and neck at a tertiary referral center from 2002 to 2019. RESULTS: Of 1008 patients (65.7% male; mean age of 61.4 years, SD 14.0 years), 161 (15.6%) were discharged to SNF/IPR, and the median LOS was 7 days. In multiple linear regression analysis, Charlson Comorbidity Index (CCI; P < .001), American Society of Anesthesiologists (ASA) classification (P = .021), female gender (P = .023), and inability to tolerate oral diet preoperatively (P = .006) were statistically significantly related to increased LOS, whereas age, body mass index (BMI), modified frailty index (MFI), a history of prior radiation or chemotherapy, and home oxygen use were not. Multiple logistic regression analysis demonstrated that CCI (odds ratio [OR] = 1.119, confidence interval [CI] 1.023-1.223), age (OR = 1.082, CI 1.056-1.108), and BMI <19.0 (OR = 2.141, CI 1.159-3.807) were the only variables statistically significantly related to posthospital placement in an SNF or IPR. CONCLUSION: Common tools for assessing frailty and need for additional care may be inadequate in a head and neck reconstructive population. CCI appears to be the best of the aggregate metrics assessed, with significant relationships to both LOS and placement in SNF/IPR.


Assuntos
Fragilidade , Retalhos de Tecido Biológico , Feminino , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
7.
J Neurol Surg B Skull Base ; 82(Suppl 3): e70-e78, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34306919

RESUMO

Background Pituitary apoplexy is often treated urgently, but this is based on studies which assess vision categorically and dichotomizes the time interval between symptom onset and surgery which may introduce bias in measuring an association between the two. Objective This study was aimed to assess for a relationship between continuously valued surgery delay and visual acuity recovery after pituitary apoplexy. Methods In this retrospective study, all patients presenting with symptomatic pituitary apoplexy between 2004 and 2016 were identified from an institutional database. The primary endpoint was visual acuity improvement, measured as the difference in acuity from the pre- to postoperative period, and measured in Logarithm of the Minimal Angle of Resolution (LogMAR) units. Analysis was performed using continuous values of time delay and visual acuity to assess for an underlying association. Results Thirty-two pituitary apoplexy patients were identified. Visual acuity deficits were reported in 81%. The median visual acuity was 0.35 LogMAR (Snellen's fraction 20/40) preoperatively, and 0.1 (20/25) postoperatively ( p < 0.01). The time between symptom onset and surgery was not associated with improvement in visual acuity ( p = 0.46). When the time delay and visual outcome were intentionally dichotomized, patients undergoing surgery within 2 days of symptom onset had 0.21 times the odds of a good visual outcome (95% confidence interval [CI]: 0.04-1.05). Conclusion When assessed as continuously valued measures, the time from symptom onset to surgical intervention and the improvement in visual acuity are not associated, although intentional dichotomization of data produced conflicting results.

8.
Laryngoscope ; 130(2): E57-E64, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30883777

RESUMO

OBJECTIVES: Bilateral vocal fold immobility (BVFI) is a rare and life-threatening condition in which both vocal folds are fixed, resulting in airway obstruction associated with life-threatening respiratory compromise. Treatment of BVFI is largely surgical and remains an unsatisfactory compromise between voice, breathing, and swallowing. No comparisons between currently employed techniques currently exist. We sought to employ computational fluid dynamics (CFD) modeling to delineate the optimal surgical approach for BVFI. METHODS: Utilizing clinical computed tomography of BVFI subjects, coupled with image analytics employing CFD models and subject pulmonary function data, we compared the airflow features in the baseline pathologic states and changes seen between endoscopic cordotomy, endoscopic suture lateralization, and posterior cricoid expansion. RESULTS: CFD modeling demonstrated that the greatest airflow velocity occurs through the posterior glottis on inspiration and anterior glottis on expiration in both the normal condition and in BVFI. Glottic airflow velocity and resistance were significantly higher in the BVFI condition compared to normal. Geometric indices (cross-sectional area of airway) were lower in posterior cricoid expansion surgery when compared to alternate surgical approaches. CFD measures (airflow velocity and resistance) improved with all surgical approaches but were superior with posterior cricoid expansion. CONCLUSION: CFD modeling can provide discrete, quantitative assessment of the airflow through the laryngeal inlet, and offers insights into the pathophysiology and changes that occur after surgery for BVFI. LEVEL OF EVIDENCE: NA. Laryngoscope, 130:E57-E64, 2020.


Assuntos
Simulação por Computador , Hidrodinâmica , Paralisia das Pregas Vocais/fisiopatologia , Paralisia das Pregas Vocais/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Paralisia das Pregas Vocais/diagnóstico por imagem
9.
J Neurosurg ; 131(1): 304-310, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771763

RESUMO

On May 5, 1961, Alan B. Shepard Jr. piloted the Freedom 7 craft into a suborbital flight to become the first American man in space. His promising astronautical career was soon scuttled by spells of dizziness and tinnitus later diagnosed as Ménière's disease, until William F. House-considered the father of neurotology and a pioneer in surgery for vestibular schwannomas-intervened. In 1968 House implanted an endolymphatic-subarachnoid shunt, which at the time was a virtually experimental procedure. Shepard's debilitating Ménière's disease was cured, but not quite in time for him to pilot the doomed Apollo 13 mission; he was reassigned to Apollo 14 and as a result would step foot on the moon on February 5, 1971. This historical vignette depicts the tale of how the career trajectories of Shepard and House-two notable figures in their respective fields-fatefully intersected.

10.
Med Sci Educ ; 29(4): 1033-1042, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34457581

RESUMO

Vanderbilt University School of Medicine recently changed from 2 pre-clerkship years (Traditional curriculum) to a 1.5-year pre-clerkship phase for one class (Hybrid curriculum) to a 1-year pre-clerkship phase (Curriculum 2.0). This study investigated the relationship between shortened pre-clerkship training and stress associated with selecting a residency field. The surveyed graduating medical student population included one cohort from the Traditional and Hybrid curricula, and the first two cohorts from Curriculum 2.0. The authors modeled recollected stress levels using a Zero-Inflated Linear Mixed Model with additional covariate and random effects adjustments. Specialty decision-related stress levels increased in the Hybrid curriculum by 10.208 points [p = 0.0115, 95% CI 2.293, 18.122] on a 0-100 point scale. Curriculum 2.0 students had an insignificant increase in stress of 4.062 points [p = 0.304, 95% CI - 3.690, 11.814] relative to the Traditional curriculum. Time since starting medical school and time when a specialty was chosen were the largest factors associated with stress. While this study only evaluated a single facet of the potential downstream effects of curricular change, these data should inspire confidence for reform efforts as a significant increase in specialty decision-related stress present in Hybrid curriculum resolved in both cohorts of Curriculum 2.0.

11.
Adv Healthc Mater ; 6(22)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28892261

RESUMO

3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the <100 micrometer-scale trabecular architecture essential for investigating the cellular response to the morphometric properties of bone. In this study, it is hypothesized that the architecture of trabecular bone regulates osteoblast differentiation and mineralization. To test this hypothesis, human bone-templated 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function.


Assuntos
Osso Esponjoso/citologia , Materiais Biocompatíveis/química , Regeneração Óssea/fisiologia , Cartilagem/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Teste de Materiais/métodos , Células-Tronco Mesenquimais/citologia , Osteogênese/fisiologia , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/química
13.
Int J Pediatr Otorhinolaryngol ; 84: 52-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27063753

RESUMO

Cervicofacial segmental infantile hemangiomas (IH) may result in airway obstruction requiring use of propranolol to induce hemangioma regression and reestablish the airway. We present the first case using intravenous (IV) propranolol for control of airway obstruction and rapid expansion of cervicofacial IH in the setting of necrotizing enterocolitis (NEC) impaired gastrointestinal function. Intravenous dosing of propranolol was tolerated well in a critically ill neonate with multisystem complications of prematurity.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Hemangioma Capilar/tratamento farmacológico , Doenças do Prematuro/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Propranolol/uso terapêutico , Estado Terminal , Enterocolite Necrosante/complicações , Feminino , Hemangioma Capilar/complicações , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Injeções Intravenosas , Neoplasias Bucais/complicações
14.
Otolaryngol Head Neck Surg ; 155(2): 312-6, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26980904

RESUMO

Cochlear implantation in canal wall down mastoid (CWD) cavities is fraught with the issue of how best to manage the mastoid cavity. Decision points include whether the external auditory meatus should be overclosed, whether the implantation should be staged, or even if the eustachian tube should be plugged. Given these options, we sought to describe our experience of cochlear implantation in CWD cavities. Among evaluation of subjects ≥18 years of age, 9 had cochlear implants placed in CWD mastoid cavities, 7 of which had the external auditory meatus overclosed, while 2 maintained open cavities following implantation. With an average follow-up of 36.7 months (median, 22.8 months), 2 subjects who had overclosure developed meatal dehiscences requiring further intervention, while no complications were observed in the 2 patients who maintained open cavities.


Assuntos
Implante Coclear/métodos , Implantes Cocleares , Processo Mastoide/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Pain ; 154(12): 2853-2859, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23994450

RESUMO

G-protein coupled inwardly rectifying potassium (GIRK) channels are effectors determining degree of analgesia experienced upon opioid receptor activation by endogenous and exogenous opioids. The impact of GIRK-related genetic variation on human pain responses has received little research attention. We used a tag single nucleotide polymorphism (SNP) approach to comprehensively examine pain-related effects of KCNJ3 (GIRK1) and KCNJ6 (GIRK2) gene variation. Forty-one KCNJ3 and 69 KCNJ6 tag SNPs were selected, capturing the known variability in each gene. The primary sample included 311 white patients undergoing total knee arthroplasty in whom postsurgical oral opioid analgesic medication order data were available. Primary sample findings were then replicated in an independent white sample of 63 healthy pain-free individuals and 75 individuals with chronic low back pain (CLBP) who provided data regarding laboratory acute pain responsiveness (ischemic task) and chronic pain intensity and unpleasantness (CLBP only). Univariate quantitative trait analyses in the primary sample revealed that 8 KCNJ6 SNPs were significantly associated with the medication order phenotype (P < .05); overall effects of the KCNJ6 gene (gene set-based analysis) just failed to reach significance (P = .054). No significant KCNJ3 effects were observed. A continuous GIRK Related Risk Score (GRRS) was derived in the primary sample to summarize each individual's number of KCNJ6 "pain risk" alleles. This GRRS was applied to the replication sample, which revealed significant associations (P < .05) between higher GRRS values and lower acute pain tolerance and higher CLBP intensity and unpleasantness. Results suggest further exploration of the impact of KCNJ6 genetic variation on pain outcomes is warranted.


Assuntos
Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Dor/diagnóstico , Dor/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Feminino , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Adulto Jovem
16.
PLoS One ; 6(10): e23666, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21984891

RESUMO

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.


Assuntos
Aptidão , Progressão da Doença , Educação de Graduação em Medicina , Avaliação Educacional , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/patologia , Estudantes , Humanos , Prontuários Médicos , Estações do Ano , Índice de Gravidade de Doença
17.
J Biol Chem ; 285(50): 38987-9000, 2010 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-20861012

RESUMO

ID2 is a rhythmically expressed HLH transcriptional repressor. Deletion of Id2 in mice results in circadian phenotypes, highlighted by disrupted locomotor activity rhythms and an enhanced photoentrainment response. ID2 can suppress the transactivation potential of the positive elements of the clock, CLOCK-BMAL1, on mPer1 and clock-controlled gene (CCG) activity. Misregulation of CCGs is observed in Id2(-/-) liver, and mutant mice exhibit associated alterations in lipid homeostasis. These data suggest that ID2 contributes to both input and output components of the clock and that this may be via interaction with the bHLH clock proteins CLOCK and BMAL1. The aim of the present study was to explore this potential interaction. Coimmunoprecipitation analysis revealed the capability of ID2 to complex with both CLOCK and BMAL1, and mammalian two-hybrid analysis revealed direct interactions of ID2, ID1 and ID3 with CLOCK and BMAL1. Deletion of the ID2 HLH domain rendered ID2 ineffective at inhibiting CLOCK-BMAL1 transactivation, suggesting that interaction between the proteins is via the HLH region. Immunofluorescence analysis revealed overlapping localization of ID2 with CLOCK and BMAL1 in the cytoplasm. Overexpression of CLOCK and BMAL1 in the presence of ID2 resulted in a significant reduction in their nuclear localization, revealing that ID2 can sequester CLOCK and BMAL1 to the cytoplasm. Serum stimulation of Id2(-/-) mouse embryonic fibroblasts resulted in an enhanced induction of mPer1 expression. These data provide the basis for a molecular mechanism through which ID2 could regulate aspects of both clock input and output through a time-of-day specific interaction with CLOCK and BMAL1.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Proteínas CLOCK/metabolismo , Regulação da Expressão Gênica , Proteína 2 Inibidora de Diferenciação/metabolismo , Proteínas Circadianas Period/metabolismo , Animais , Citoplasma/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Técnicas do Sistema de Duplo-Híbrido
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